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Tang W, Long Z, Xiao Y, Du J, Tang C, Chen J, Hou C. Dietary butyric acid intake, kidney function, and survival: The National Health and Nutrition Examination Surveys, 2005-2018. Clin Nutr ESPEN 2025; 67:453-462. [PMID: 40147762 DOI: 10.1016/j.clnesp.2025.03.011] [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: 05/15/2024] [Revised: 02/23/2025] [Accepted: 03/10/2025] [Indexed: 03/29/2025]
Abstract
BACKGROUND Although preclinical data support the hypothesis that butyric acid supplementation improves kidney health, the clinical significance of dietary butyric acid intake in patients with chronic kidney disease (CKD) remains unconfirmed in large-sample studies. This study aimed to investigate the association between dietary butyric acid intake and all-cause mortality in the United States population, stratified by kidney function. METHODS We examined the relationship between dietary butyric acid intake, assessed through a 24-h dietary recall, and all-cause mortality among 23,008 consecutive adult participants from the National Health and Nutrition Examination Surveys (NHANES, 2005-2018), categorized by impaired versus normal kidney function (estimated glomerular filtration rate <60 vs ≥ 60 mL/min/1.72 m2), using multivariable Cox models. We also employed a restricted cubic spline based on Cox regression models to elucidate the nonlinear relationship between dietary butyric acid intake and mortality in patients. RESULT In participants with impaired kidney function, high dietary butyric acid intake was associated with lower mortality, while lower intake levels (reference) showed no such association: adjusted HRs (aHRs) were 0.67 (95 % CI: 0.45, 1.00), 0.65 (95 % CI: 0.45, 0.94), and 0.58 (95 % CI: 0.38, 0.89) for intake levels of the square root of butyric acid 0.25-0.45, 0.45-0.75, and >0.75 g/day, respectively. However, in participants with normal kidney function, no association between butyric acid levels and mortality was observed. Additionally, we identified an L-shaped association between the levels of the square root of dietary butyric acid intake and all-cause mortality in the CKD population, reaching a plateau at 0.52 g/day (butyric acid intake of approximately 0.27 g/day). CONCLUSION This study revealed a nonlinear association between high dietary butyric acid intake and reduced all-cause mortality in patients with chronic kidney disease. A plateau occurs after 0.27 g/day, and for individuals with CKD whose butyric acid intake is below approximately 0.27 g/day, increasing a butyrate-rich diet or supplementing with butyric acid preparations may help prevent progression to renal failure and associated adverse outcomes in CKD patients, thereby reducing mortality. Therefore, it can be considered a new therapeutic strategy for the treatment of chronic kidney disease.
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Affiliation(s)
- Wei Tang
- Hunan Key Laboratory of Kidney Disease and Blood Purification, and Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zhengyi Long
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Yang Xiao
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Jingyun Du
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Chenyuan Tang
- Hunan Key Laboratory of Kidney Disease and Blood Purification, and Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - JunXiang Chen
- Hunan Key Laboratory of Kidney Disease and Blood Purification, and Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
| | - Can Hou
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
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Diep TN, Liu H, Yan LJ. Beneficial Effects of Butyrate on Kidney Disease. Nutrients 2025; 17:772. [PMID: 40077642 PMCID: PMC11901450 DOI: 10.3390/nu17050772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 02/13/2025] [Accepted: 02/17/2025] [Indexed: 03/14/2025] Open
Abstract
The gut microbiota influences and contributes to kidney health and disease. Butyrate, a short-chain fatty acid molecule generated via the fermentation of gut bacterial catabolism of nondigestible dietary fiber, has been shown to exert numerous beneficial effects on kidney disorders. The objective of this review was to discuss the latest findings on the protective effects of butyrate on a variety of animal models of kidney injury. We conducted a PubMed search using the title word "butyrate" and keyword "kidney" to generate our literature review sources. The animal models covered in this review include ischemia-reperfusion renal injury, cisplatin- and folic acid-induced kidney injury, septic kidney injury, diabetic kidney disease (DKD), high-fat diet (HFD)-induced glomerulopathy, adenine-induced chronic kidney disease (CKD), high-salt-induced renal injury, and T-2 toxin-induced kidney injury in birds. The protective mechanisms of butyrate that are most shared among these animal model studies include antioxidative stress, anti-fibrosis, anti-inflammation, and anti-cell death. This review ends with suggestions for future studies on potential approaches that may modulate gut microbiota butyrate production for the well-being of kidneys with the kidney disorders covered in this review.
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Affiliation(s)
| | | | - Liang-Jun Yan
- Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA; (T.N.D.); (H.L.)
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Allan NP, Yamamoto BY, Kunihiro BP, Nunokawa CKL, Rubas NC, Wells RK, Umeda L, Phankitnirundorn K, Torres A, Peres R, Takahashi E, Maunakea AK. Ketogenic Diet Induced Shifts in the Gut Microbiome Associate with Changes to Inflammatory Cytokines and Brain-Related miRNAs in Children with Autism Spectrum Disorder. Nutrients 2024; 16:1401. [PMID: 38794639 PMCID: PMC11124410 DOI: 10.3390/nu16101401] [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: 04/04/2024] [Revised: 05/01/2024] [Accepted: 05/01/2024] [Indexed: 05/26/2024] Open
Abstract
In this interventional pilot study, we investigated the effects of a modified ketogenic diet (KD) on children with autism spectrum disorder (ASD). We previously observed improved behavioral symptoms in this cohort following the KD; this trial was registered with Clinicaltrials.gov (NCT02477904). This report details the alterations observed in the microbiota, inflammation markers, and microRNAs of seven children following a KD for a duration of 4 months. Our analysis included blood and stool samples, collected before and after the KD. After 4 months follow up, we found that the KD led to decreased plasma levels of proinflammatory cytokines (IL-12p70 and IL-1b) and brain-derived neurotrophic factor (BDNF). Additionally, we observed changes in the gut microbiome, increased expression of butyrate kinase in the gut, and altered levels of BDNF-associated miRNAs in the plasma. These cohort findings suggest that the KD may positively influence ASD sociability, as previously observed, by reducing inflammation, reversing gut microbial dysbiosis, and impacting the BDNF pathway related to brain activity.
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Affiliation(s)
- Nina P. Allan
- Department of Biochemistry, Anatomy, and Physiology, University of Hawai’i at Mānoa, Honolulu, HI 96822, USA; (N.P.A.); (B.Y.Y.); (B.P.K.); (C.K.L.N.); (N.C.R.); (R.K.W.); (L.U.); (K.P.); (A.T.); (R.P.)
| | - Brennan Y. Yamamoto
- Department of Biochemistry, Anatomy, and Physiology, University of Hawai’i at Mānoa, Honolulu, HI 96822, USA; (N.P.A.); (B.Y.Y.); (B.P.K.); (C.K.L.N.); (N.C.R.); (R.K.W.); (L.U.); (K.P.); (A.T.); (R.P.)
| | - Braden P. Kunihiro
- Department of Biochemistry, Anatomy, and Physiology, University of Hawai’i at Mānoa, Honolulu, HI 96822, USA; (N.P.A.); (B.Y.Y.); (B.P.K.); (C.K.L.N.); (N.C.R.); (R.K.W.); (L.U.); (K.P.); (A.T.); (R.P.)
| | - Chandler K. L. Nunokawa
- Department of Biochemistry, Anatomy, and Physiology, University of Hawai’i at Mānoa, Honolulu, HI 96822, USA; (N.P.A.); (B.Y.Y.); (B.P.K.); (C.K.L.N.); (N.C.R.); (R.K.W.); (L.U.); (K.P.); (A.T.); (R.P.)
| | - Noelle C. Rubas
- Department of Biochemistry, Anatomy, and Physiology, University of Hawai’i at Mānoa, Honolulu, HI 96822, USA; (N.P.A.); (B.Y.Y.); (B.P.K.); (C.K.L.N.); (N.C.R.); (R.K.W.); (L.U.); (K.P.); (A.T.); (R.P.)
- Molecular Biosciences and Bioengineering, College of Tropical Agriculture and Human Resources, University of Hawai’i at Manoa, Honolulu, HI 96822, USA
| | - Riley K. Wells
- Department of Biochemistry, Anatomy, and Physiology, University of Hawai’i at Mānoa, Honolulu, HI 96822, USA; (N.P.A.); (B.Y.Y.); (B.P.K.); (C.K.L.N.); (N.C.R.); (R.K.W.); (L.U.); (K.P.); (A.T.); (R.P.)
- Molecular Biosciences and Bioengineering, College of Tropical Agriculture and Human Resources, University of Hawai’i at Manoa, Honolulu, HI 96822, USA
| | - Lesley Umeda
- Department of Biochemistry, Anatomy, and Physiology, University of Hawai’i at Mānoa, Honolulu, HI 96822, USA; (N.P.A.); (B.Y.Y.); (B.P.K.); (C.K.L.N.); (N.C.R.); (R.K.W.); (L.U.); (K.P.); (A.T.); (R.P.)
- Molecular Biosciences and Bioengineering, College of Tropical Agriculture and Human Resources, University of Hawai’i at Manoa, Honolulu, HI 96822, USA
| | - Krit Phankitnirundorn
- Department of Biochemistry, Anatomy, and Physiology, University of Hawai’i at Mānoa, Honolulu, HI 96822, USA; (N.P.A.); (B.Y.Y.); (B.P.K.); (C.K.L.N.); (N.C.R.); (R.K.W.); (L.U.); (K.P.); (A.T.); (R.P.)
| | - Amada Torres
- Department of Biochemistry, Anatomy, and Physiology, University of Hawai’i at Mānoa, Honolulu, HI 96822, USA; (N.P.A.); (B.Y.Y.); (B.P.K.); (C.K.L.N.); (N.C.R.); (R.K.W.); (L.U.); (K.P.); (A.T.); (R.P.)
| | - Rafael Peres
- Department of Biochemistry, Anatomy, and Physiology, University of Hawai’i at Mānoa, Honolulu, HI 96822, USA; (N.P.A.); (B.Y.Y.); (B.P.K.); (C.K.L.N.); (N.C.R.); (R.K.W.); (L.U.); (K.P.); (A.T.); (R.P.)
| | - Emi Takahashi
- Department of Radiology, Harvard Medical School, Boston, MA 02115, USA;
- Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA 02129, USA
| | - Alika K. Maunakea
- Department of Biochemistry, Anatomy, and Physiology, University of Hawai’i at Mānoa, Honolulu, HI 96822, USA; (N.P.A.); (B.Y.Y.); (B.P.K.); (C.K.L.N.); (N.C.R.); (R.K.W.); (L.U.); (K.P.); (A.T.); (R.P.)
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Zhou M, Ma J, Kang M, Tang W, Xia S, Yin J, Yin Y. Flavonoids, gut microbiota, and host lipid metabolism. Eng Life Sci 2024; 24:2300065. [PMID: 38708419 PMCID: PMC11065335 DOI: 10.1002/elsc.202300065] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 08/19/2023] [Accepted: 08/30/2023] [Indexed: 05/07/2024] Open
Abstract
Flavonoids are widely distributed in nature and have a variety of beneficial biological effects, including antioxidant, anti-inflammatory, and anti-obesity effects. All of these are related to gut microbiota, and flavonoids also serve as a bridge between the host and gut microbiota. Flavonoids are commonly used to modify the composition of the gut microbiota by promoting or inhibiting specific microbial species within the gut, as well as modifying their metabolites. In turn, the gut microbiota extensively metabolizes flavonoids. Hence, this reciprocal relationship between flavonoids and the gut microbiota may play a crucial role in maintaining the balance and functionality of the metabolism system. In this review, we mainly highlighted the biological effects of antioxidant, anti-inflammatory and antiobesity, and discussed the interaction between flavonoids, gut microbiota and lipid metabolism, and elaborated the potential mechanisms on host lipid metabolism.
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Affiliation(s)
- Miao Zhou
- College of Animal Science and TechnologyHunan Agricultural UniversityChangshaChina
| | - Jie Ma
- College of Animal Science and TechnologyHunan Agricultural UniversityChangshaChina
| | - Meng Kang
- College of Animal Science and TechnologyHunan Agricultural UniversityChangshaChina
| | - Wenjie Tang
- Sichuan Animal Science AcademyLivestock and Poultry Biological Products Key Laboratory of Sichuan ProvinceSichuan Animtech Feed Co., LtdChengduSichuanChina
| | - Siting Xia
- College of Animal Science and TechnologyHunan Agricultural UniversityChangshaChina
| | - Jie Yin
- College of Animal Science and TechnologyHunan Agricultural UniversityChangshaChina
| | - Yulong Yin
- College of Animal Science and TechnologyHunan Agricultural UniversityChangshaChina
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Dou X, Yan D, Liu S, Gao N, Ma Z, Shi Z, Dong N, Shan A. Host Defense Peptides in Nutrition and Diseases: A Contributor of Immunology Modulation. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:3125-3140. [PMID: 36753427 DOI: 10.1021/acs.jafc.2c08522] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/18/2023]
Abstract
Host defense peptides (HDPs) are primary components of the innate immune system with diverse biological functions, such as antibacterial ability and immunomodulatory function. HDPs are produced and released by immune and epithelial cells against microbial invasion, which are widely distributed in humans, animals, plants, and microbes. Notably, there are great differences in endogenous HDP distribution and expression in humans and animals. Moreover, HDP expression could be regulated by exogenous substances, such as nutrients, and different physiological statuses in health and disease. In this review, we systematically assessed the regulation of expression and mechanism of endogenous HDPs from nutrition and disease perspectives, providing a basis to identify the specificity and regularity of HDP expression. Furthermore, the regulation mechanism of HDP expression was summarized systematically, and the differences in the regulation between nutrients and diseases were explored. From this review, we provide novel ideas targeted the immune regulation of HDPs for protecting host health in nutrition and practical and effective new ideas using the immune regulation theory for further research on protecting host health from pathogenic infection and excessive immunity diseases under the global challenge of the antibiotic-abuse-induced series of problems, including food security and microbial resistance.
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Affiliation(s)
- Xiujing Dou
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, Heilongjiang 150030, People's Republic of China
| | - Di Yan
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, Heilongjiang 150030, People's Republic of China
| | - Siqi Liu
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, Heilongjiang 150030, People's Republic of China
| | - Nan Gao
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, Heilongjiang 150030, People's Republic of China
| | - Ziwen Ma
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, Heilongjiang 150030, People's Republic of China
| | - Zixuan Shi
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, Heilongjiang 150030, People's Republic of China
| | - Na Dong
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, Heilongjiang 150030, People's Republic of China
| | - Anshan Shan
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, Heilongjiang 150030, People's Republic of China
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Gao N, Yang Y, Liu S, Fang C, Dou X, Zhang L, Shan A. Gut-Derived Metabolites from Dietary Tryptophan Supplementation Quench Intestinal Inflammation through the AMPK-SIRT1-Autophagy Pathway. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:16080-16095. [PMID: 36521060 DOI: 10.1021/acs.jafc.2c05381] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
Tryptophan has drawn wide attention due to its involvement in improving intestinal immune defense directly and indirectly by regulating metabolic pathways. The study aims to elucidate the potential modulating roles of tryptophan to protect against intestinal inflammation and elucidate the underlying molecular mechanisms. The protective effects of tryptophan against intestinal inflammation are examined in the lipopolysaccharide (LPS)-induced inflammatory model. We first found that tryptophan markedly (p < 0.01) inhibited proinflammatory cytokines production and nuclear factor κB (NF-κB) pathway activation upon LPS challenge. Next, we demonstrated that tryptophan (p < 0.05) attenuated LPS-caused intestinal mucosal barrier damage by increasing the number of goblet cells, mucins, and antimicrobial peptides (AMPs) in the ileum of mice. In addition, tryptophan (p < 0.05) inhibited LPS-induced autophagic flux through the AMP-activated protein kinase (AMPK)-sirtuin 1 (SIRT1) pathway in the intestinal systems to maintain autophagy homeostasis. Meanwhile, tryptophan also reshaped the gut microbiota composition in LPS-challenge mice by increasing the abundance of short-chain fatty acid (SCFA)-producing bacteria such as Acetivibrio (0.053 ± 0.017 to 0.21 ± 0.0041%). Notably, dietary tryptophan resulted in the activation of metabolic pathways during the inflammatory response. Furthermore, exogenous treatment of tryptophan metabolites kynurenine (Kyn) and 5-HT in porcine intestinal epithelial cells (IPEC-J2 cells) reproduced similar protective effects as tryptophan to attenuate LPS-induced intestinal inflammation through regulating the AMPK-SIRT1-autophagy. Taken together, the present study indicates that tryptophan exhibits intestinal protective and immunoregulatory effects resulting from the activation of metabolic pathways, maintenance of gut mucosal barrier integrity, microbiota composition, and AMPK-SIRT1-autophagy level.
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Affiliation(s)
- Nan Gao
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
| | - Yang Yang
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
| | - Siqi Liu
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
| | - Chunyang Fang
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
| | - Xiujing Dou
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
| | - Licong Zhang
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
| | - Anshan Shan
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
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Cheng X, Zhou T, He Y, Xie Y, Xu Y, Huang W. The role and mechanism of butyrate in the prevention and treatment of diabetic kidney disease. Front Microbiol 2022; 13:961536. [PMID: 36016798 PMCID: PMC9396028 DOI: 10.3389/fmicb.2022.961536] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Accepted: 07/25/2022] [Indexed: 11/13/2022] Open
Abstract
Diabetic kidney disease (DKD) remains the leading cause of the end-stage renal disease and is a major burden on the healthcare system. The current understanding of the mechanisms responsible for the progression of DKD recognizes the involvement of oxidative stress, low-grade inflammation, and fibrosis. Several circulating metabolites that are the end products of the fermentation process, released by the gut microbiota, are known to be associated with systemic immune-inflammatory responses and kidney injury. This phenomenon has been recognized as the “gut–kidney axis.” Butyrate is produced predominantly by gut microbiota fermentation of dietary fiber and undigested carbohydrates. In addition to its important role as a fuel for colonic epithelial cells, butyrate has been demonstrated to ameliorate obesity, diabetes, and kidney diseases via G-protein coupled receptors (GPCRs). It also acts as an epigenetic regulator by inhibiting histone deacetylase (HDAC), up-regulation of miRNAs, or induction of the histone butyrylation and autophagy processes. This review aims to outline the existing literature on the treatment of DKD by butyrate in animal models and cell culture experiments, and to explore the protective effects of butyrate on DKD and the underlying molecular mechanism.
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Affiliation(s)
- Xi Cheng
- Department of Endocrinology and Metabolism, Metabolic Vascular Diseases Key Laboratory of Sichuan Province, Affiliated Hospital of Southwest Medical University, Luzhou, China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, China
- Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, China
| | - Tingting Zhou
- Department of Endocrinology and Metabolism, Metabolic Vascular Diseases Key Laboratory of Sichuan Province, Affiliated Hospital of Southwest Medical University, Luzhou, China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, China
- Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, China
- Tingting Zhou,
| | - Yanqiu He
- Department of Endocrinology and Metabolism, Metabolic Vascular Diseases Key Laboratory of Sichuan Province, Affiliated Hospital of Southwest Medical University, Luzhou, China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, China
- Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, China
| | - Yumei Xie
- Sichuan Clinical Research Center for Nephropathy, Luzhou, China
| | - Yong Xu
- Department of Endocrinology and Metabolism, Metabolic Vascular Diseases Key Laboratory of Sichuan Province, Affiliated Hospital of Southwest Medical University, Luzhou, China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, China
- Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, China
- *Correspondence: Yong Xu,
| | - Wei Huang
- Department of Endocrinology and Metabolism, Metabolic Vascular Diseases Key Laboratory of Sichuan Province, Affiliated Hospital of Southwest Medical University, Luzhou, China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, China
- Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, China
- Wei Huang,
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Dou X, Yan D, Liu S, Gao L, Shan A. Thymol Alleviates LPS-Induced Liver Inflammation and Apoptosis by Inhibiting NLRP3 Inflammasome Activation and the AMPK-mTOR-Autophagy Pathway. Nutrients 2022; 14:nu14142809. [PMID: 35889766 PMCID: PMC9319298 DOI: 10.3390/nu14142809] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 07/05/2022] [Accepted: 07/06/2022] [Indexed: 01/17/2023] Open
Abstract
Thymol is a natural antibacterial agent found in the essential oil extracted from thyme, which has been proven to be beneficial in food and medicine. Meanwhile, the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and autophagy have been reported to play key roles in the progression of liver injury. However, the effects of thymol on the NLRP3 inflammasome and autophagy in protecting the liver remain unclear. The present study used a mouse model with liver injury induced by lipopolysaccharides (LPS) to investigate the regulatory mechanisms of thymol. We found that thymol alleviated LPS-induced liver structural damage, as judged by reduced inflammatory cell infiltration and improved structure. In addition, elevated levels of the liver damage indicators (alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin (TBIL)) dropped after thymol administration. The mRNA and protein expression of inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-22), apoptosis-related genes (caspase3 and caspase9), and the activity of apoptosis-related genes (caspase3 and caspase9) were increased in LPS-treated livers, whereas the changes were alleviated after thymol administration. Thymol inhibited LPS-induced increment in lactate dehydrogenase (LDH) activity in primary hepatocytes of the mouse. In addition, thymol protected mice from liver injury by inhibiting NLRP3 inflammasome activation induced by LPS. Mechanistically, the present study indicates that thymol has liver protective activity resulting from the modulation of the AMP-activated protein kinase—mammalian target of rapamycin (AMPK–mTOR) to regulate the autophagy pathway, hence curbing inflammation.
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Alleviation of Oral Exposure to Aflatoxin B1-Induced Renal Dysfunction, Oxidative Stress, and Cell Apoptosis in Mice Kidney by Curcumin. Antioxidants (Basel) 2022; 11:antiox11061082. [PMID: 35739979 PMCID: PMC9219944 DOI: 10.3390/antiox11061082] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Revised: 05/23/2022] [Accepted: 05/27/2022] [Indexed: 02/06/2023] Open
Abstract
Aflatoxin B1 is a contaminant widely found in food and livestock feed, posing a major threat to human and animal health. Recently, much attention from the pharmaceutical and food industries has been focused on curcumin due to its strong antioxidant capacity. However, the therapeutic impacts and potential mechanisms of curcumin on kidney damage caused by AFB1 are still incomplete. In this study, AFB1 triggered renal injury in mice, as reflected by pathological changes and renal dysfunction. AFB1 induced renal oxidative stress and interfered with the Keap1–Nrf2 pathway and its downstream genes (CAT, SOD1, NQO1, GSS, GCLC, and GCLM), as manifested by elevated oxidative stress metabolites and reduced antioxidant enzymes activities. Additionally, AFB1 was found to increase apoptotic cells percentage in the kidney via the TUNEL assay, along with increased expression of Cyt-c, Bax, cleaved-Caspase-3, Caspase-9, and decreased expression of Bcl-2 at the transcriptional and protein levels; in contrast, for mice given curcumin, there was a significant reversal in kidney coefficient, biochemical parameters, pathological changes, and the expression of genes and proteins involved in oxidative stress and apoptosis. These results indicate that curcumin could antagonize oxidative stress and apoptosis to attenuate AFB1-induced kidney damage.
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Zhang M, Jiao P, Wang X, Sun Y, Liang G, Xie X, Zhang Y. Evaluation of Growth Performance, Nitrogen Balance and Blood Metabolites of Mutton Sheep Fed an Ammonia-Treated Aflatoxin B1-Contaminated Diet. Toxins (Basel) 2022; 14:toxins14050361. [PMID: 35622607 PMCID: PMC9144722 DOI: 10.3390/toxins14050361] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 05/18/2022] [Accepted: 05/19/2022] [Indexed: 12/11/2022] Open
Abstract
Experiments were conducted to evaluate the effects of an aflatoxin B1 (AFB1)-contaminated diet treated with ammonia on the diet detoxification and growth performance, nutrient digestibility, nitrogen utilization, and blood metabolites in sheep. Twenty-four female mutton sheep with an initial body weight of 50 ± 2.5 kg were randomly assigned to one of three groups: (1) control diet (C); (2) aflatoxin diet (T; control diet supplemented with 75 μg of AFB1/kg of dry matter); and (3) ammoniated diet (AT; ammoniated aflatoxin diet). The results showed decreases (p < 0.05) in average daily feed intake, nutrient digestibility of dry matter, crude protein and ether extract, and retained nitrogen, and an increase (p < 0.05) in urine nitrogen excretion in sheep fed diet T compared with those fed the other diets. In comparison to C and AT, feeding T decreased (p < 0.05) the concentrations of total protein, immunoglobulin A, immunoglobulin G, immunoglobulin M, superoxide dismutase, and total antioxidants and increased (p < 0.05) the concentrations of alanine amino transferase, malondialdehyde, and interleukin-6. In summary, ammonia treatment has the potential to decrease the concentration of AFB1 and alleviate the adverse effects of AFB1.
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