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Yasmin F, Sutradhar S, Roy A, Mukherjee S. Effects of dietary quality on melatonin in gut, serum and ovary in mediating growth, digestive and ovarian physiology in juvenile carp (Catla catla). Gen Comp Endocrinol 2025; 369:114752. [PMID: 40388990 DOI: 10.1016/j.ygcen.2025.114752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Revised: 05/16/2025] [Accepted: 05/16/2025] [Indexed: 05/21/2025]
Abstract
The dietary protein and tryptophan of fish feed have vital roles in the growth performance, stress management, and digestive physiology of fish. However, in this context, the functions of gut melatonin, which depend on the availability of food, the timing of food supply, the frequency of feeds/day, the quality of food, and the growth stages of carp, still need to be clarified. Hence, the present study aimed to investigate the impact of dietary quality on specific growth rate (SGR), residual gut content (RGC), feeding intensity (FI), gut melatonin, gut oxidative stress and its major antioxidants, vital digestive enzymes in juvenile carp, Catla catla (mean body weight: 274 ± 16.63 g). Besides, serum melatonin and ovarian melatonin, gonado-somatic index (GSI), and different growth stages of oocytes were also assessed before the estimation of oxidative stress and major antioxidant enzymes in the ovary. The fish were fed four diets viz. (i) a standard diet (SD/control) (with 34.99 % protein, 14.56 % carbohydrate, 9.84 % oil, and 0.36 % L-tryptophan) (ii) one protein (PRD with 41.02 % protein and 0.46 % L-tryptophan), (iii) two L-tryptophan (TrpRD1 with 0.96 %, and TrpRD2 with 1.36 % tryptophan), -rich diets for 30 days. The SGR was higher only in PRD, but feeding was reduced in PRD and TrpRDs compared to SD-fed carp. However, the PRD and TrpRDs stimulated gut melatonin, digestive enzymes and all the studied antioxidants with reduced oxidative stress by lowering malondialdehyde (MDA). Moreover, a parallel increase in serum melatonin and ovarian melatonin with gut melatonin has been noticed in both the PRD and TrpRDs. All these experimental diets showed pro-gonadal effects by increasing stage-I oocytes and by reducing oxidative stress in the developing ovary in juvenile carp, compared to SD-fed carp. This opens avenues for future research on the role of feed-induced gut melatonin in fish nutrition and reproduction.
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Affiliation(s)
- Farha Yasmin
- Fish Biology and Endocrinology Laboratory, Department of Zoology, University of North Bengal, Siliguri 734013, India
| | - Sona Sutradhar
- Fish Biology and Endocrinology Laboratory, Department of Zoology, University of North Bengal, Siliguri 734013, India
| | - Arun Roy
- Fish Biology and Endocrinology Laboratory, Department of Zoology, University of North Bengal, Siliguri 734013, India
| | - Sourav Mukherjee
- Fish Biology and Endocrinology Laboratory, Department of Zoology, University of North Bengal, Siliguri 734013, India.
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Niu T, Ding Z, Zeng J, Yan Z, Duan H, Lv J, Zhang Y, Zhang L, Hu J. Melatonin Sources in Sheep Rumen and Its Role in Reproductive Physiology. Animals (Basel) 2024; 14:3451. [PMID: 39682413 DOI: 10.3390/ani14233451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 08/30/2024] [Accepted: 09/04/2024] [Indexed: 12/18/2024] Open
Abstract
In mammals, the melatonin (Mel) concentration in the gastrointestinal tract is 400 times greater than in the pineal gland. However, the origin of Mel in the gastrointestinal tract and its role in reproductive regulation remains unclear. Therefore, we analyzed three potential Mel sources (feed, microorganisms, and the rumen wall) for their contribution to high Mel levels in the rumen and their biological effects. The feed contained high Mel concentrations, and Mel in rumen fluid and blood peaked two hours after feeding. Rumen microbial analysis showed a strong positive correlation between Mel and specific microbes, including Megasphaera, Butyrivibrio, Acetobacter, and Olsenella. In vitro experiments indicated that rumen microorganisms synthesized Mel from tryptophan. The rumen wall also contains key enzymes, AANAT and HIOMT, which catalyze Mel synthesis and membrane receptors MT1 and MT2 that mediate the function of Mel, suggesting that the rumen wall synthesizes Mel. Mel peaked in both rumen fluid and blood two hours after feeding. Feeding also altered blood levels of Mel, Gonadotropin-releasing hormone (GnRH), Luteinizing hormone (LH), Follicle-stimulating hormone (FSH), progesterone (P4), and Estradiol (E2), with a correlation between Mel and fluctuations in GnRH, LH, P4, and E2 levels. Our findings suggest that feed is the primary source of high Mel levels in the rumen and impacts reproductive hormone fluctuations. This study elucidates the origin of high rumen Mel concentrations and reveals that food intake affects the natural secretion of various hormones, offering a new perspective on food sources for regulating reproductive physiology.
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Affiliation(s)
- Tian Niu
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
| | - Ziqiang Ding
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China
| | - Jianlin Zeng
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
| | - Zhenxing Yan
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
| | - Hongwei Duan
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
| | - Jianshu Lv
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
| | - Yong Zhang
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
| | - Lihong Zhang
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
| | - Junjie Hu
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
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Zimmermann P, Kurth S, Pugin B, Bokulich NA. Microbial melatonin metabolism in the human intestine as a therapeutic target for dysbiosis and rhythm disorders. NPJ Biofilms Microbiomes 2024; 10:139. [PMID: 39604427 PMCID: PMC11603051 DOI: 10.1038/s41522-024-00605-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Accepted: 11/10/2024] [Indexed: 11/29/2024] Open
Abstract
Melatonin (MT) (N-acetyl-5-methoxytryptamine) is an indoleamine recognized primarily for its crucial role in regulating sleep through circadian rhythm modulation in humans and animals. Beyond its association with the pineal gland, it is synthesized in various tissues, functioning as a hormone, tissue factor, autocoid, paracoid, and antioxidant, impacting multiple organ systems, including the gut-brain axis. However, the mechanisms of extra-pineal MT production and its role in microbiota-host interactions remain less understood. This review provides a comprehensive overview of MT, including its production, actions sites, metabolic pathways, and implications for human health. The gastrointestinal tract is highlighted as an additional source of MT, with an examination of its effects on the intestinal microbiota. This review explores whether the microbiota contributes to MT in the intestine, its relationship to food intake, and the implications for human health. Due to its impacts on the intestinal microbiota, MT may be a valuable therapeutic agent for various dysbiosis-associated conditions. Moreover, due to its influence on intestinal MT levels, the microbiota may be a possible therapeutic target for treating health disorders related to circadian rhythm dysregulation.
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Affiliation(s)
- Petra Zimmermann
- Department of Community Health, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
- Department of Paediatrics, Fribourg Hospital, Fribourg, Switzerland.
- Infectious Diseases Research Group, Murdoch Children's Research Institute, Parkville, VIC, Australia.
- Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia.
| | - Salome Kurth
- Department of Psychology, University of Fribourg, Fribourg, Switzerland
| | - Benoit Pugin
- Laboratory of Food Systems Biotechnology, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
| | - Nicholas A Bokulich
- Laboratory of Food Systems Biotechnology, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
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Ogundare W, Teeple K, Fisher E, Davis C, Reis LG, Jannasch A, Beckett LM, Schinckel A, Minor R, Casey T. Cooling lactating sows exposed to early summer heat wave alters circadian patterns of behavior and rhythms of respiration, rectal temperature, and saliva melatonin. PLoS One 2024; 19:e0310787. [PMID: 39480888 PMCID: PMC11527313 DOI: 10.1371/journal.pone.0310787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 07/30/2024] [Indexed: 11/02/2024] Open
Abstract
Heat stress (HS) exerts detrimental effects on animal production, with lactating sows being particularly vulnerable. Understanding the mechanisms involved in HS response could aid in developing effective strategies against the negative impacts on livestock. Recent genome wide association studies identified two core circadian clock genes as potential candidates in mediating HS response. The study aimed to investigate how cooling lactating sows under natural heat stress conditions impacted circadian patterns of respiration rate (RR), rectal temperature (RT), behavior, salivary melatonin and cortisol levels, and diurnal patterns of cytokines in saliva. Mixed parity lactating sows were assigned to one of two treatment groups: electronic cooling pad (C; n = 9) and heat-stressed (H; n = 9). The experiment spanned two 48 h periods of elevated ambient temperatures due to summer heat wave. In the first 48 h period, RR was recorded every 30 min, RT every 60 min, and behaviors (eating, standing, sitting, laying, sleeping, drinking, and nursing) every 5 min. In the second 48 h period, saliva samples were collected every 4 h. Cooling reduced RR and RT and altered circadian patterns (P < 0.05). Cooling did not affect amount of time engaged in any behavior over the 48 h period (P > 0.05), however, daily patterns of eating, standing and laying differed between the treatments (P < 0.05), with altered eating behavior related to RT increment in H sows (P < 0.05). Cooling increased and altered the circadian pattern of salivary melatonin (P < 0.05). Cooling also influenced the diurnal pattern of saliva cytokines. Cooling had no impact on saliva cortisol levels. In conclusion, cooling HS sows impacted circadian rhythms of physiology and behavior, supporting the need for further research to understand if circadian disruption underlies decreased production efficiency of HS animals.
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Affiliation(s)
- Wonders Ogundare
- Department of Animal Sciences, North Carolina Agricultural and Technical State University, Greensboro, North Carolina, United States of America
| | - Kelsey Teeple
- Department of Animal Sciences, Purdue University, West Lafayette, Indiana, United States of America
| | - Elizabeth Fisher
- Department of Animal Sciences, Purdue University, West Lafayette, Indiana, United States of America
| | - Corrin Davis
- Department of Animal Sciences, Purdue University, West Lafayette, Indiana, United States of America
| | - Leriana Garcia Reis
- Department of Animal Sciences, Purdue University, West Lafayette, Indiana, United States of America
| | - Amber Jannasch
- Metabolite Profiling Facility, Bindley Bioscience Center, Purdue University, West Lafayette, IN, United States of America
| | - Linda M. Beckett
- Department of Animal Sciences, Purdue University, West Lafayette, Indiana, United States of America
| | - Allan Schinckel
- Department of Animal Sciences, Purdue University, West Lafayette, Indiana, United States of America
| | - Radiah Minor
- Department of Animal Sciences, North Carolina Agricultural and Technical State University, Greensboro, North Carolina, United States of America
| | - Theresa Casey
- Department of Animal Sciences, Purdue University, West Lafayette, Indiana, United States of America
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Giezenaar C, Montoya CA, Kreutz K, Hodgkinson S, Roy NC, Mace LJ, Fraser K, Fernstrom JD, McNabb WC, Moughan PJ. Effects of Different Protein Sources on Amino Acid Absorption and Plasma Appearance of Tryptophan, Large Neutral Amino Acids, and Tryptophan Metabolites in Pigs. J Nutr 2024; 154:2948-2962. [PMID: 39019158 DOI: 10.1016/j.tjnut.2024.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 06/21/2024] [Accepted: 07/08/2024] [Indexed: 07/19/2024] Open
Abstract
BACKGROUND Absorption of tryptophan (TRP) across the gut epithelium is potentially modulated by competing large neutral amino acids (LNAAs), which could affect the appearance of TRP and its metabolites in the bloodstream. OBJECTIVES This study aimed to determine, in a growing pig model of an adult human, the absorption of TRP and other LNAAs from the gastrointestinal tract, and plasma appearance of TRP, LNAAs, and TRP metabolites, in response to dietary proteins varying in TRP content. METHODS Pigs were adapted for 7 d to each of 4 diets that differed in their protein source and TRP content: 1) alpha-lactalbumin (AL; 9.95 mg TRP/g diet DM), 2) whey protein (6.59 mg TRP/g), 3) casein (3.73 mg TRP/g), or 4) zein (0.14 mg TRP/g). On day 8, pigs were euthanised after a 12-h fast (baseline), or 1, 2, 3, 4, or 6 h after they received a test meal consisting of 45 g protein, or a protein-free meal (n = 6 pigs at each time in each meal group). Tryptophan and LNAA absorption from the small intestine, and appearance of TRP, LNAAs, and TRP metabolites (melatonin, serotonin, kynurenine pathway metabolites), in the portal vein and systemic circulation, were determined. RESULTS AL intake resulted in sustained elevated plasma TRP concentrations after an overnight fast. The amount of TRP absorbed was dose-dependently related to protein TRP content (P = 0.028), with fastest rates for pigs fed AL (371 mg/h). Portal and systemic plasma TRP, TRP/LNAA, and the TRP metabolites were highest (P ≤ 0.05) after AL intake, and remained above baseline levels for ∼4 h postprandially. Absorption rates of TRP correlated with postprandial plasma TRP and TRP metabolites (P ≤ 0.05). CONCLUSIONS In adult humans, postprandial plasma TRP and TRP metabolite concentrations can likely be modulated by the TRP content of the meal.
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Affiliation(s)
- Caroline Giezenaar
- Riddet Institute, Massey University, Te Ohu Rangahau Kai Facility, Palmerston North, New Zealand; Food Experience and Sensory Testing (Feast) Laboratory, School of Food and Advanced Technology, Massey University, Palmerston North, New Zealand.
| | - Carlos A Montoya
- Riddet Institute, Massey University, Te Ohu Rangahau Kai Facility, Palmerston North, New Zealand; Smart Foods and Bioproducts, Te Ohu Rangahau Kai Facility, AgResearch Limited, Palmerston North, New Zealand
| | - Kevin Kreutz
- Riddet Institute, Massey University, Te Ohu Rangahau Kai Facility, Palmerston North, New Zealand
| | - Suzanne Hodgkinson
- Riddet Institute, Massey University, Te Ohu Rangahau Kai Facility, Palmerston North, New Zealand
| | - Nicole C Roy
- Riddet Institute, Massey University, Te Ohu Rangahau Kai Facility, Palmerston North, New Zealand; High-Value Nutrition National Science Challenge, Auckland, New Zealand; Department of Human Nutrition, University of Otago, Dunedin, New Zealand
| | - Louise J Mace
- Smart Foods and Bioproducts, Te Ohu Rangahau Kai Facility, AgResearch Limited, Palmerston North, New Zealand
| | - Karl Fraser
- Riddet Institute, Massey University, Te Ohu Rangahau Kai Facility, Palmerston North, New Zealand; High-Value Nutrition National Science Challenge, Auckland, New Zealand; Department of Human Nutrition, University of Otago, Dunedin, New Zealand
| | - John D Fernstrom
- Department of Psychiatry, and Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
| | - Warren C McNabb
- Riddet Institute, Massey University, Te Ohu Rangahau Kai Facility, Palmerston North, New Zealand; High-Value Nutrition National Science Challenge, Auckland, New Zealand
| | - Paul J Moughan
- Riddet Institute, Massey University, Te Ohu Rangahau Kai Facility, Palmerston North, New Zealand
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Kennaway DJ. The mammalian gastro-intestinal tract is a NOT a major extra-pineal source of melatonin. J Pineal Res 2023; 75:e12906. [PMID: 37649458 DOI: 10.1111/jpi.12906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Revised: 07/31/2023] [Accepted: 08/16/2023] [Indexed: 09/01/2023]
Abstract
In 1992, a paper reported that the melatonin content of the rat duodenum was 24 000 ± 2000 pg/g tissue (range: 4000-100 000 pg/g) while the pineal melatonin content was 580 000 ± 36 000 pg/g. The data has been used for the last 30 years to infer that the gut produces 400 hundred times more melatonin than the pineal gland and that it is the source of plasma melatonin during the daytime. No-one has ever challenged the statement. In this review, evidence is summarised from the literature that pinealectomy eliminates melatonin from the circulation and that studies to the contrary have relied upon poorly validated immunoassays that overstate the levels. Similarly studies that have reported increases in plasma melatonin following tryptophan administration failed to account for cross reactivity of tryptophan and its metabolites in immunoassays. The most extraordinary observation from the literature is that in those studies that have measured melatonin in the gut since 1992, the tissue content is vastly lower than the original report, even when the methodology used could be overestimating the melatonin content due to cross reactivity. Using the more contemporary results we can calculate that rather than a 400:1 ratio of duodenum: pineal melatonin, a ratio of 0.05-0.19: 1 is likely. The gut is not a major extra-pineal source of melatonin; indeed it may well not produce any.
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Affiliation(s)
- David J Kennaway
- Robinson Research Institute and Adelaide School of Medicine, University of Adelaide, Adelaide Health and Medical Science Building, North Terrace, Adelaide, South Australia, Australia
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Kwak MJ, Chae KS, Kim JN, Whang KY, Kim Y. Dietary effects of melatonin on growth performance by modulation of protein bioavailability and behavior in early weaned rats and pigs. JOURNAL OF ANIMAL SCIENCE AND TECHNOLOGY 2023; 65:1053-1064. [PMID: 37969335 PMCID: PMC10640933 DOI: 10.5187/jast.2023.e44] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 05/03/2023] [Accepted: 05/04/2023] [Indexed: 11/17/2023]
Abstract
Melatonin, which is produced from tryptophan, exerts various biological functions, including the regulation of circadian rhythm, sedative agents, and antioxidant ability. Therefore, we conducted two experiments with early-weaned rats and pigs to investigate the antioxidant and sedative effects of melatonin. In the rat experiment, a total of 42 rats (21 days old) were used, and the antioxidant capacity was determined. Next, we used 120 early-weaned piglets (21 days old) to conduct a 5-week experiment to evaluate the reductive effect of melatonin on energy-wasting movement, including roaming and fight states. Dietary melatonin supplementation significantly improved growth in both rats and pigs compared to the control groups. Additionally, rats fed a melatonin-supplemented diet showed advanced antioxidant capacity with a decrease in hepatic malondialdehyde concentration compared to rats fed a basal diet. Moreover, dietary melatonin ingestion increased resting and feeding behaviors and reduced roaming and fight behaviors during Days 8-21 compared to the control diet group. Collectively, early weaned animals given dietary melatonin supplementation showed improved growth through upregulation of hepatic antioxidant capacity and minimization of energy-wasting behavior, including roaming and fight states, after pigs' social hierarchy establishment.
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Affiliation(s)
- Min-Jin Kwak
- Department of Agricultural Biotechnology
and Research Institute of Agriculture and Life Science, Seoul National
University, Seoul 08826, Korea
| | - Kyeong Su Chae
- Division of Biotechnology, College of Life
Science and Biotechnology, Korea University, Seoul 02841,
Korea
| | - Jong Nam Kim
- Department of Food Science &
Nutrition, Dongseo University, Busan 47011, Korea
| | - Kwang-Youn Whang
- Division of Biotechnology, College of Life
Science and Biotechnology, Korea University, Seoul 02841,
Korea
| | - Younghoon Kim
- Department of Agricultural Biotechnology
and Research Institute of Agriculture and Life Science, Seoul National
University, Seoul 08826, Korea
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Yi X, Cai R, Shaoyong W, Wang G, Yan W, He Z, Li R, Chao M, Zhao T, Deng L, Yang G, Pang W. Melatonin promotes gut anti-oxidative status in perinatal rat by remodeling the gut microbiome. Redox Biol 2023; 65:102829. [PMID: 37527604 PMCID: PMC10407234 DOI: 10.1016/j.redox.2023.102829] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 07/25/2023] [Indexed: 08/03/2023] Open
Abstract
Gut health is important for nutrition absorption, reproduction, and lactation in perinatal and early weaned mammals. Although melatonin functions in maintaining circadian rhythms and preventing obesity, neurodegenerative diseases, and viral infections, its impact on the gut microbiome and its function in mediating gut health through gut microbiota remain largely unexplored. In the present study, the microbiome of rats was monitoring after fecal microbiota transplantation (FMT) and foster care (FC). The results showed that FMT and FC increased intestinal villus height/crypt depth in perinatal rats. Mechanistically, the melatonin-mediated remodeling of gut microbiota inhibited oxidative stress, which led to attenuation of autophagy and inflammation. In addition, FMT and FC encouraged the growth of more beneficial intestinal bacteria, such as Allobaculum, Bifidobacterium, and Faecalibaculum, which produce more short-chain fatty acids to strengthen intestinal anti-oxidation. These findings suggest that melatonin-treated gut microbiota increase the production of SCFAs, which improve gut health by reducing oxidative stress, autophagy and inflammation. The transfer of melatonin-treated gut microbiota may be a new and effective method by which to ameliorate gut health in perinatal and weaned mammals.
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Affiliation(s)
- Xudong Yi
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Rui Cai
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Weike Shaoyong
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Guoyan Wang
- Innovative Research Team of Animal Nutrition & Healthy Feeding, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Wenyong Yan
- Innovative Research Team of Animal Nutrition & Healthy Feeding, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Zhaozhao He
- Innovative Research Team of Animal Nutrition & Healthy Feeding, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Ri Li
- Innovative Research Team of Animal Nutrition & Healthy Feeding, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Mingkun Chao
- Innovative Research Team of Animal Nutrition & Healthy Feeding, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Tiantian Zhao
- Innovative Research Team of Animal Nutrition & Healthy Feeding, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Lu Deng
- Innovative Research Team of Animal Nutrition & Healthy Feeding, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
| | - Gongshe Yang
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
| | - Weijun Pang
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
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Horodincu L, Solcan C. Influence of Different Light Spectra on Melatonin Synthesis by the Pineal Gland and Influence on the Immune System in Chickens. Animals (Basel) 2023; 13:2095. [PMID: 37443893 DOI: 10.3390/ani13132095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 06/12/2023] [Accepted: 06/21/2023] [Indexed: 07/15/2023] Open
Abstract
It is well known that the pineal gland in birds influences behavioural and physiological functions, including those of the immune system. The purpose of this research is to examine the endocrine-immune correlations between melatonin and immune system activity. Through a description of the immune-pineal axis, we formulated the objective to determine and describe: the development of the pineal gland; how light influences secretory activity; and how melatonin influences the activity of primary and secondary lymphoid organs. The pineal gland has the ability to turn light information into an endocrine signal suitable for the immune system via the membrane receptors Mel1a, Mel1b, and Mel1c, as well as the nuclear receptors RORα, RORβ, and RORγ. We can state the following findings: green monochromatic light (560 nm) increased serum melatonin levels and promoted a stronger humoral and cellular immune response by proliferating B and T lymphocytes; the combination of green and blue monochromatic light (560-480 nm) ameliorated the inflammatory response and protected lymphoid organs from oxidative stress; and red monochromatic light (660 nm) maintained the inflammatory response and promoted the growth of pathogenic bacteria. Melatonin can be considered a potent antioxidant and immunomodulator and is a critical element in the coordination between external light stimulation and the body's internal response.
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Affiliation(s)
- Loredana Horodincu
- Preclinics Department, Faculty of Veterinary Medicine, "Ion Ionescu de la Brad" Iasi University of Life Sciences, Mihail Sadoveanu Alley, 700489 Iasi, Romania
| | - Carmen Solcan
- Preclinics Department, Faculty of Veterinary Medicine, "Ion Ionescu de la Brad" Iasi University of Life Sciences, Mihail Sadoveanu Alley, 700489 Iasi, Romania
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10
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Contreras-Correa ZE, Messman RD, Swanson RM, Lemley CO. Melatonin in Health and Disease: A Perspective for Livestock Production. Biomolecules 2023; 13:biom13030490. [PMID: 36979425 PMCID: PMC10046399 DOI: 10.3390/biom13030490] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 02/21/2023] [Accepted: 03/04/2023] [Indexed: 03/09/2023] Open
Abstract
Mounting evidence in the literature indicates an important role of endogenous and exogenous melatonin in driving physiological and molecular adaptations in livestock. Melatonin has been extensively studied in seasonally polyestrous animals whereby supplementation studies have been used to adjust circannual rhythms in herds of animals under abnormal photoperiodic conditions. Livestock undergo multiple metabolic and physiological adaptation processes throughout their production cycle which can result in decreased immune response leading to chronic illness, weight loss, or decreased production efficiency; however, melatonin’s antioxidant capacity and immunostimulatory properties could alleviate these effects. The cardiovascular system responds to melatonin and depending on receptor type and localization, melatonin can vasodilate or vasoconstrict several systemic arteries, thereby controlling whole animal nutrient partitioning via vascular resistance. Increased incidences of non-communicable diseases in populations exposed to circadian disruption have uncovered novel pathways of neurohormones, such as melatonin, influence health, and disease. Perturbations in immune function can negatively impact the growth and development of livestock which has been examined following melatonin supplementation. Specifically, melatonin can influence nutrient uptake, circulating nutrient profiles, and endocrine profiles controlling economically important livestock growth and development. This review focuses on the physiological, cellular, and molecular implications of melatonin on the health and disease of domesticated food animals.
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Yang J, Tang Q, Zeng Y. Melatonin: Potential avenue for treating iron overload disorders. Ageing Res Rev 2022; 81:101717. [PMID: 35961513 DOI: 10.1016/j.arr.2022.101717] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 07/10/2022] [Accepted: 08/08/2022] [Indexed: 02/08/2023]
Abstract
Iron overload as a highly risk factor, can be found in almost all human chronic and common diseases. Iron chelators are often used to treat iron overload; however, patient adherence to these chelators is poor due to obvious side effects and other disadvantages. Numerous studies have shown that melatonin has a high iron chelation ability and direct free radical scavenging activity, and can inhibit the lipid peroxidation process caused by iron overload. Therefore, melatonin may become potential complementary therapy for iron overload-related disorders due to its iron chelating and antioxidant activities. Here, the research progress of iron overload is reviewed and the therapeutic potential of melatonin in the treatment of iron overload is analyzed. In addition, studies related to the protective effects of melatonin on oxidative damage induced by iron overload are discussed. This review provides a foundation for preventing and treating iron homeostasis disorders with melatonin.
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Affiliation(s)
- Jiancheng Yang
- Department of Osteoporosis, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Qinghua Tang
- Department of Osteoporosis, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Yuhong Zeng
- Department of Osteoporosis, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China.
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Effects of Duodenal 5-Hydroxytryptophan Perfusion on Melatonin Synthesis in GI Tract of Sheep. Molecules 2021; 26:molecules26175275. [PMID: 34500708 PMCID: PMC8433724 DOI: 10.3390/molecules26175275] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 08/27/2021] [Accepted: 08/28/2021] [Indexed: 11/17/2022] Open
Abstract
The purpose of this study is to investigate the potential effects of 5-hydroxytryptophan (5-HTP) duodenal perfusion on melatonin (MT) synthesis in the gastrointestinal (GI) tract of sheep. 5-hydroxytryptophan is a precursor in the melatonin synthetic pathway. The results showed that this method significantly increased melatonin production in the mucosa of all segments in GI tract including duodenum, jejunum, ileum, cecum and colon. The highest melatonin level was identified in the colon and this indicates that the microbiota located in the colon may also participate in the melatonin production. In addition, portion of the melatonin generated by the GI tract can pass the liver metabolism and enters the circulation via portal vein. The current study provides further evidence to support that GI tract is the major site for melatonin synthesis and the GI melatonin also contributes to the circulatory melatonin level since plasma melatonin concentrations in 5-HTP treated groups were significantly higher than those in the control group. In conclusion, the results show that 10–50 mg of 5-HTP flowing into the duodenum within 6 h effectively improve the production of melatonin in the GI tract and melatonin concentration in sheep blood circulation during the day.
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Bonmati-Carrion MA, Tomas-Loba A. Melatonin and Cancer: A Polyhedral Network Where the Source Matters. Antioxidants (Basel) 2021; 10:antiox10020210. [PMID: 33535472 PMCID: PMC7912767 DOI: 10.3390/antiox10020210] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 01/24/2021] [Accepted: 01/25/2021] [Indexed: 12/11/2022] Open
Abstract
Melatonin is one of the most phylogenetically conserved signals in biology. Although its original function was probably related to its antioxidant capacity, this indoleamine has been “adopted” by multicellular organisms as the “darkness signal” when secreted in a circadian manner and is acutely suppressed by light at night by the pineal gland. However, melatonin is also produced by other tissues, which constitute its extrapineal sources. Apart from its undisputed chronobiotic function, melatonin exerts antioxidant, immunomodulatory, pro-apoptotic, antiproliferative, and anti-angiogenic effects, with all these properties making it a powerful antitumor agent. Indeed, this activity has been demonstrated to be mediated by interfering with various cancer hallmarks, and different epidemiological studies have also linked light at night (melatonin suppression) with a higher incidence of different types of cancer. In 2007, the World Health Organization classified night shift work as a probable carcinogen due to circadian disruption, where melatonin plays a central role. Our aim is to review, from a global perspective, the role of melatonin both from pineal and extrapineal origin, as well as their possible interplay, as an intrinsic factor in the incidence, development, and progression of cancer. Particular emphasis will be placed not only on those mechanisms related to melatonin’s antioxidant nature but also on the recently described novel roles of melatonin in microbiota and epigenetic regulation.
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Affiliation(s)
- Maria-Angeles Bonmati-Carrion
- Chronobiology Laboratory, Department of Physiology, IMIB-Arrixaca, University of Murcia, 30100 Murcia, Spain
- Ciber Fragilidad y Envejecimiento Saludable, 28090 Madrid, Spain
- Correspondence: (M.-A.B.-C.); (A.T.-L.)
| | - Antonia Tomas-Loba
- Circadian Rhythm and Cancer Laboratory, Department of Physiology, IMIB-Arrixaca, University of Murcia, 30120 Murcia, Spain
- Correspondence: (M.-A.B.-C.); (A.T.-L.)
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Prusik M, Lewczuk B. Diurnal Rhythm of Plasma Melatonin Concentration in the Domestic Turkey and Its Regulation by Light and Endogenous Oscillators. Animals (Basel) 2020; 10:ani10040678. [PMID: 32294963 PMCID: PMC7222729 DOI: 10.3390/ani10040678] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 04/10/2020] [Accepted: 04/10/2020] [Indexed: 12/16/2022] Open
Abstract
Simple Summary Environmental light regulates a wide range of phenomena in almost all organisms on Earth. Daily and seasonal changes in the photoperiod duration are the most important factors controlling the secretion of melatonin (MLT), a pineal hormone that affects many physiological processes in birds. The results of previous studies on the effect of MLT on the productivity and health of poultry have been promising. However, there are very few studies on the daily profiles of plasma MLT concentrations in domestic birds; therefore, we decided to examine plasma MLT levels in 10-week-old domestic turkeys exposed to different light conditions. The results demonstrated that plasma MLT concentration in turkeys kept under a 12 h light: 12 h dark cycle showed a prominent diurnal rhythm. Night-time light exposure caused a rapid decrease in plasma MLT concentrations. The housing of turkeys in continuous dim red light revealed endogenously generated diurnal rhythm of MLT secretion. The rhythm of the plasma MLT level in a reversed cycle of 12 h dark: 12 h light adapted quickly to the new lighting condition. Abstract The aim of this study was to characterize the diurnal rhythm of plasma melatonin (MLT) concentration and its regulation by light and endogenous oscillators in 10-week-old domestic turkeys. Three experiments were performed to examine (i) the course of daily changes in plasma MLT concentration in turkeys kept under a 12 h light: 12 h dark (12L:12D) cycle; (ii) the influence of night-time light exposure lasting 0.5, 1, 2, or 3 h on the plasma MLT level; and (iii) the occurrence of circadian fluctuations in plasma MLT levels in birds kept under continuous dim red light and the ability of turkeys to adapt their pineal secretory activity to a reversed light-dark cycle (12D:12L). The plasma MLT concentration was measured with a direct radioimmunoassay. The plasma MLT concentration in turkeys kept under a 12L:12D cycle changed significantly in a daily rhythm. It was low during the photophase and increased stepwise after the onset of darkness to achieve the maximal level in the middle of the scotophase. Next, it decreased during the second half of the night. The difference between the lowest level of MLT and the highest level was approximately 18-fold. The exposure of turkeys to light during the scotophase caused a rapid, large decrease in plasma MLT concentration. The plasma MLT concentration decreased approximately 3- and 10-fold after 0.5 and 1 h of light exposure, respectively, and reached the day-time level after 2 h of exposure. In turkeys kept under continuous darkness, the plasma MLT level was approximately 2.5-fold higher at 02:00 h than at 14:00 h. In birds kept under 12D:12L, the plasma MLT level was significantly higher at 14:00 h than at 02:00 h. The results showed that plasma MLT concentrations in 10-week-old turkeys have a prominent diurnal rhythm, which is endogenously generated and strongly influenced by environmental light.
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Khizhkin EA, Ilyukha VA, Vinogradova IA, Anisimov VN. Absence of Photoperiodism and Digestive Enzymes in Rats: The Role of Age and the Endogenous Melatonin Level. ADVANCES IN GERONTOLOGY 2020. [DOI: 10.1134/s2079057019040106] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Mannino G, Caradonna F, Cruciata I, Lauria A, Perrone A, Gentile C. Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin-1β. J Pineal Res 2019; 67:e12598. [PMID: 31349378 DOI: 10.1111/jpi.12598] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2019] [Revised: 06/24/2019] [Accepted: 07/16/2019] [Indexed: 12/21/2022]
Abstract
Melatonin is the main secretory product of the pineal gland, and it is involved in the regulation of periodic events. A melatonin production independent of the photoperiod is typical of the gut. However, the local physiological role of melatonin at the intestinal tract is poorly characterized. In this study, we evaluated the anti-inflammatory activities of melatonin in an in vitro model of inflamed intestinal epithelium. To this purpose, we assessed different parameters usually associated with intestinal inflammation using IL-1β-stimulated Caco-2 cells. Differentiated monolayers of Caco-2 cells were preincubated with melatonin (1 nmol/L-50 μmol/L) and then exposed to IL-1β. After each treatment, different inflammatory mediators, DNA-breakage, and global DNA methylation status were assayed. To evaluate the involvement of melatonin membrane receptors, we also exposed differentiated monolayers to melatonin in the presence of luzindole, a MT1 and MT2 antagonist. Our results showed that melatonin, at concentrations similar to those obtained in the lumen gut after ingestion of dietary supplements for the treatment of sleep disorders, was able to attenuate the inflammatory response induced by IL-1β. Anti-inflammatory effects were expressed as both a decrease of the levels of inflammatory mediators, including IL-6, IL-8, COX-2, and NO, and a reduced increase in paracellular permeability. Moreover, the protection was associated with a reduced NF-κB activation and a prevention of DNA demethylation. Conversely, luzindole did not reverse the melatonin inhibition of stimulated-IL-6 release. In conclusion, our findings suggest that melatonin, through a local action, can modulate inflammatory processes at the intestinal level, offering new opportunities for a multimodal management of IBD.
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Affiliation(s)
- Giuseppe Mannino
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, Italy
| | - Fabio Caradonna
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, Italy
| | - Ilenia Cruciata
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, Italy
| | - Antonino Lauria
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, Italy
| | - Anna Perrone
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, Italy
| | - Carla Gentile
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, Italy
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Majka J, Wierdak M, Brzozowska I, Magierowski M, Szlachcic A, Wojcik D, Kwiecien S, Magierowska K, Zagajewski J, Brzozowski T. Melatonin in Prevention of the Sequence from Reflux Esophagitis to Barrett's Esophagus and Esophageal Adenocarcinoma: Experimental and Clinical Perspectives. Int J Mol Sci 2018; 19:2033. [PMID: 30011784 PMCID: PMC6073539 DOI: 10.3390/ijms19072033] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Revised: 07/08/2018] [Accepted: 07/10/2018] [Indexed: 12/14/2022] Open
Abstract
Melatonin is a tryptophan-derived molecule with pleiotropic activities which is produced in all living organisms. This "sleep" hormone is a free radical scavenger, which activates several anti-oxidative enzymes and mechanisms. Melatonin, a highly lipophilic hormone, can reach body target cells rapidly, acting as the circadian signal to alter numerous physiological functions in the body. This indoleamine can protect the organs against a variety of damaging agents via multiple signaling. This review focused on the role played by melatonin in the mechanism of esophagoprotection, starting with its short-term protection against acute reflux esophagitis and then investigating the long-term prevention of chronic inflammation that leads to gastroesophageal reflux disease (GERD) and Barrett's esophagus. Since both of these condition are also identified as major risk factors for esophageal carcinoma, we provide some experimental and clinical evidence that supplementation therapy with melatonin could be useful in esophageal injury by protecting various animal models and patients with GERD from erosions, Barrett's esophagus and neoplasia. The physiological aspects of the synthesis and release of this indoleamine in the gut, including its release into portal circulation and liver uptake is examined. The beneficial influence of melatonin in preventing esophageal injury from acid-pepsin and acid-pepsin-bile exposure in animals as well as the usefulness of melatonin and its precursor, L-tryptophan in prophylactic and supplementary therapy against esophageal disorders in humans, are also discussed.
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Affiliation(s)
- Jolanta Majka
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland.
| | - Mateusz Wierdak
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland.
| | - Iwona Brzozowska
- Department of Anatomy, Faculty of Medicine, Jagiellonian University Medical College, 33-332 Cracow, Poland.
| | - Marcin Magierowski
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland.
| | - Aleksandra Szlachcic
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland.
| | - Dagmara Wojcik
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland.
| | - Slawomir Kwiecien
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland.
| | - Katarzyna Magierowska
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland.
| | - Jacek Zagajewski
- Department of Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, 31-034 Cracow, Poland.
| | - Tomasz Brzozowski
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland.
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Liu L, Zhang S, Bao J, He X, Tong D, Chen C, Ying Q, Zhang Q, Zhang C, Li J. Melatonin Improves Laying Performance by Enhancing Intestinal Amino Acids Transport in Hens. Front Endocrinol (Lausanne) 2018; 9:426. [PMID: 30105005 PMCID: PMC6077205 DOI: 10.3389/fendo.2018.00426] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Accepted: 07/09/2018] [Indexed: 01/11/2023] Open
Abstract
The high concentration of melatonin (MEL) in the intestinal mucosa suggests that it has a special physiological function in intestine. In hens, previous studies have shown that MEL treatment promoted egg-laying performance. Considering the importance of amino acids (AA) for egg formation, we hypothesized that MEL may enhance the intestinal absorption of AA from the feed, thus promoting egg laying performance. In this study, we supplemented the hens with MEL for two consecutive weeks. The results showed that, compared with control group, feeding with 0.625 mg MEL/kg diets gave rise to higher egg laying rate (by 4.3%, P = 0.016), increased eggshell thickness (by 16.9%, P < 0.01) and albumen height (by 4.5%, P = 0.042). Meanwhile, feeding with 0.625 and 2.5 mg MEL/kg diets could significantly increase serum levels of aspartic acid, threonine, serine, glutamic acid, glycine, alanine, isoleucine, leucine, tyrosine, phenylalanine, lysine, histidine, arginine, and proline. Furthermore, a 0.625 mg MEL/kg diets could significantly increase the expression of PepT1 (by 3949.9%), B0AT (by 6045.9%), b0, +AT (by 603.5%), and EAAT3 (by 412.7%) in the jejunum. Additionally, in the cultured intestinal crypt "organoids," treatment with 0.5 μM MEL could significantly enhance the expression of PepT1, b0, +AT and EAAT3 mRNAs by 35.4%, 110.0%, and 160.1%, respectively. Detection of MEL concentration in serum and intestinal fluid suggested that lower dosage of MEL feeding was mainly acted on intestine locally, and further increased intestinal antioxidases (GPx-3, SOD-1 or PRDX-3) mRNA expression. Taken together, we demonstrated that MEL feeding in laying hens could locally promote the expression and function of AA transporter in small intestine by up-regulating antioxidases expression, and finally elevate laying performance.
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Affiliation(s)
- Lijuan Liu
- Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Siyu Zhang
- Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Jiayang Bao
- Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Xiaowen He
- Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Danni Tong
- Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Cong Chen
- Yanping Bureau of Animal Husbandry, Veterinary & Aquatic Products, Nanping, China
| | | | - Qing Zhang
- Yanping Bureau of Animal Husbandry, Veterinary & Aquatic Products, Nanping, China
| | - Caiqiao Zhang
- Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, China
- *Correspondence: Jian Li
| | - Jian Li
- Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, China
- Caiqiao Zhang
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Boumans IJMM, de Boer IJM, Hofstede GJ, la Fleur SE, Bokkers EAM. The importance of hormonal circadian rhythms in daily feeding patterns: An illustration with simulated pigs. Horm Behav 2017; 93:82-93. [PMID: 28514644 DOI: 10.1016/j.yhbeh.2017.05.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2016] [Revised: 03/10/2017] [Accepted: 05/10/2017] [Indexed: 10/19/2022]
Abstract
The interaction between hormonal circadian rhythms and feeding behaviour is not well understood. This study aimed to deepen our understanding of mechanisms underlying circadian feeding behaviour in animals, using pigs, Sus scrofa, as a case study. Pigs show an alternans feeding pattern, that is, a small peak of feed intake at the beginning of the day and a larger peak at the end of the day. We simulated the feeding behaviour of pigs over a 24h period. The simulation model contained mechanisms that regulate feeding behaviour of animals, including: processing of feed in the gastrointestinal tract, fluctuation in energy balance, circadian rhythms of melatonin and cortisol and motivational decision-making. From the interactions between these various processes, feeding patterns (e.g. feed intake, meal frequency, feeding rate) emerge. These feeding patterns, as well as patterns for the underlying mechanisms (e.g. energy expenditure), fitted empirical data well, indicating that our model contains relevant mechanisms. The circadian rhythms of cortisol and melatonin explained the alternans pattern of feeding in pigs. Additionally, the timing and amplitude of cortisol peaks affected the diurnal and nocturnal peaks in feed intake. Furthermore, our results suggest that circadian rhythms of other hormones, such as leptin and ghrelin, are less important in circadian regulation of feeding behaviour than previously thought. These results are relevant to animal species with a metabolic and endocrine system similar to that of pigs, such as humans. Moreover, the modelling approach to understand feeding behaviour can be applied to other animal species.
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Affiliation(s)
- Iris J M M Boumans
- Animal Production Systems Group, Wageningen University, Wageningen, The Netherlands.
| | - Imke J M de Boer
- Animal Production Systems Group, Wageningen University, Wageningen, The Netherlands
| | - Gert Jan Hofstede
- Information Technology Group, Wageningen University, Wageningen, The Netherlands
| | - Susanne E la Fleur
- Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands
| | - Eddie A M Bokkers
- Animal Production Systems Group, Wageningen University, Wageningen, The Netherlands
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21
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Muñoz-Pérez JL, López-Patiño MA, Álvarez-Otero R, Gesto M, Soengas JL, Míguez JM. Characterization of melatonin synthesis in the gastrointestinal tract of rainbow trout (Oncorhynchus mykiss): distribution, relation with serotonin, daily rhythms and photoperiod regulation. J Comp Physiol B 2016; 186:471-84. [DOI: 10.1007/s00360-016-0966-4] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2015] [Revised: 01/22/2016] [Accepted: 01/25/2016] [Indexed: 10/22/2022]
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22
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Söderquist F, Hellström PM, Cunningham JL. Human gastroenteropancreatic expression of melatonin and its receptors MT1 and MT2. PLoS One 2015; 10:e0120195. [PMID: 25822611 PMCID: PMC4378860 DOI: 10.1371/journal.pone.0120195] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2015] [Accepted: 02/05/2015] [Indexed: 12/29/2022] Open
Abstract
Background and Aim The largest source of melatonin, according to animal studies, is the gastrointestinal (GI) tract but this is not yet thoroughly characterized in humans. This study aims to map the expression of melatonin and its two receptors in human GI tract and pancreas using microarray analysis and immunohistochemistry. Method Gene expression data from normal intestine and pancreas and inflamed colon tissue due to ulcerative colitis were analyzed for expression of enzymes relevant for serotonin and melatonin production and their receptors. Sections from paraffin-embedded normal tissue from 42 individuals, representing the different parts of the GI tract (n=39) and pancreas (n=3) were studied with immunohistochemistry using antibodies with specificity for melatonin, MT1 and MT2 receptors and serotonin. Results Enzymes needed for production of melatonin are expressed in both GI tract and pancreas tissue. Strong melatonin immunoreactivity (IR) was seen in enterochromaffin (EC) cells partially co-localized with serotonin IR. Melatonin IR was also seen in pancreas islets. MT1 and MT2 IR were both found in the intestinal epithelium, in the submucosal and myenteric plexus, and in vessels in the GI tract as well as in pancreatic islets. MT1 and MT2 IR was strongest in the epithelium of the large intestine. In the other cell types, both MT2 gene expression and IR were generally elevated compared to MT1. Strong MT2, IR was noted in EC cells but not MT1 IR. Changes in gene expression that may result in reduced levels of melatonin were seen in relation to inflammation. Conclusion Widespread gastroenteropancreatic expression of melatonin and its receptors in the GI tract and pancreas is in agreement with the multiple roles ascribed to melatonin, which include regulation of gastrointestinal motility, epithelial permeability as well as enteropancreatic cross-talk with plausible impact on metabolic control.
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MESH Headings
- Adult
- Case-Control Studies
- Colitis, Ulcerative/genetics
- Colitis, Ulcerative/metabolism
- Colitis, Ulcerative/pathology
- Enterochromaffin Cells/metabolism
- Gastrointestinal Tract/anatomy & histology
- Gastrointestinal Tract/metabolism
- Gene Expression
- Humans
- Immunohistochemistry
- Melatonin/metabolism
- Pancreas/anatomy & histology
- Pancreas/metabolism
- Receptor, Melatonin, MT1/genetics
- Receptor, Melatonin, MT1/metabolism
- Receptor, Melatonin, MT2/genetics
- Receptor, Melatonin, MT2/metabolism
- Serotonin/metabolism
- Tissue Distribution
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Affiliation(s)
- Fanny Söderquist
- Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden
| | - Per M. Hellström
- Department of Medical Sciences, Gastroenterology/Hepatology, Uppsala University, Uppsala, Sweden
| | - Janet L. Cunningham
- Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden
- * E-mail:
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Acuña-Castroviejo D, Escames G, Venegas C, Díaz-Casado ME, Lima-Cabello E, López LC, Rosales-Corral S, Tan DX, Reiter RJ. Extrapineal melatonin: sources, regulation, and potential functions. Cell Mol Life Sci 2014; 71:2997-3025. [PMID: 24554058 PMCID: PMC11113552 DOI: 10.1007/s00018-014-1579-2] [Citation(s) in RCA: 752] [Impact Index Per Article: 68.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2013] [Revised: 01/26/2014] [Accepted: 01/27/2014] [Indexed: 12/15/2022]
Abstract
Endogenous melatonin is synthesized from tryptophan via 5-hydroxytryptamine. It is considered an indoleamine from a biochemical point of view because the melatonin molecule contains a substituted indolic ring with an amino group. The circadian production of melatonin by the pineal gland explains its chronobiotic influence on organismal activity, including the endocrine and non-endocrine rhythms. Other functions of melatonin, including its antioxidant and anti-inflammatory properties, its genomic effects, and its capacity to modulate mitochondrial homeostasis, are linked to the redox status of cells and tissues. With the aid of specific melatonin antibodies, the presence of melatonin has been detected in multiple extrapineal tissues including the brain, retina, lens, cochlea, Harderian gland, airway epithelium, skin, gastrointestinal tract, liver, kidney, thyroid, pancreas, thymus, spleen, immune system cells, carotid body, reproductive tract, and endothelial cells. In most of these tissues, the melatonin-synthesizing enzymes have been identified. Melatonin is present in essentially all biological fluids including cerebrospinal fluid, saliva, bile, synovial fluid, amniotic fluid, and breast milk. In several of these fluids, melatonin concentrations exceed those in the blood. The importance of the continual availability of melatonin at the cellular level is important for its physiological regulation of cell homeostasis, and may be relevant to its therapeutic applications. Because of this, it is essential to compile information related to its peripheral production and regulation of this ubiquitously acting indoleamine. Thus, this review emphasizes the presence of melatonin in extrapineal organs, tissues, and fluids of mammals including humans.
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Affiliation(s)
- Darío Acuña-Castroviejo
- Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Avda. del Conocimiento s/n, Armilla, 18100, Granada, Spain,
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Chojnacki C, Wiśniewska-Jarosińska M, Kulig G, Majsterek I, Reiter RJ, Chojnacki J. Evaluation of enterochromaffin cells and melatonin secretion exponents in ulcerative colitis. World J Gastroenterol 2013; 19:3602-3607. [PMID: 23801861 PMCID: PMC3691046 DOI: 10.3748/wjg.v19.i23.3602] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2012] [Revised: 01/11/2013] [Accepted: 04/19/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To study an assessment of the number of enterochromaffin cells and expression of hydroxyindole-O-methyltransferase in colonic mucosa and urine excretion of 6-sulfatoxymelatonin in patients with ulcerative colitis.
METHODS: The study included 30 healthy subjects (group I-C), 30 patients with ulcerative proctitis [group II-ulcerative proctitis (UP)] and 30 patients with ulcerative colitis [group III-ulcerative colitis (UC)] in acute phases of these diseases. The number of enterochromaffin cells (EC) was estimated in rectal and colonic mucosa. Bioptates were assembled from many different parts of the large intestine. Immunorective cells collected from various parts of the colon were counted according to the Eurovision DAKO (Dako A/S, Copenhagen, Denmark) System in the range of 10 fields in each bioptate at × 200 magnification. The level of mRNA expression of hydroxyindole-O-methyltransferase (HIOMT) in colonic mucosa was estimated with RT-PCR. Urine 6-sulfatoxymelatonin (6-HMS) excretion was determined immunoenzymatically using an IBL (IBL International GmbH, Hamburg, Germany) kit (RE 54031).
RESULTS: The number of EC cells in healthy subjects (C) was 132.40 ± 31.26. In patients of group II (UP) and group III (UC) the number of these cells was higher - 225.40 ± 37.35 (P < 0.001) and - 225.24 ± 40.50 (P < 0.001) respectively. Similar differences were related to HIOMT expression, which was 1.04 ± 0.36 in group C, 1.56 ± 0.56 (P < 0.01) in group UP and 2.00 ± 0.35 (P < 0.001) in group UC. Twenty-four hour 6-HMS urinary excretion was as follows: C - 16.32 ± 4.95 μg/24 h, UP - 26.30 ± 7.29 μg/24 h (P < 0.01), UC - 42.30 ± 12.56 μg/24h (P < 0.001). A correlation between number of EC cells and 6-HMS excretion was noted in all groups: r = 0.766 in patients with UP, r = 0.703 with UC and r = 0.8551 in the control group; the correlation between the results is statistically significant.
CONCLUSION: In the acute phases of both UP and UC, proliferation of EC cells and high expression of HIOMT and urine excretion of 6-HMS is noted. These changes may represent a beneficial response in the anti-inflammatory and defense mechanism.
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Preclinical efficacy of melatonin to reduce methotrexate-induced oxidative stress and small intestinal damage in rats. Dig Dis Sci 2013; 58:959-69. [PMID: 23053903 DOI: 10.1007/s10620-012-2437-4] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2012] [Accepted: 09/26/2012] [Indexed: 12/12/2022]
Abstract
BACKGROUND Methotrexate is widely used as a chemotherapeutic agent for leukemia and other malignancies. The efficacy of this drug is often limited by mucositis and intestinal injury, which are the major causes of morbidity in children and adults. AIM The present study investigates whether melatonin, a powerful antioxidant, could have a protective effect. METHOD Rats were pretreated with melatonin (20 and 40 mg/kg body weight) daily 1 h before methotrexate (7 mg/kg body weight) administration for three consecutive days. After the final dose of methotrexate, the rats were sacrificed and the small intestine was used for light microscopy and biochemical assays. Intestinal homogenates were used for assay of oxidative stress parameters malondialdehyde and protein carbonyl content, and myeloperoxidase activity, a marker of neutrophil infiltration as well as for the activities of the antioxidant enzymes. RESULT Pretreatment with melatonin had a dose-dependent protective effect on methotrexate (MTX)-induced alterations in small intestinal morphology. Morphology was saved to some extent with 20 mg melatonin pretreatment and near normal morphology was achieved with 40 mg melatonin pretreatment. Biochemically, pretreatment with melatonin significantly attenuated MTX-induced oxidative stress (P < 0.01 for MDA, P < 0.001 for protein carbonyl content) and restored the activities of the antioxidant enzymes (glutathione reductase P < 0.05, superoxide dismutase P < 0.01). CONCLUSION The results of the present study demonstrate that supplementation by exogenous melatonin significantly reduces MTX-induced small intestinal damage, indicating that it may be beneficial in ameliorating MTX-induced enteritis in humans.
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Cekmez F, Cetinkaya M, Tayman C, Canpolat FE, Kafa IM, Uysal S, Tunc T, Sarıcı SÜ. Evaluation of melatonin and prostaglandin E1 combination on necrotizing enterocolitis model in neonatal rats. ACTA ACUST UNITED AC 2013; 184:121-5. [PMID: 23524022 DOI: 10.1016/j.regpep.2013.03.016] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2012] [Revised: 02/11/2013] [Accepted: 03/03/2013] [Indexed: 11/18/2022]
Abstract
BACKGROUND Necrotizing enterocolitis (NEC) is one of the most common gastrointestinal emergencies in newborn infants but up to now there is no completely effective treatment for it. OBJECTIVE In order to show that a combination of melatonin and prostaglandins may be useful to save lives, we use newborn rat as a model of necrotizing enterocolitis to test the hypothesis of using the combination therapy might have more potential effect on mucosal cytoprotection and healing. PATIENTS AND METHODS A total of 60 newborn pups from 5 time-mated Sprague-Dawley pregnant rats were divided equally into 5 groups as follows: NEC (subjected to NEC), NEC+Melatonin, NEC+Prostaglandin, NEC+Prostaglandin+Melatonin and control. These animals were fed with hyperosmolar formula 3 times daily and subjected to 100% CO2 inhalation for 10 min, +4°C cold exposure for 5 min, and 97% O2 for 5 min twice daily to induce NEC. This procedure was applied to the pups for 3 days. RESULTS The macroscopic scoring, intestinal injury scoring and apoptosis index scoring were all found to be significantly lower in NEC+Prostaglandin+Melatonin group compared with NEC group. Anti-oxidant enzyme activities were significantly higher, whereas lipid peroxidation was significantly lower in NEC+Prostaglandin+Melatonin group compared with NEC group. CONCLUSION This combination therapy showed cytoprotective and healing effects on mucosa in the intestinal tissue of rat pups in necrotizing enterocolitis model. Therefore, this therapy might also show benefit in preterm infants with NEC. After confirmation of this data by other clinical and experimental studies, it may be a novel therapeutic option for the prevention of NEC in preterm infants.
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A preclinical study on the protective effect of melatonin against methotrexate-induced small intestinal damage: effect mediated by attenuation of nitrosative stress, protein tyrosine nitration, and PARP activation. Cancer Chemother Pharmacol 2013; 71:1209-18. [PMID: 23420439 DOI: 10.1007/s00280-013-2115-z] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2012] [Accepted: 02/05/2013] [Indexed: 10/27/2022]
Abstract
PURPOSE One of the major toxic side effects of methotrexate (MTX) is enterocolitis. To date, there is no efficient standard treatment for this side effect. Nitrosative stress is reported to play a critical role in MTX-induced mucositis. The purpose of this study is to investigate whether pretreatment with melatonin, an inhibitor of nitro-oxidative stress, prevents MTX-induced mucositis in rats. METHODS Rats were pretreated with melatonin (20 and 40 mg/kg body weight) i.p. daily 1 h before MTX (7 mg/kg body weight) administration for three consecutive days. After the final dose of MTX, the rats were killed and the small intestines were used for analysis. RESULTS The small intestines of MTX-treated rats showed moderate to severe injury. The villi were distorted, blunted, and atrophied and focally absent in various segments of the small intestines. Crypt abscesses were also found, suggesting an inflammatory response. Pretreatment with melatonin had a dose-dependent protective effect on MTX-induced mucositis. Morphology was saved to a moderate extent with 20 mg melatonin pretreatment, and near-normal morphology was achieved with 40 mg melatonin pretreatment. Damage to the villi and crypt abscess was reduced. The villi/crypt ratio was almost restored. Melatonin pretreatment protected the small intestines from MTX-induced damage by attenuating nitrosative stress, protein tyrosine nitration and PARP expression. CONCLUSION Because of its versatility in protecting against nitro-oxidative stress and reducing inflammation, we suggest that melatonin could be beneficial in ameliorating MTX-induced enteritis in humans.
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Chojnacki C, Wachowska-Kelly P, Błasiak J, Reiter RJ, Chojnacki J. Melatonin secretion and metabolism in patients with hepatic encephalopathy. J Gastroenterol Hepatol 2013. [PMID: 23190028 DOI: 10.1111/jgh.12055] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM The rhythm of melatonin secretion and its blood level changes in cirrhotic patients, but the causes of these alterations have not been sufficiently appreciated. The aim of study was to estimate the dependence between melatonin secretion and metabolism and the severity of hepatic encephalopathy. METHODS The study included 75 alcoholic cirrhotic patients (A, B, C) with hepatic insufficiency and 25 healthy subjects (group K). Three groups of patients were identified, 25 patients each, with grade 1, 2, and 3 hepatic encephalopathy according to West-Haven Scale. Immunoenzymatic method was used to measure serum melatonin (at 02:00 h and 09:00 h) level and 6-sulfatoxymelatonin (6-HMS) excretion in the urine (during night and day). RESULTS Nocturnal serum melatonin levels (pg/mL) in groups were: K-57.1 ± 11.4, A-38.5 ± 11.2, B-53.4 ± 17.9, C-79.5 ± 27.9 (P < 0.01); whereas diurnal levels were: K-10.9 ± 3.5, A-33.5 ± 12.0, B-53.8 ± 23.1, C-98.5 ± 34.6 (P < 0.01). Similar differences were found in the evaluation of 6-HMS excretion (μg/9 h) in urine at night: group K-23.4 ± 14.4, A-16.6 ± 5.4, B-14.3 ± 6.2 (P < 0.01), C-3.3 ± 1.5 (P < 0.001). Diurnal 6-HMS excretion (μg/15 h) was lower only in group C and it was respectively: K-6.9 ± 3.4, A-7.1 ± 1.7, B-7.6 ± 1.7, C-4.3 ± 2.2 (P < 0.001). Serum ammonia concentrations (μg/dL) were: group K-30.4 ± 8.9, A-51.8 ± 25.4 (P < 0.05), B-73.0 ± 29.8 (P < 0.001), C-107.5 ± 34.8 (P < 0.001). No correlation between melatonin and ammonia levels in all groups was found. CONCLUSIONS The elevated melatonin blood levels both at night and day may account for some of the clinical manifestations of hepatic encephalopathy (daytime sleepiness, fatigue).
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Affiliation(s)
- Cezary Chojnacki
- Department of Gastroenterology, Medical University of Lodz, Lodz, Poland
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Melatonin levels in serum and ascitic fluid of patients with hepatic encephalopathy. Gastroenterol Res Pract 2012; 2012:510764. [PMID: 23346104 PMCID: PMC3546494 DOI: 10.1155/2012/510764] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2012] [Accepted: 12/04/2012] [Indexed: 01/24/2023] Open
Abstract
Cirrhotic patients exhibit disturbed melatonin homeostasis, which may lead to sleep disturbances, but an influence on the hepatic encephalopathy has not been elucidated. Aim. In the present study, the association of melatonin levels in serum and ascitic fluid and ammonia concentration related to the intensity of hepatic encephalopathy (HE) was investigated.
Material and Methods. The study included 90 alcoholic patients with hepatic encephalopathy and 30 healthy volunteers (C). Patients were divided in three groups according to 0–4 West-Haven Score: HE1 (n = 28), HE2 (n = 30), and HE3 (n = 32). Melatonin was measured by radioimmune assay. Results. In fasting patients with hepatic encephalopathy we noted higher melatonin serum levels [pg/mL] than in healthy subjects groups: C—11.3 ± 3.9, HE1 – 34.3 ± 12.2 (P < 0.01), HE2—54.8 ± 23.9, and HE3—119.8 ± 96.4 (P < 0.001). No correlation between melatonin and ammonia levels was found. Melatonin was detected in ascetic fluid in 24 patients of group HE2 and 27 patients of group HE2 of hepatic encephalopathy. Conclusions. Our results suggest that high blood levels of melatonin in cirrhotic liver patients may account for some of the clinical manifestations of hepatic encephalopathy, for example, daytime sleepiness, fatigue.
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Abstract
This review summarizes the metabolism, secretion, regulation and sites of action of melatonin. An updated description of the melatonin receptors, including their signal transduction mechanisms, distribution and characterization of receptor genes, is given. Special emphasis is focused on the clinical aspects and potential uses of melatonin in the sleep-wake rhythms, in the immune function, in cancer therapy, in neuroprotection against oxidative damage and antioxidant activities in different tissues. Finally, combined effects of melatonin with other drugs are discussed.
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Celinski K, Konturek SJ, Konturek PC, Brzozowski T, Cichoz-Lach H, Slomka M, Malgorzata P, Bielanski W, Reiter RJ. Melatonin or L-tryptophan accelerates healing of gastroduodenal ulcers in patients treated with omeprazole. J Pineal Res 2011; 50:389-394. [PMID: 21362032 DOI: 10.1111/j.1600-079x.2011.00855.x] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Melatonin and L-tryptophan (Trp) are highly gastroprotective in humans, but no study has assessed their impact on healing of chronic gastroduodenal ulcers in humans. Three groups (A, B and C) of 14 idiopathic patients in each treatment group with gastroduodenal chronic ulcers were treated with omeprazole (20 mg twice daily) combined either with placebo (group A), melatonin (group B) or with Trp (group C). The rate of ulcer healing was determined by gastroduodenoscopy at day 0, 7, 14 and 21 after initiation of therapy. Plasma melatonin, gastrin, ghrelin and leptin were measured by RIA. On day 7, omeprazole by itself (group A) had not healed any ulcers, but four ulcers were healed with omeprazole plus melatonin and two with omeprazole plus tryptophan. At day 21, all ulcers were healed in patients treated with melatonin or Trp, but only 10-12 ulcers were healed in placebo-treated patients. After treatment with omeprazole plus melatonin (group B) or Trp (group C), plasma melatonin levels rose several-fold above initial values. Plasma gastrin level also rose significantly during treatment with omeprazole plus melatonin or Trp, but it was also significantly increased in patients treated with omeprazole plus placebo. Plasma ghrelin levels did not change significantly after treatment with melatonin or Trp, while plasma leptin increased significantly in patients treated with melatonin or Trp but not with placebo. We conclude that melatonin or Trp, when added to omeprazole treatment, accelerates ulcer healing and this likely depends mainly upon the significant increments in plasma melatonin.
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Stürtz M, Cerezo AB, Cantos-Villar E, Garcia-Parrilla MC. Determination of the melatonin content of different varieties of tomatoes (Lycopersicon esculentum) and strawberries (Fragariaananassa). Food Chem 2011; 127:1329-34. [PMID: 25214134 DOI: 10.1016/j.foodchem.2011.01.093] [Citation(s) in RCA: 98] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2010] [Revised: 01/11/2011] [Accepted: 01/22/2011] [Indexed: 11/29/2022]
Abstract
Melatonin has recently been detected in various plants and foods. However, data regarding the food composition of melatonin are too scarce to evaluate dietary intake. This paper aims to identify melatonin unequivocally using LC-MS in a wide set of varieties of tomatoes (Lycopersicon esculentum) and strawberry (Fragariaananassa). Furthermore, a validated LC fluorescence was developed. This is the first time melatonin has been identified in Bond, Borsalina, Catalina, Gordal, Lucinda, Marbone, Myriade, Pitenza, Santonio, Perlino, Platero, and RAF varieties of tomatoes, as well as in strawberry (Fragaria ananassa): Camarosa, Candonga, Festival, and Primoris. Melatonin concentration was shown to vary greatly depending on the tomato varieties and harvests (2009, 2010), ranging from 4.11ng/g to 114.52ng/g fresh weight. However, the four varieties of strawberries collected during the two harvests showed greater similarity in melatonin (1.38-11.26ng/g fresh weight).
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Affiliation(s)
- Melanie Stürtz
- Área de Nutrición y Bromatología, Facultad de Farmacia, Universidad de Sevilla, c/P. García González 2, Sevilla E 41012, Spain
| | - Ana B Cerezo
- Área de Nutrición y Bromatología, Facultad de Farmacia, Universidad de Sevilla, c/P. García González 2, Sevilla E 41012, Spain
| | - E Cantos-Villar
- Instituto de Investigación y Formación Agraria y Pesquera (IFAPA), Rancho de La Merced, Ctra. Trebujena, Km 3.2, P.O. Box 40, 589, 11471 Jerez de la Frontera (Cádiz), Spain
| | - M C Garcia-Parrilla
- Área de Nutrición y Bromatología, Facultad de Farmacia, Universidad de Sevilla, c/P. García González 2, Sevilla E 41012, Spain.
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Fusani L, Cardinale M, Schwabl I, Goymann W. Food availability but not melatonin affects nocturnal restlessness in a wild migrating passerine. Horm Behav 2011; 59:187-92. [PMID: 21110977 DOI: 10.1016/j.yhbeh.2010.11.013] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2010] [Revised: 11/12/2010] [Accepted: 11/12/2010] [Indexed: 11/27/2022]
Abstract
A large number of passerine species migrate at night, although most of them are diurnal outside the migratory seasons. This diurnal-to-nocturnal transition is a major life-history event, yet little is known about its physiological control. Previous work showed that during the migratory periods captive birds showing nocturnal migratory restlessness (Zugunruhe) have reduced concentrations of circulating melatonin at night compared to non-migratory periods. This suggested that the hormone melatonin, a main component of the avian circadian system, is involved in the expression of Zugunruhe. Other studies demonstrated that the relationship between low melatonin levels and Zugunruhe is not a seasonal correlation. When Zugunruhe was interrupted by exposing birds to a fasting-and-refeeding protocol, melatonin levels increased. Here we studied whether melatonin and food availability influence the intensity of Zugunruhe in wild migrating garden warblers (Sylvia borin) at a stopover site. Birds were held in recording cages overnight, with or without food available, and either bled to determine melatonin concentrations or treated transdermally with melatonin. We found that melatonin levels at night were correlated with the intensity of diurnal locomotor activity and with condition, but were not correlated with Zugunruhe. Similarly, the melatonin treatment did not have effects on Zugunruhe, whereas food availability increased it. Our study shows that the nocturnal melatonin levels in migrating warblers depend on food availability and are correlated with condition. In addition, it suggests that melatonin does not control Zugunruhe and might rather be involved in energy conservation and/or clock synchronization during migration.
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Affiliation(s)
- Leonida Fusani
- Department of Biology and Evolution, University of Ferrara, Via Luigi Borsari 46, 44100 Ferrara, Italy.
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Andersson EA, Holst B, Sparsø T, Grarup N, Banasik K, Holmkvist J, Jørgensen T, Borch-Johnsen K, Egerod KL, Lauritzen T, Sørensen TIA, Bonnefond A, Meyre D, Froguel P, Schwartz TW, Pedersen O, Hansen T. MTNR1B G24E variant associates With BMI and fasting plasma glucose in the general population in studies of 22,142 Europeans. Diabetes 2010; 59:1539-48. [PMID: 20200315 PMCID: PMC2874716 DOI: 10.2337/db09-1757] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2009] [Accepted: 02/20/2010] [Indexed: 12/15/2022]
Abstract
OBJECTIVE Common variants in the melatonin receptor type 1B (MTNR1B) locus have been shown to increase fasting plasma glucose (FPG) and the risk of type 2 diabetes. The aims of this study were to evaluate whether nonsynonymous variants in MTNR1B associate with monogenic forms of hyperglycemia, type 2 diabetes, or related metabolic traits. RESEARCH DESIGN AND METHODS MTNR1B was sequenced in 47 probands with clinical maturity-onset diabetes of the young (MODY), in 51 probands with early-onset familial type 2 diabetes, and in 94 control individuals. Six nonsynonymous variants (G24E, L60R, V124I, R138C, R231H, and K243R) were genotyped in up to 22,142 Europeans. Constitutive and melatonin-induced signaling was characterized for the wild-type melatonin receptor type 1B (MT2) and the 24E, 60R, and 124I MT2 mutants in transfected COS-7 cells. RESULTS No mutations in MTNR1B were MODY specific, and none of the investigated MTNR1B variants associated with type 2 diabetes. The common 24E variant associated with increased prevalence of obesity (odds ratio 1.20 [1.08-1.34]; P = 8.3 x 10(-4)) and increased BMI (beta = 0.5 kg/m(2); P = 1.2 x 10(-5)) and waist circumference (beta = 1.2 cm; P = 9 x 10(-6)) in combined Danish and French study samples. 24E also associated with decreased FPG (beta = -0.08 mmol/l; P = 9.2 x 10(-4)) in the Danish Inter99 population. Slightly decreased constitutive activity was observed for the MT2 24E mutant, while the 124I and 60R mutants displayed considerably decreased or completely disrupted signaling, respectively. CONCLUSIONS Nonsynonymous mutations in MTNR1B are not a common cause of MODY or type 2 diabetes among Danes. MTNR1B 24E associates with increased body mass and decreased FPG. Decreased MT2 signaling does apparently not directly associate with FPG or type 2 diabetes.
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Al-Ghoul WM, Abu-Shaqra S, Park BG, Fazal N. Melatonin plays a protective role in postburn rodent gut pathophysiology. Int J Biol Sci 2010; 6:282-93. [PMID: 20567497 PMCID: PMC2878173 DOI: 10.7150/ijbs.6.282] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2009] [Accepted: 05/11/2010] [Indexed: 11/16/2022] Open
Abstract
Melatonin is a possible protective agent in postburn gut pathophysiological dynamics. We investigated the role of endogenously-produced versus exogenously-administered melatonin in a major thermal injury rat model with well-characterized gut inflammatory complications. Our rationale is that understanding in vivo melatonin mechanisms in control and inflamed tissues will improve our understanding of its potential as a safe anti-inflammatory/antioxidant therapeutic alternative. Towards this end, we tested the hypothesis that the gut is both a source and a target for melatonin and that mesenteric melatonin plays an anti-inflammatory role following major thermal injury in rats with 3rd degree hot water scald over 30% TBSA. Our methods for assessing the gut as a source of melatonin included plasma melatonin ELISA measurements in systemic and mesenteric circulation as well as rtPCR measurement of jejunum and terminal ileum expression of the melatonin synthesizing enzymes arylalkylamine N-acetyltransferase (AA-NAT) and 5-hydroxyindole-O-methyltransferase (HIOMT) in sham versus day-3 postburn rats. Our melatonin ELISA results revealed that mesenteric circulation has much higher melatonin than systemic circulation and that both mesenteric and systemic melatonin levels are increased three days following major thermal injury. Our rtPCR results complemented the ELISA data in showing that the melatonin synthesizing enzymes AA-NAT and HIOMT are expressed in the ileum and jejunum and that this expression is increased three days following major thermal injury. Interestingly, the rtPCR data also revealed negative feedback by melatonin as exogenous melatonin supplementation at a dose of 7.43 mg (32 μmole/kg), but not 1.86 mg/kg (8 μmole/kg) drastically suppressed AA-NAT mRNA expression. Our methods also included an assessment of the gut as a target for melatonin utilizing computerized immunohistochemical measurements to quantify the effects of exogenous melatonin supplementation on postburn gut mucosa barrier inflammatory profiles. Here, our results revealed that daily postburn intraperitoneal melatonin administration at a dose of 1.86 mg/kg (8 μmole/kg) significantly suppressed both neutrophil infiltration and tyrosine nitrosylation as revealed by Gr-1 and nitrotyrosine immunohistochemistry, respectively. In conclusion, our results provide support for high mesenteric melatonin levels and dynamic de novo gut melatonin production, both of which increase endogenously in response to major thermal injury, but appear to fall short of abrogating the excessive postburn hyper-inflammation. Moreover, supplementation by exogenous melatonin significantly suppresses gut inflammation, thus confirming that melatonin is protective against postburn inflammation.
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Affiliation(s)
- Walid M Al-Ghoul
- Department of Biological Sciences, Chicago State University, Chicago, IL 60628, USA.
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Matheus N, Mendoza C, Iceta R, Mesonero JE, Alcalde AI. Melatonin inhibits serotonin transporter activity in intestinal epithelial cells. J Pineal Res 2010; 48:332-9. [PMID: 20210852 DOI: 10.1111/j.1600-079x.2010.00757.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Gastrointestinal serotonin (5-HT) and melatonin are two closely related neuromodulators which are synthesised in the enterochromaffin cells of the intestinal epithelium and which have been shown to be involved in the physiopathology of the gastrointestinal tract. The effects of 5-HT depend on 5-HT availability which is, in part, modulated by the serotonin transporter (SERT). This transporter provides an efficient 5-HT uptake after release and is expressed in the membrane of the enterocytes. Although the origin and effects of 5-HT and melatonin are similar, the interrelationship between them in the gastrointestinal tract is unknown. The main aim of this study was to determine whether melatonin affects SERT activity and expression, and, if so, to elucidate the mechanisms involved. Caco-2 cell line was used to carry out the study as these cells have been shown to endogenously express SERT. The results showed that melatonin inhibits SERT activity by affecting both V(max) and kt kinetic constants although SERT synthesis or intracellular trafficking did not appear to be affected. The melatonin effect seemed to be independent of melatonin receptors MT(1) and MT(2) and protein kinase C and cAMP intracellular pathways. Our results suggest that the inhibition of SERT might be due to a catalytic effect of melatonin on the allosteric citalopram-sensitive site in SERT. This study shows, for the first time, that melatonin modulates SERT activity, thus demonstrating the feedback system between melatonin and the serotoninergic system in the gastrointestinal tract.
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Affiliation(s)
- Nyurky Matheus
- Departamento de Farmacología y Fisiología, Universidad de Zaragoza, Spain
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Fagundes DS, Gonzalo S, Arruebo MP, Plaza MA, Murillo MD. Melatonin and Trolox ameliorate duodenal LPS-induced disturbances and oxidative stress. Dig Liver Dis 2010; 42:40-4. [PMID: 19501031 DOI: 10.1016/j.dld.2009.04.014] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2008] [Revised: 03/19/2009] [Accepted: 04/14/2009] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Lipopolysaccharide evokes gastrointestinal motility disturbances and oxidative stress. The aims of the present study were to investigate the effect of melatonin and Trolox in the actions of lipopolysaccharide on duodenal contractility and on lipid peroxidation in rabbit duodenum. METHODS The in vitro duodenal contractility studies were carried out in organ bath and the levels of malondialdehyde were assayed by spectrophotometry. Duodenal segments were incubated with lipopolysaccharide (0.3 microg mL(-1)). RESULTS Lipopolysaccharide decreased acetylcholine-induced contractions and increased malondialdehyde and 4-hydroxyalkenals concentrations in homogenates of duodenum. Melatonin reduced the amplitude of spontaneous contractions in duodenal muscle. Acetylcholine-induced contractions were not altered by melatonin in longitudinal and circular muscles. Trolox decreased the amplitude of spontaneous contractions of duodenal muscle. Trolox (1.2 or 4 mM) did not alter acetylcholine-induced contractions in duodenal muscle, but the concentration of 12 mM diminished the frequency of contractions and acetylcholine-induced contractions. Melatonin (0.3 mM) or Trolox (4 mM) diminished malondialdehyde and 4-hydroxyalkenals levels induced by lipopolysaccharide in the duodenum. CONCLUSIONS Melatonin and Trolox reduce oxidative stress induced by lipopolysaccharide and ameliorate the effect of lipopolysaccharide on duodenal contractility.
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Affiliation(s)
- D S Fagundes
- Pharmacology and Physiology Department (Physiology), Veterinary Faculty, Zaragoza University, Miguel Servet 177, 50013 Zaragoza, Spain
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Muñoz JL, Ceinos RM, Soengas JL, Míguez JM. A simple and sensitive method for determination of melatonin in plasma, bile and intestinal tissues by high performance liquid chromatography with fluorescence detection. J Chromatogr B Analyt Technol Biomed Life Sci 2009; 877:2173-7. [DOI: 10.1016/j.jchromb.2009.06.001] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2009] [Revised: 05/21/2009] [Accepted: 06/01/2009] [Indexed: 10/20/2022]
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Celinski K, Konturek PC, Slomka M, Cichoz-Lach H, Gonciarz M, Bielanski W, Reiter RJ, Konturek SJ. Altered basal and postprandial plasma melatonin, gastrin, ghrelin, leptin and insulin in patients with liver cirrhosis and portal hypertension without and with oral administration of melatonin or tryptophan. J Pineal Res 2009; 46:408-414. [PMID: 19552764 DOI: 10.1111/j.1600-079x.2009.00677.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
This investigation was designed to assess the effects of oral administration of melatonin (10 mg) and tryptophan (Trp) (500 mg) on fasting and postprandial plasma levels of melatonin, gastrin, ghrelin, leptin and insulin in 10 healthy controls and in age-matched patients with liver cirrhosis (LC) and portal hypertension. Fasting plasma melatonin levels in LC patients were about five times higher (102 +/- 15 pg/mL) than in healthy controls (22 +/- 3 pg/mL). These levels significantly increased postprandially in LC patients, but significantly less so in controls. Treatment with melatonin or L-Trp resulted in a further significant rise in plasma melatonin, both under fasting and postprandial conditions, particularly in LC patients. Moreover, plasma gastrin, ghrelin, leptin and insulin levels under fasting and postprandial conditions were significantly higher in LC subjects than in healthy controls and they further rose significantly after oral application of melatonin or Trp. This study shows that: (a) patients with LC and portal hypertension exhibit significantly higher fasting and postprandial plasma melatonin levels than healthy subjects; (b) plasma ghrelin, both in LC and healthy controls reach the highest values under fasting conditions, but decline postprandially, especially after oral application of melatonin or Trp; and (c) plasma melatonin, gastrin, ghrelin and insulin levels are altered significantly in LC patients with portal hypertension compared with that in healthy controls possibly due to their portal systemic shunting and decreased liver degradation.
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Affiliation(s)
- K Celinski
- Department of Gastroeneterology, Medical University of Lublin, Lublin, Poland
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Konturek PC, Konturek SJ, Burnat G, Brzozowski T, Brzozowska I, Reiter RJ. Dynamic physiological and molecular changes in gastric ulcer healing achieved by melatonin and its precursor L-tryptophan in rats. J Pineal Res 2008; 45:180-90. [PMID: 18298459 DOI: 10.1111/j.1600-079x.2008.00574.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Following induction of gastric ulcer in rats by serosal application of acetic acid, local mucosal necrosis ensues accompanied by a reduction in mucosal microcirculation and by almost immediate expression of inducible nitric oxide (NO) synthase (iNOS) and proinflammatory cytokines. Daily application of melatonin (20 mg/kg) or l-tryptophan (100 mg/kg) accelerates ulcer healing by affecting the cyclooxygenase-2 (COX-2)-prostaglandin (PG) system with excessive production of protective PG, especially in later period of ulcer healing. Furthermore, expression of hypoxia inducible factor, vascular-endothelial growth factor, an activation of cNOS-NO system and the stimulation of sensory nerves with the expression and release of calcitonin gene related peptide (CGRP) appear to aid the restoration of mucosal repair and microcirculation in the ulcer bed. The enhanced expression of the melatonin MT(2) receptors (MT(2)-R) combined with overexpression of key enzymes involved in biosynthesis of melatonin such as N-acetyltransferase and hydroxyindole-O-methyltransferase contribute to the acceleration of ulcer healing by this indole. Melatonin-induced acceleration of ulcer healing is also mediated by release of gastrin and ghrelin, the most potent stimulants of gastric mucosal cell proliferation and mucosal repair. These sequential steps in ulcer healing accelerated by melatonin can be interfered with by the blockade of MT(2)R, COX-2/PG and cNOS/NO systems, and by reduction in the inflammatory iNOS/NO system. Thus, melatonin and its precursor l-tryptophan, trigger the cascade of molecular events leading to the functional improvement in ulcer healing.
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Affiliation(s)
- Peter C Konturek
- Department of Internal Medicine, Erlangen-Nuremberg University, Erlangen, Germany.
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Nisbet DJ, Edrington TS, McReynolds JL, Callaway TR, Byrd JA. Influence of exogenous melatonin administration on Salmonella enteritidis colonization in molted layers. Poult Sci 2008; 87:1083-8. [PMID: 18492995 DOI: 10.3382/ps.2008-00016] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Two studies were conducted to evaluate the effects of melatonin on Salmonella Enteritidis infection in experimentally challenged laying hens subjected to a forced molt. Leghorn hens (>50 wk of age) were randomly assigned to rooms, acclimated to a 16L:8D regimen, and provided ad libitum access to a nonmedicated mash layer diet and water. Birds in one room were molted (8L:16D; complete feed withdrawal), whereas birds in the second room served as nonmolted controls (CONT). Within each room, birds were randomly assigned to melatonin treatment (MEL; 12 birds/treatment), dosed orally commencing the same day as feed withdrawal for 10 d: (experiment I: 0 or 5 mg of melatonin; experiment II: 0, 10, or 20 mg of melatonin). Three days following feed withdrawal, all birds were experimentally infected with Salmonella Enteritidis, and after 10 d of feed withdrawal, all birds were killed and necropsied. In experiment I, concentrations of Salmonella Enteritidis in the cecal contents and the number of Salmonella Enteritidis-positive tissues from the crop, ceca, liver, spleen, and ovary were higher (P < 0.0001) in the MOLT compared with the CONT treatments. No differences (P > 0.10) were observed in any of the parameters examined due to MEL treatment. For experiment II, cecal concentrations of Salmonella Enteritidis were generally higher in the MOLT compared with the CONT treatment and within molted birds, cecal concentrations were higher in the MEL treatment (P < 0.05). Melatonin treatment in molted birds increased (P < 0.05) the percentage of positive crops in the MOLT+20 MEL treatment (P < 0.05). Salmonella-positive cecal tissue was increased (P < 0.001) in MOLT compared with CONT birds and was also higher in MOLT+10 MEL and MOLT+20 MEL birds compared with the MOLT-only treatment. Results from the current research suggest that dosage with high levels of melatonin may exacerbate Salmonella Enteritidis infection in layers subjected to forced molt.
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Affiliation(s)
- D J Nisbet
- Food and Feed Safety Research Unit, Southern Plains Agricultural Research Center, USDA-ARS, College Station, TX 77845, USA.
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Ceinos RM, Polakof S, Illamola AR, Soengas JL, Míguez JM. Food deprivation and refeeding effects on pineal indoles metabolism and melatonin synthesis in the rainbow trout Oncorhynchus mykiss. Gen Comp Endocrinol 2008; 156:410-7. [PMID: 18275959 DOI: 10.1016/j.ygcen.2008.01.003] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2007] [Revised: 12/27/2007] [Accepted: 01/02/2008] [Indexed: 11/27/2022]
Abstract
The effects of food deprivation and refeeding on daily rhythms of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and melatonin contents, as well as on arylalkylamine N-acetyltransferase (AANAT) activity were evaluated in the pineal organ of rainbow trout. In addition, changes in circulating melatonin and cortisol levels were tested at one single point at day and night. Immature rainbow trout were distributed in 3 experimental groups: fish fed, fish fasted (7 days), and fish fasted for 7 days and refed for 5 days. All fish were sampled from each treatment group at different times of the day-night cycle. Pineal melatonin levels and AANAT activity showed daily variations in either fed, fasted and refed trout, displaying highest values at night. Fasted trout showed reduced melatonin content throughout the 24-h cycle, which was associated with decreased AANAT activity. Rhythms of pineal 5-HT and 5-HIAA levels were evident in all groups and were negatively correlated to melatonin in fed fish groups, but not in fasted fish. A higher content of 5-HT and 5-HIAA was observed in fasted fish during the night with no apparent changes during daytime for 5-HT and increased 5-HIAA levels. Furthermore, decreased circulating levels of melatonin were observed at midday, but not at night, in food deprived trout. Refeeding for 5 days generally counteracted the effects of food deprivation. Cortisol levels in plasma were reduced after food deprivation and remained low in refed fish. The results show that food deprivation impairs daily rhythms of melatonin content in trout pineal organ by affecting the activity of melatonin synthesizing enzymes rather than by a deficiency in substrate availability.
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Affiliation(s)
- Rosa M Ceinos
- Departamento de Bioloxía Funcional e Ciencias da Saude, Edificio de Ciencias Experimentais, Facultade de Bioloxía, Universidade de Vigo, Vigo, Pontevedra, Spain
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Janecka IP. Colon Cancer and Physical Activity: A Content Analysis of Reciprocal Relationship. Clin Med Oncol 2007. [DOI: 10.4137/cmo.s299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Background Colon cancer is among the leading causes of cancer mortality and its incidence is increasing worldwide. This is true in spite of broad basic research into colon cancer while, concurrently, physical activity has been shown to offer significant preventive potential. This background led to the formulation of the following research questions: • Why is physical activity so effective in decreasing the incidence of colon cancer? • Is there a common denominator to colon cancer and physical activity, which has a reciprocal function? • Knowing the potential for public health impact of physical activity on colon cancer, has physical activity-colon cancer relationship been in the forefront of research efforts? Methods Content analysis of archival literature has been carried out on census of 32,822 message units, extracted from the National Library of Medicine and its PubMed database. The following search terms were used: colon cancer, physical activity, melatonin, age/genetics, diet (obesity, vitamin D, calcium), immunity/inflammation, and bioactive substances incorporating insulin-like growth factor 1, interleukins, and prostaglandins. The research timeframe for each category began with the first article published and ended with the last one printed in 2005. Results/Conclusions The effectiveness of physical activity in decreasing the incidence of colon cancer is likely the result of its biologic activity within not one or two but all of the major known colon cancer etiologies, demonstrating a powerful reciprocal relationship. Melatonin is identified as a plausible common denominator of colon cancer and physical activity. The greatest volume of publications deals with colon cancer and genetics. A significant societal health care impact could be achieved by adopting physical activity as a major cancer control strategy.
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Singh SS, Haldar C. Biological significance of daily variation in immunity ofPerdicula asiatica: role of melatonin and testosterone. BIOL RHYTHM RES 2007. [DOI: 10.1080/09291010600902652] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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Alqarawi AA, Elmougy SA. The existence of extrapineal locations for melatonin synthesis in the one-humped camel (Camelus dromedarius). BIOL RHYTHM RES 2007. [DOI: 10.1080/09291010600832289] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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López-Olmeda JF, Madrid JA, Sánchez-Vázquez FJ. Melatonin effects on food intake and activity rhythms in two fish species with different activity patterns: Diurnal (goldfish) and nocturnal (tench). Comp Biochem Physiol A Mol Integr Physiol 2006; 144:180-7. [PMID: 16580857 DOI: 10.1016/j.cbpa.2006.02.031] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2005] [Revised: 02/13/2006] [Accepted: 02/21/2006] [Indexed: 11/15/2022]
Abstract
Melatonin has several known physiological functions, the main one being synchronization of daily and seasonal rhythms. In addition, melatonin has been reported to influence food intake and behavioral rhythms with varying results depending on the species. The aim of this research was to evaluate the effects of intraperitoneal melatonin injection on food intake and locomotor activity in two different fish species: goldfish (diurnal) and tench (nocturnal), under different light regimes: constant light (LL) conditions or LD 12:12, with melatonin administration at mid-light (ML), mid-dark (MD), and after a 1-h light pulse at MD. In addition to these acute tests, in the case of goldfish we also investigated the effects of daily melatonin administration for 1 week. Our results indicated that acute melatonin administration significantly decreased goldfish food intake (16-52% inhibition, depending on the light regime) and locomotor activity (55-100%), with the chronic treatment inducing a similar total food intake inhibition that persisted for 7 days. In tench, a nocturnal fish species, acute melatonin administration at MD and ML reduced food intake (37% and 29%, respectively), while locomotor activity was not affected at MD and slightly increased at ML. Taken together, these results indicated that melatonin reduced food intake in both species, while its effects on locomotor activity depended on the time of administration (light or dark phase) and the activity patterns of the species.
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Affiliation(s)
- J F López-Olmeda
- Department of Physiology, Faculty of Biology, University of Murcia, 30100-Murcia, Spain.
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Selmaoui B, Thibault L. The induction of low nocturnal secretion of melatonin caused by reverse feeding rhythms depends on availability of macronutrient diets. Nutr Neurosci 2002; 5:417-26. [PMID: 12509071 DOI: 10.1080/1028415021000055961] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
The present study investigated the effect of single chow diet and two-way dietary choice between a protein-rich and a carbohydrate-rich diet ingested during free access or daytime access (08.00-16.00 h) on the rhythms of ingestion and on nocturnal levels of serum melatonin and pineal N-acetyltransferase activity in rats. Animals with free access to the single or the choice diets displayed a circadian rhythmicity of total food intake with peaks at the beginning, the middle and the end of the dark phase. Rats fed the dietary choice displayed a preference for carbohydrate at the beginning, and a preference for protein at the middle and the end of the dark phase. Under daytime feeding access, both dietary conditions resulted in only one peak of total intake at the beginning of the access period. Rats fed the choice diets on the daytime feeding schedule initially preferred carbohydrate to protein but this preference disappeared subsequently. Nocturnal peaks of serum melatonin and pineal NAT activity were lower with daytime access to dietary choice compared to ad libitum access. The results suggest that in a two-way selection of macronutrients, feeding cycle can directly act on the rhythms expressed within the pineal gland.
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Affiliation(s)
- B Selmaoui
- Laboratoire de chronobiologie, Hôpital du Sacré-Coeur de Montreal, 5400 Boulevard Gouin Ouest, Montréal, Que., Canada H4J 1C5
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Otsuka K, Cornélissen G, Halberg F. Circadian rhythms and clinical chronobiology. Biomed Pharmacother 2002; 55 Suppl 1:7s-18s. [PMID: 11774872 DOI: 10.1016/s0753-3322(01)90000-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Affiliation(s)
- K Otsuka
- Department of Medicine, Tokyo Women's Medical University, School of Medicine, Daini Hospital, Japan
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Otsuka K, Oinuma S, Cornélissen G, Weydahl A, Ichimaru Y, Kobayashi M, Yano S, Holmeslet B, Hansen TL, Mitsutake G, Engebretson MJ, Schwartzkopff O, Halberg F. Alternating light-darkness-influenced human electrocardiographic magnetoreception in association with geomagnetic pulsations. Biomed Pharmacother 2002; 55 Suppl 1:63s-75s. [PMID: 11774870 DOI: 10.1016/s0753-3322(01)90007-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Geomagnetic variations of partly interplanetary origin, with cyclic signatures in human affairs and pathology include the incidence of various diseases, regarding which this study of healthy subjects attempted to determine an underlying mechanism by worldwide archival and physiological monitoring, notably of heart rate variability (HRV). In the past half-century, the possible health and other hazards of natural, solar variability-driven temporal variations in the earth's magnetic field have become a controversial subject in view of the inconsistent results. Some well-documented claims of associations between geomagnetic storms and myocardial infarction or stroke have been rejected by a study based on more comprehensive data analyzed by rigorous methods - covering, however, only part of a solar cycle in only part of a hemisphere. It seems possible that inter-solar cycle and geographic variability, if not geographic differences, may account for discrepancies. Herein, we examine the start of a planetary study on any influence of geomagnetic disturbances that are most pronounced in the auroral oval, on human HRV. The magnetic field variations exhibit complex spectra and include the frequency band between 0.001-10 Hz, which is regarded as ultra-low frequency by physicists. Since the 'ultra-low-frequency' range, like other endpoints used in cardiology, refers to much higher frequencies than the about-yearly changes that are here shown to play a role in environmental-organismic interactions revealed by HRV, the current designations used in cardiology are all placed in quotation marks to indicate the need for possible revision. Whether or not this suggestion has an immediate response, we have pointed to a need for the development of instrumentation and software that renders the assessment of circadian, infradian and even infra-annual (truly low frequency) modulations routinely feasible. HRV was examined on the basis of nearly continuous 7-day records by ECG between December 10, 1998, and November 2, 2000, on 19 clinically healthy subjects, 21 to 54 years of age, in Alta, Norway. A geomagnetic record was obtained from the Auroral Observatory of the University of Tromsø. First, frequency-domain measures of HRV were compared for each person in 24-hour spans of high geomagnetic disturbance versus quiet conditions. Second, cross-spectra between geomagnetic activity and HRV measures were quantified via the squared coherence spectrum using 7-day time series. A 7.5% increase in the 24-hour average of heart rate, HR (P = 0.00020) and a decrease in HRV were documented on days of high geomagnetic disturbance. The decrease in HRV was validated statistically for the 'total frequency', 'TF' endpoint (18.6% decrease, P= 0.00009). The decrease in spectral power was found primarily in the 'circaminutan frequency', 'VLF' (21.9% decrease, P< 0.000001) in conjunction with the 'minutes-to-hours' component, ultra-low-frequency, 'ULF' (15.5% decrease, P= 0.00865) and circadecasecundan 'low frequency', 'LF' (14.2% decrease, P = 0.00187) regions of the spectrum. Power-law scaling of the power spectra did not show any statistically significant difference. It is noteworthy that most of the decrease in HRV, except for the circaminutan (VLF) component, was observed only in the season in which sunshine alternated with darkness (D/L), a finding suggesting a mechanism influenced by the alternation of light and darkness. The hypothesis of a light-dark-influenced magnetoreception was also supported by cross-spectral analysis. Group-averaged coherence at frequencies coincident with the geomagnetic Pc 6 pulsations (with periods ranging from 10 minutes to 5 hours) differed with a statistical significance (P < 0.000001) among the three natural lighting conditions, the association being weaker during UL or D/D than during D/L. By contrast, no statistically significant differences were found in terms of the circadian and circasemidian frequencies in relation to the alternation of sunshine with darkness or rather circannual rhythm stage. In conclusion, evidence is provided herein that an alteration of HRV is most apparent in the circaminutan ('VLF') region, which is clinically important, because a reduction in its power is a predictor of morbidity and mortality from cardiovascular disease. The circadecasecundan ('LF') component of HRV also decreased in association with geomagnetic disturbance, which may reflect an episodic alteration of arterial pressure related to changes in geomagnetic activity. Lastly, our study suggests the existence of a light-dark-influenced magnetoreception mechanism in humans involving mainly the Pc 6 band of the magnetic field.
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Affiliation(s)
- K Otsuka
- Department of Medicine, Tokyo Women's Medical University, School of Medicine, Daini Hospital, Nishiogu, Japan.
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