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Morad M, Hassanein T, El-khadragy M, Fehaid A, Habotta O, Abdel Moneim A. Biochemical and histopathological effects of copper oxide nanoparticles exposure on the bivalve Chambardia rubens (Lamarck, 1819). Biosci Rep 2023; 43:BSR20222308. [PMID: 37128859 PMCID: PMC10196149 DOI: 10.1042/bsr20222308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 04/26/2023] [Accepted: 04/27/2023] [Indexed: 05/03/2023] Open
Abstract
Copper nanoparticles are widely incorporated into many applications, including air and liquid filters, wood preservatives, batteries, thermal and electrical conductivity, inks and skin products. Their potential toxicity and environmental fate, however, are poorly studied in the freshwater bivalves. The aim of the present study was to evaluate the different effects of copper oxide nanoparticles and ionic copper on the digestive glands and gills of the mussel Chambardia rubens. Mussels were treated with 100 and 1000 µg Cu L-1 of copper oxide nanoparticles (CuONPs) or ionic copper (Cu2+) for 3, 7, and 14 days. The Cu accumulation and markers of oxidative stress in the digestive glands and gills were evaluated. The results show that the digestive gland collected higher levels of the two forms of copper than the gills. Exposure to CuONPs or Cu2+ induced significant elevations in superoxide dismutase, glutathione peroxidase and lipid peroxidation. Notably, a significant decrease was observed in the glutathione levels after exposure to both copper forms. CuONPs only induced a significant increase in glutathione reductase and glutathione S-transferase. The ionic copper only induced a significant decrease in catalase activities in the gill tissues. Overall, CuONPs and Cu2+ provoked oxidative stress, and further research is needed to clarify their genotoxic and neurotoxic effects on freshwater mussels and other biota.
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Affiliation(s)
- Mostafa Morad
- Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo 11795, Egypt
| | - Taha F. Hassanein
- Department of Chemistry, Faculty of Science, Helwan University, Cairo 11795, Egypt
| | - Manal F. El-khadragy
- Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia
| | - Alaa Fehaid
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Mansoura University, Dakahlia, Egypt
| | - Ola A. Habotta
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Mansoura University, Dakahlia, Egypt
| | - Ahmed Abdel Moneim
- Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo 11795, Egypt
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Jung S, Zimin PI, Woods CB, Kayser EB, Haddad D, Reczek CR, Nakamura K, Ramirez JM, Sedensky MM, Morgan PG. Isoflurane inhibition of endocytosis is an anesthetic mechanism of action. Curr Biol 2022; 32:3016-3032.e3. [PMID: 35688155 PMCID: PMC9329204 DOI: 10.1016/j.cub.2022.05.037] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 03/30/2022] [Accepted: 05/13/2022] [Indexed: 10/18/2022]
Abstract
The mechanisms of volatile anesthetic action remain among the most perplexing mysteries of medicine. Across phylogeny, volatile anesthetics selectively inhibit mitochondrial complex I, and they also depress presynaptic excitatory signaling. To explore how these effects are linked, we studied isoflurane effects on presynaptic vesicle cycling and ATP levels in hippocampal cultured neurons from wild-type and complex I mutant (Ndufs4(KO)) mice. To bypass complex I, we measured isoflurane effects on anesthetic sensitivity in mice expressing NADH dehydrogenase (NDi1). Endocytosis in physiologic concentrations of glucose was delayed by effective behavioral concentrations of isoflurane in both wild-type (τ [unexposed] 44.8 ± 24.2 s; τ [exposed] 116.1 ± 28.1 s; p < 0.01) and Ndufs4(KO) cultures (τ [unexposed] 67.6 ± 16.0 s; τ [exposed] 128.4 ± 42.9 s; p = 0.028). Increasing glucose, to enhance glycolysis and increase ATP production, led to maintenance of both ATP levels and endocytosis (τ [unexposed] 28.0 ± 14.4; τ [exposed] 38.2 ± 5.7; reducing glucose worsened ATP levels and depressed endocytosis (τ [unexposed] 85.4 ± 69.3; τ [exposed] > 1,000; p < 0.001). The block in recycling occurred at the level of reuptake of synaptic vesicles into the presynaptic cell. Expression of NDi1 in wild-type mice caused behavioral resistance to isoflurane for tail clamp response (EC50 Ndi1(-) 1.27% ± 0.14%; Ndi1(+) 1.55% ± 0.13%) and halothane (EC50 Ndi1(-) 1.20% ± 0.11%; Ndi1(+) 1.46% ± 0.10%); expression of NDi1 in neurons improved hippocampal function, alleviated inhibition of presynaptic recycling, and increased ATP levels during isoflurane exposure. The clear alignment of cell culture data to in vivo phenotypes of both isoflurane-sensitive and -resistant mice indicates that inhibition of mitochondrial complex I is a primary mechanism of action of volatile anesthetics.
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Affiliation(s)
- Sangwook Jung
- Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA
| | - Pavel I Zimin
- Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA 98195, USA
| | - Christian B Woods
- Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA
| | - Ernst-Bernhard Kayser
- Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA
| | - Dominik Haddad
- Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
| | - Colleen R Reczek
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
| | - Ken Nakamura
- Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, CA 94158, USA
| | - Jan-Marino Ramirez
- Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA; Department of Neurological Surgery, University of Washington, Seattle, WA 98105, USA
| | - Margaret M Sedensky
- Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA 98195, USA
| | - Philip G Morgan
- Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA 98195, USA.
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Radiation-induced oxidative injury of the ileum and colon is alleviated by glucagon-like peptide-1 and -2. JOURNAL OF RADIATION RESEARCH AND APPLIED SCIENCES 2019. [DOI: 10.1016/j.jrras.2015.01.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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Carrillo W, Monteiro KM, Martínez-Maqueda D, Ramos M, Recio I, Carvalho JED. Antiulcerative Activity of Milk Proteins Hydrolysates. J Med Food 2018; 21:408-415. [PMID: 29216438 DOI: 10.1089/jmf.2017.0087] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Affiliation(s)
- Wilman Carrillo
- Research Institute of Food Science (CIAL), (CSIC-UAM), Cantoblanco Campus, Autonomous University of Madrid, Madrid, Spain
- Laboratory of Functional Foods, Faculty of Foods Science and Engineering, Technical University of Ambato, Ambato, Ecuador
- Research Department Faculty of Health and Human Sciences, Bolivar State University, Guaranda, Ecuador
| | | | - Daniel Martínez-Maqueda
- Research Institute of Food Science (CIAL), (CSIC-UAM), Cantoblanco Campus, Autonomous University of Madrid, Madrid, Spain
| | - Mercedes Ramos
- Research Institute of Food Science (CIAL), (CSIC-UAM), Cantoblanco Campus, Autonomous University of Madrid, Madrid, Spain
| | - Isidra Recio
- Research Institute of Food Science (CIAL), (CSIC-UAM), Cantoblanco Campus, Autonomous University of Madrid, Madrid, Spain
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Souza LKM, Araújo TS, Sousa NA, Sousa FBM, Nogueira KM, Nicolau LA, Medeiros JVR. Evidence that d-cysteine protects mice from gastric damage via hydrogen sulfide produced by d-amino acid oxidase. Nitric Oxide 2017; 64:1-6. [DOI: 10.1016/j.niox.2017.01.010] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Revised: 01/08/2017] [Accepted: 01/23/2017] [Indexed: 12/13/2022]
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da Rocha CQ, de-Faria FM, Marcourt L, Ebrahimi SN, Kitano BT, Ghilardi AF, Luiz Ferreira A, de Almeida ACA, Dunder RJ, Souza-Brito ARM, Hamburger M, Vilegas W, Queiroz EF, Wolfender JL. Gastroprotective effects of hydroethanolic root extract of Arrabidaea brachypoda: Evidences of cytoprotection and isolation of unusual glycosylated polyphenols. PHYTOCHEMISTRY 2017; 135:93-105. [PMID: 28010885 DOI: 10.1016/j.phytochem.2016.12.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/13/2016] [Revised: 11/23/2016] [Accepted: 12/02/2016] [Indexed: 06/06/2023]
Abstract
The hydroethanolic root extract of Arrabidaea brachypoda, from Bignoniaceae family, a Brazilian medicinal plant, demonstrated significant in vivo gastroprotective effects using different in vivo assays. The activity was evaluated in several models of experimental gastric ulcer in rats (absolute ethanol, glutathione depletion, nitric oxide depletion, non-steroidal anti-inflammatory drugs, pylorus ligation and acetic acid). Using 300 mg/kg (p.o.) the extract significantly reduced gastric injury in all models. In depth phytochemical investigation of this extract led to the isolation of two previously undescribed phenylethanoid glycosides derivatives and seven unusual glycosylated dimeric flavonoids. The structures were elucidated using UV, NMR and HRMS analysis. Absolute configuration of the dimeric flavonoids was performed by electronic circular dichroism (ECD) spectroscopy.
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Affiliation(s)
- Claudia Quintino da Rocha
- Institute of Biosciences, Coastal Campus of São Vicente, Universidade Estadual Paulista-UNESP, 11330-900, São Vicente, SP, Brazil; School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Centre Medical Universitaire-CMU, Rue Michel-Servet 1, CH-1211, Geneva 4, Switzerland
| | - Felipe Meira de-Faria
- Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas-UNICAMP, 13083-970, Campinas, SP, Brazil; Department of Structural and Functional Biology, Institute of Biology, State University of Campinas-UNICAMP, 13083-970, Campinas, SP, Brazil
| | - Laurence Marcourt
- School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Centre Medical Universitaire-CMU, Rue Michel-Servet 1, CH-1211, Geneva 4, Switzerland
| | - Samad Nejad Ebrahimi
- Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, Tehran, Iran
| | - Bruna Tiemi Kitano
- Department of Structural and Functional Biology, Institute of Biology, State University of Campinas-UNICAMP, 13083-970, Campinas, SP, Brazil
| | - Amanda Franceschini Ghilardi
- Department of Structural and Functional Biology, Institute of Biology, State University of Campinas-UNICAMP, 13083-970, Campinas, SP, Brazil
| | - Anderson Luiz Ferreira
- Department of Structural and Functional Biology, Institute of Biology, State University of Campinas-UNICAMP, 13083-970, Campinas, SP, Brazil; Nucleus of Biological Sciences, Institute of Biotechnology, Federal University of Goias, 75704-020, Catalão, GO, Brazil
| | - Ana Cristina Alves de Almeida
- Department of Structural and Functional Biology, Institute of Biology, State University of Campinas-UNICAMP, 13083-970, Campinas, SP, Brazil
| | - Ricardo José Dunder
- Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas-UNICAMP, 13083-970, Campinas, SP, Brazil
| | - Alba Regina Monteiro Souza-Brito
- Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas-UNICAMP, 13083-970, Campinas, SP, Brazil; Department of Structural and Functional Biology, Institute of Biology, State University of Campinas-UNICAMP, 13083-970, Campinas, SP, Brazil
| | - Matthias Hamburger
- Division of Pharmaceutical Biology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland
| | - Wagner Vilegas
- Institute of Biosciences, Coastal Campus of São Vicente, Universidade Estadual Paulista-UNESP, 11330-900, São Vicente, SP, Brazil.
| | - Emerson Ferreira Queiroz
- School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Centre Medical Universitaire-CMU, Rue Michel-Servet 1, CH-1211, Geneva 4, Switzerland.
| | - Jean-Luc Wolfender
- School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Centre Medical Universitaire-CMU, Rue Michel-Servet 1, CH-1211, Geneva 4, Switzerland
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Fahmy SR, Sayed DA. Toxicological perturbations of zinc oxide nanoparticles in the Coelatura aegyptiaca mussel. Toxicol Ind Health 2017; 33:564-575. [DOI: 10.1177/0748233716687927] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
More research is needed to understand the interactions of nanoparticles (NPs) with aquatic organisms and their mechanism of toxic action. Zinc oxide nanoparticles (ZnONPs) are the most used engineered metal oxide NPs in consumer products. The present study was designed to evaluate the cytotoxicity, genotoxicity and digestive gland (DG) as well as gill histopathology of the freshwater molluscan bivalve Coelatura aegyptiaca following exposure to ZnONPs (2, 10 and 50 mg/L) for 6 consecutive days. Exposure to ZnONPs (10 and 50 mg/L) induced a significant increase in malondialdehyde, superoxide dismutase and nitric oxide with a concomitant decrease in reduced glutathione, glutathione-S-transferase and catalase levels in the haemolymph, DG and gills of the treated mussels. Following exposure to ZnONPs (50 mg/L), the DG exhibited gradual changes in glandular activity showing hypertrophy and hyperplasia in the glandular cells and irregularity of lamellae and swelling of filaments in the gills. The present investigation revealed that oxidative stress induction, genotoxicity in the haemocytes and histological alterations in the DG and gills of C. aegyptiaca could be the main mechanisms involved in ZnONPs toxicity in aquatic organisms. Thereby, it is suggested that ZnONPs should be applied with more precautions in relevant industries, and occupational health surveillance should be necessarily considered.
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Affiliation(s)
- Sohair R Fahmy
- Zoology Department, Faculty of Science, Cairo University, Giza, Egypt
| | - Dawlat A Sayed
- Zoology Department, Faculty of Science, Cairo University, Giza, Egypt
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Gastroprotective activity of synthetic coumarins: Role of endogenous prostaglandins, nitric oxide, non-protein sulfhydryls and vanilloid receptors. Bioorg Med Chem Lett 2016; 26:5732-5735. [PMID: 27810240 DOI: 10.1016/j.bmcl.2016.10.056] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Revised: 10/18/2016] [Accepted: 10/19/2016] [Indexed: 02/06/2023]
Abstract
Natural or synthetic coumarins showed gastroprotective and antiulcer activity in animal models. In this study, we have synthetized twenty coumarins using classic methods to evaluate their gastroprotective effects on the ethanol/HCl-induced gastric lesion model in mice at 20mg/kg. Among the coumarins synthetized, compounds 6 and 10 showed the greatest gastroprotective activity being as active as lansoprazole at 20mg/kg and reducing gastric lesions by 75 and 76%, respectively. Then, in a second experiment, compounds 6 and 10 were re-evaluated in order to understand the possible mode of gastroprotective activity. Regarding coumarin 6, the protective effect was reduced by pre-treatment of the mice with N-ethylmaleimide and l-NAME suggesting that sulfhydryl compounds and endogenous nitric oxide are involved in its gastroprotective activity. While for coumarin 10 the effect was reduced by pre-treatment with indomethacin suggesting that prostaglandins are positively involved in its gastroprotective activity.
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Viana AFSC, da Silva FV, Fernandes HDB, Oliveira IS, Braga MA, Nunes PIG, Viana DDA, de Sousa DP, Rao VS, Oliveira RDCM, Almeida Santos F. Gastroprotective effect of (-)-myrtenol against ethanol-induced acute gastric lesions: possible mechanisms. ACTA ACUST UNITED AC 2016; 68:1085-92. [PMID: 27291136 DOI: 10.1111/jphp.12583] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2016] [Accepted: 05/14/2016] [Indexed: 12/25/2022]
Abstract
OBJECTIVES (-)-Myrtenol is a natural fragrance monoterpenoid structurally related to α-pinene found in diverse plant essential oils. This study was aimed to assess the anti-ulcerogenic potential of (-)-myrtenol against ethanol-induced gastric lesions and to elucidate the underlying mechanism(s). METHODS Gastroprotective activity of (-)-myrtenol was evaluated using the mouse model of ethanol-induced gastric damage. To elucidate the gastroprotective mechanism(s), the roles of GABA, prostaglandins, nitric oxide and KATP channels were assessed. Besides, the oxidative stress-related parameters and the mucus content in gastric tissues were analysed. KEY FINDINGS (-)-Myrtenol at oral doses of 25, 50 and 100 mg/kg significantly decreased the severity of ethanol-induced gastric lesions affording gastroprotection that was accompanied by a decrease in the activity of myeloperoxidase and malondialdehyde, an increase in GPx, SOD, and catalase activity in gastric tissues, and with well-maintained normal levels of nitrite/nitrate, gastric mucus and NP-SHs. Pretreatment with GABA-A receptor antagonist flumazenil, the COX inhibitor indomethacin, and NO synthesis inhibitor L-NAME but not with KATP channel blocker glibenclamide significantly blocked the (-)-myrtenol gastroprotection. CONCLUSION These results provide first-time evidence for the gastroprotective effect of (-)-myrtenol that could be related to GABAA -receptor activation and antioxidant activity.
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Affiliation(s)
- Ana Flávia Seraine Custódio Viana
- Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.,Medicinal Plants Research Center, Health Sciences Center, Federal University of Piauí, Teresina, Piauí, Brazil
| | - Francilene Vieira da Silva
- Medicinal Plants Research Center, Health Sciences Center, Federal University of Piauí, Teresina, Piauí, Brazil
| | - Hélio de Barros Fernandes
- Medicinal Plants Research Center, Health Sciences Center, Federal University of Piauí, Teresina, Piauí, Brazil
| | - Irisdalva Sousa Oliveira
- Medicinal Plants Research Center, Health Sciences Center, Federal University of Piauí, Teresina, Piauí, Brazil
| | - Milena Aguiar Braga
- Postgraduate Program in Biotechnology, Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Odontology and Nursing, Federal University of the Ceará, Fortaleza, Ceará, Brazil
| | - Paulo Iury Gomes Nunes
- Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - Daniel de Araújo Viana
- Laboratory of Pathology and Legal Medicine, Faculty of Veterinary Science, State University of Ceará, Fortaleza, Ceará, Brazil
| | | | - Vietla Satyanarayana Rao
- Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | | | - Flávia Almeida Santos
- Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
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Aliomrani M, Sepand MR, Mirzaei HR, Kazemi AR, Nekonam S, Sabzevari O. Effects of phloretin on oxidative and inflammatory reaction in rat model of cecal ligation and puncture induced sepsis. ACTA ACUST UNITED AC 2016; 24:15. [PMID: 27150961 PMCID: PMC4858854 DOI: 10.1186/s40199-016-0154-9] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2016] [Accepted: 04/27/2016] [Indexed: 01/21/2023]
Abstract
BACKGROUND Sepsis is a debilitating systemic disease and described as a severe and irregular systemic inflammatory reaction syndrome (SIRS) against infection. We employed CLP (Cecal Ligation and Puncture) model in rats to investigate anti-inflammatory and antioxidant effects of phloretin, as a natural antioxidant agent, and its protective effect on liver tissue damage caused by sepsis. METHODS Male Wistar albino rats were randomly divided into three groups: sham group, CLP induced sepsis group and phloretin treated CLP group. Sepsis was induced by CLP method. 50 mmol/kg Phloretin was administered intraperitoneally in two equal doses immediately after surgery. RESULTS It was observed that blood urea nitrogen (BUN) and tumor necrosis factor alpha (TNF-α) levels were dramatically increased in the CLP induced sepsis group (43.88 ± 1.905 mg/dl, 37.63 ± 1.92, respectively) when compared to the sham group. Moreover, tissue Glutathione (GSH) and liver nuclear factor ĸB (NF-ĸB p65) transcription factor values were higher in CLP induced sepsis group. This elevation was considerably reduced in the phloretin treated CLP group. No significant differences were observed in serum creatinine and creatinine phosphokinase levels. CONCLUSIONS The present study suggested that phloretin, as a natural protective agent, act against tissue damages introduced following the experimental sepsis induced model, likely caused by free oxygen radicals.
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Affiliation(s)
- Mehdi Aliomrani
- Toxicology and Poisoning Research Centre, Tehran University of Medical Sciences, Tehran, Iran.,Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, P. O. Box, 1417614411, Tehran, Iran
| | - Mohammad Reza Sepand
- Toxicology and Poisoning Research Centre, Tehran University of Medical Sciences, Tehran, Iran.,Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, P. O. Box, 1417614411, Tehran, Iran
| | - Hamid Reza Mirzaei
- Department of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Reza Kazemi
- Toxicology and Poisoning Research Centre, Tehran University of Medical Sciences, Tehran, Iran.,Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, P. O. Box, 1417614411, Tehran, Iran
| | - Saeid Nekonam
- Department of Anatomy, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Omid Sabzevari
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, P. O. Box, 1417614411, Tehran, Iran. .,Drug design and discovery Research Centre, Tehran University of Medical Sciences, Tehran, Iran.
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Ibrahim BM, Salama AA, Abdallah HM, El Awdan SA, Shaffie NM. Study of the Protective Effects of Flaxseed Oil on Ethanol Induced Gastric Mucosal Lesions in Non Ovariectomized and Ovariectomized Rats. INT J PHARMACOL 2016. [DOI: 10.3923/ijp.2016.329.339] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Carvalho NS, Silva MM, Silva RO, Nicolau LAD, Araújo TSL, Costa DS, Sousa NA, Souza LKM, Soares PMG, Medeiros JVR. Protective Effects of Simvastatin Against Alendronate-Induced Gastric Mucosal Injury in Rats. Dig Dis Sci 2016; 61:400-9. [PMID: 26403426 DOI: 10.1007/s10620-015-3890-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2015] [Accepted: 09/17/2015] [Indexed: 01/05/2023]
Abstract
BACKGROUND It has been reported that simvastatin, a statin commonly prescribed for its anti-inflammatory and antioxidant effects, has gastroprotective effects in indomethacin and ethanol-induced gastric ulcers. However, the effects of simvastatin on alendronate-induced gastric mucosal injury remain unexplored. AIM This study investigated the use of simvastatin for the treatment of alendronate-induced gastric ulcers in rats. METHODS Female rats were pretreated with vehicle or simvastatin (20 and 60 mg/kg p.o.). After 1 h, the rats received alendronate (50 mg/kg p.o.). Simvastatin was administered once daily for 7 days, and from the fourth day of simvastatin treatment, alendronate was administered once daily for 4 days. On the final day of treatment, 4 h after alendronate administration, animals were euthanized, their stomachs were removed, and gastric damage was measured. Samples of the stomach were fixed in 10 % formalin immediately after their removal for subsequent histopathological assessment. Unfixed samples were weighed, frozen at -80 °C until assayed for glutathione (GSH), malondialdehyde (MDA), and cytokine levels and myeloperoxidase (MPO) activity. A third group was used to measure mucus and gastric secretion. RESULTS Pretreatment with simvastatin prevented alendronate-induced macroscopic gastric damage and reduced the levels of MDA and GSH, TNF-α and IL-1β, MPO activity, and mucus levels, in the stomach. CONCLUSIONS This study demonstrates the protective effects of simvastatin against alendronate-induced gastric ulceration. Maintenance of mucosal integrity, inhibition of neutrophil activity, and reduced oxidative stress associated with decreased gastric acidity may explain the gastroprotective effects of simvastatin.
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Affiliation(s)
- Nathalia S Carvalho
- Post Graduation Program in Pharmacology, Medicinal Plant Research Center (NPPM), Federal University of Piauí, Teresina, PI, Brazil
| | - Mônica M Silva
- Post Graduation Program in Biotechnology, Biotechnology and Biodiversity Center Research (BIOTEC), Federal University of Piauí, Parnaíba, PI, Brazil
| | - Renan O Silva
- Laboratory of Pharmacology of Inflammation and Cancer (LAFICA), Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Lucas A D Nicolau
- Laboratory of Pharmacology of Inflammation and Cancer (LAFICA), Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Thiago S L Araújo
- Post Graduation Program in Biotechnology, Biotechnology and Biodiversity Center Research (BIOTEC), Federal University of Piauí, Parnaíba, PI, Brazil
| | - Douglas S Costa
- Post Graduation Program in Pharmacology, Medicinal Plant Research Center (NPPM), Federal University of Piauí, Teresina, PI, Brazil
| | - Nayara A Sousa
- Post Graduation Program in Biotechnology, Biotechnology and Biodiversity Center Research (BIOTEC), Federal University of Piauí, Parnaíba, PI, Brazil
| | - Luan K M Souza
- Post Graduation Program in Biotechnology, Biotechnology and Biodiversity Center Research (BIOTEC), Federal University of Piauí, Parnaíba, PI, Brazil
| | - Pedro M G Soares
- Laboratory of Pharmacology of Inflammation and Cancer (LAFICA), Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Jand Venes R Medeiros
- Post Graduation Program in Pharmacology, Medicinal Plant Research Center (NPPM), Federal University of Piauí, Teresina, PI, Brazil. .,Post Graduation Program in Biotechnology, Biotechnology and Biodiversity Center Research (BIOTEC), Federal University of Piauí, Parnaíba, PI, Brazil. .,BIOTEC/LAFFEX/UFPI, Av. São Sebastião, no. 2819, Parnaíba, PI, CEP 64202-020, Brazil.
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Maurya PK, Kumar P, Nagotu S, Chand S, Chandra P. Multi-target detection of oxidative stress biomarkers in quercetin and myricetin treated human red blood cells. RSC Adv 2016. [DOI: 10.1039/c6ra05121a] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
Quercetin and myricetin help against oxidative stress in human red blood cells during aging, thereby has tremendous scope in medical diagnostics and therapeutics.
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Affiliation(s)
- Pawan Kumar Maurya
- Amity Institute of Biotechnology
- Amity University Uttar Pradesh
- Noida
- India
- Interdisciplinary Laboratory for Clinical Neuroscience (LiNC)
| | - Prabhanshu Kumar
- Amity Institute of Biotechnology
- Amity University Uttar Pradesh
- Noida
- India
| | - Shirisha Nagotu
- Department of Biosciences and Bioengineering
- Indian Institute of Technology-Guwahati
- Guwahati-781 039
- India
| | - Subhash Chand
- Department of Biochemical Engineering & Biotechnology
- Indian Institute of Technology
- Delhi
- India
| | - Pranjal Chandra
- Department of Biosciences and Bioengineering
- Indian Institute of Technology-Guwahati
- Guwahati-781 039
- India
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15
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Velázquez-Moyado JA, Martínez-González A, Linares E, Bye R, Mata R, Navarrete A. Gastroprotective effect of diligustilide isolated from roots of Ligusticum porteri coulter & rose (Apiaceae) on ethanol-induced lesions in rats. JOURNAL OF ETHNOPHARMACOLOGY 2015; 174:403-409. [PMID: 26320689 DOI: 10.1016/j.jep.2015.08.030] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Revised: 07/03/2015] [Accepted: 08/22/2015] [Indexed: 06/04/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The rhizome of Ligusticum porteri Coulter& Rose (LP) has been traditionally used by the ethnic group Raramuri in the North of México for treatment of diabetes, tuberculosis, stomachaches, diarrhea and ritual healing ceremonies. It is use as antiulcer remedy has been extended to all Mexico. AIM OF THE STUDY To evaluate the gastroprotective activity of LP organic extracts and the major natural product diligustilide (DLG),using as experimental model the inhibition of the ethanol-induced lesions in rats. MATERIALS AND METHODS Gastric ulcers were induced by intragastric instillation of absolute ethanol (1 mL). We tested the gastroprotective activity of the organic extracts of LP and the pure compound DLG. The ulcer index (UI) was determined to measure the activity. In order to elucidate the action mechanism of DLG the animals were treated with L-NAME, N-ethylmalemide, Forskolin, 2',5'-dideoxyadenosine, Indomethacin, Glibenclameide, Diazoxide, NaHS and DL-Propargylglycine. The pylorus-ligated rat model was used to measure gastric secretion. RESULTS The oral administration of organic extracts of Ligusticum porteri showed gastroprotective effect at 30 mg/Kg on ethanol induced gastric lesions; hexane and dichloromethane extracts were the most active. DLG was the major compound in the hexane extract. This compound at 10 mg/kg prevented significantly the gastric injuries induced by ethanol. The alkylation of endogenous non-protein-SH groups with N-ethylmaleimide abolished the gastroprotective effect of DLG and blocking the formation of endogenous prostaglandins by the pretreatment with indomethacin attenuated the gastroprotective effect of DLG. CONCLUSION The gastroprotective activity demonstrated in this study tends to support the ethnomedical use of Ligusticum porteri roots. DLG, isolated as major compound of this medicinal plant has a clear gastroprotective effect on the ethanol-induced gastric lesions. The results suggest that the antiulcer activity of DLG depends on the participation of the endogenous non-protein -SH groups and prostaglandins.
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Affiliation(s)
- Josué A Velázquez-Moyado
- Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán 04510, México D.F., México
| | - Alejandro Martínez-González
- Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán 04510, México D.F., México
| | - Edelmira Linares
- Instituto de Biología, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán 04510, México D.F., México
| | - Robert Bye
- Instituto de Biología, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán 04510, México D.F., México
| | - Rachel Mata
- Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán 04510, México D.F., México
| | - Andrés Navarrete
- Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán 04510, México D.F., México.
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16
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Fathollahi A, Daneshgari F, Hanna-Mitchell AT. Melatonin and Its Role in Lower Urinary Tract Function: An Article Review. Curr Urol 2015; 8:113-8. [PMID: 26889129 DOI: 10.1159/000365701] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2015] [Accepted: 02/20/2015] [Indexed: 01/19/2023] Open
Abstract
This article reviewed the results of studies done on animals that assessed effects of melatonin on bladder function. Melatonin does not change strip relaxation on its own. However, pre-treatment with melatonin decreases contractile responses induced by phenylephrine, acetylcholine, bethanechol and KCl in a dose-dependent manner. The contractile responses induced by the direct calcium channel openers are significantly decreased by melatonin pre-treatment. It also binds to Ca(2+)-activated calmodulin, and prevents it from activating myosin light-chain kinase. It may have direct effects on ion channels which are responsible for regulating bladder contraction. Its other mode of action on bladder occurs via the brain GABAA receptor. Melatonin is an antioxidant. In bladder, treatment with melatonin prevents elevations in malondialdehyde levels, reverses changes in glutathione levels, and decreases myeloperoxidase levels compared with oxidative injury. It can normalize age induced bladder dysfunction through its antioxidant effects, inhibiting smooth muscle contractility directly and restoring impaired contractility via normalization of Ca(2+) handling and sensitizations pathways. It attenuates the severity of cystitis and inflammation. Mast cell proliferation and activation are increased in cystitis, but decrease by melatonin treatment. Also, there is a decrease in expression levels of pro-inflammatory cytokines after melatonin treatment.
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Affiliation(s)
- Ali Fathollahi
- Urology Institute, Case Western Reserve University, Cleveland, OH., USA
| | - Firouz Daneshgari
- Urology Institute, Case Western Reserve University, Cleveland, OH., USA
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17
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Périco LL, Heredia-Vieira SC, Beserra FP, de Cássia Dos Santos R, Weiss MB, Resende FA, Dos Santos Ramos MA, Bonifácio BV, Bauab TM, Varanda EA, de Gobbi JIF, da Rocha LRM, Vilegas W, Hiruma-Lima CA. Does the gastroprotective action of a medicinal plant ensure healing effects? An integrative study of the biological effects of Serjania marginata Casar. (Sapindaceae) in rats. JOURNAL OF ETHNOPHARMACOLOGY 2015; 172:312-324. [PMID: 26099637 DOI: 10.1016/j.jep.2015.06.025] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/06/2015] [Revised: 06/03/2015] [Accepted: 06/14/2015] [Indexed: 06/04/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Serjania marginata (Sapindaceae), a medicinal plant commonly found in the Brazilian Cerrado, Paraguay, Bolivia and Argentina, is also known as "cipó-uva" or "cipó-timbó". Ethnopharmacological studies indicate that the leaves from this medicinal plant are used in folk medicine to treat gastric pain. The overall objective of this study was to evaluate the gastroprotective and healing effect of the hydroalcoholic extract obtained from S. marginata (HESM) leaves using rodent experimental models. As part of the integrative study of this medicinal plant, we also evaluated the acute toxicity, antimicrobial, antidiarrheal, (anti)mutagenic, and hemodynamic effects. MATERIAL AND METHODS We performed a pharmacological study to test the acute toxicity and antimutagenic effect (Ames assay) of the HESM. The HESM was tested against different necrosis-promoting agents and experimental manipulations, such as absolute ethanol, cysteamine, pyloric ligature, and ischemia-reperfusion (I/R) injury. The gastroprotective effect of the HESM was assessed by analyzing the gastric juice (volume, pH, total acidity) and the mucus in the gastric mucosa from rats. We assessed the levels of NO, sulfhydryl compounds, PGE2, vanilloid receptor, glutathione (GSH), and malondialdehyde (MDA), as well as the myeloperoxidase (MPO) activity. The gastric healing effects of the HESM were evaluated during 7 or 14 days of treatment. The intestinal motility, antidiarrheal action, and antibacterial effects (microdilution methods) of the HESM were also evaluated. RESULTS The phytochemical analysis of the HESM revealed the presence of saponins, flavonoid glycosides, and tannins. The extract exhibited no sign of acute toxicity or mutagenic effect in vitro. In contrast, this extract exhibited a protective effect against the mutagenic action of direct- and indirect-acting mutagens. Only the oral administration of HESM (250mg/kg) significantly decreased the severity of gastric damage induced by ethanol (60.13%) and I/R (58.31%). The HESM exerts its gastroprotective effects by decreasing the MPO and MDA activities in the gastric tissue and by increasing the amount of adherent mucus covering the gastric mucosa. In vitro, the extract also displayed evident antimicrobial effects against Helicobacter pylori. However, the preventive effect of the HESM was not accompanied by an ulcer-healing effect. The treatment with HESM (14 days) significantly increased gastric lesions in 99% of the tested animals compared with the control group. This result represents a highly relevant piece of evidence that should resonate as an alert against the chronic use of this medicinal plant as an antiulcer in folk medicine. CONCLUSIONS Despite the anti-H. pylori and gastroprotective actions of S. marginata in experimental models, the gastric injuries aggravation induced after chronic treatment with the HESM argues against the use of this plant species in folk medicine.
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Affiliation(s)
- Larissa Lucena Périco
- Univ. Estadual Paulista-UNESP, Departamento de Fisiologia, Instituto de Biociências, CEP 18618-970, Botucatu, SP, Brazil
| | | | - Fernando Pereira Beserra
- Univ. Estadual Paulista-UNESP, Departamento de Fisiologia, Instituto de Biociências, CEP 18618-970, Botucatu, SP, Brazil
| | - Raquel de Cássia Dos Santos
- Universidade São Francisco, Faculdade de Ciências Médicas, Unidade Integrada de Farmacologia e Gastroenterologia, CEP 12916-900, Bragança Paulista, SP, Brazil
| | - Marcio Barczyszyn Weiss
- Univ. Estadual Paulista-UNESP, Faculdade de Ciências Farmacêuticas, CEP 14800-902, Araraquara, SP, Brazil
| | - Flavia Aparecida Resende
- Univ. Estadual Paulista-UNESP, Faculdade de Ciências Farmacêuticas, CEP 14800-902, Araraquara, SP, Brazil
| | | | - Bruna Vidal Bonifácio
- Univ. Estadual Paulista-UNESP, Faculdade de Ciências Farmacêuticas, CEP 14800-902, Araraquara, SP, Brazil
| | - Taís Maria Bauab
- Univ. Estadual Paulista-UNESP, Faculdade de Ciências Farmacêuticas, CEP 14800-902, Araraquara, SP, Brazil
| | - Eliana Aparecida Varanda
- Univ. Estadual Paulista-UNESP, Faculdade de Ciências Farmacêuticas, CEP 14800-902, Araraquara, SP, Brazil
| | | | - Lúcia Regina Machado da Rocha
- Univ. Estadual Paulista-UNESP, Departamento de Fisiologia, Instituto de Biociências, CEP 18618-970, Botucatu, SP, Brazil
| | - Wagner Vilegas
- Univ. Estadual Paulista-UNESP, Campus Experimental do Litoral Paulista, CEP 11330-900, São Vicente, SP, Brazil
| | - Clélia Akiko Hiruma-Lima
- Univ. Estadual Paulista-UNESP, Departamento de Fisiologia, Instituto de Biociências, CEP 18618-970, Botucatu, SP, Brazil.
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Parra T, Benites J, Ruiz LM, Sepulveda B, Simirgiotis M, Areche C. Gastroprotective activity of ent-beyerene derivatives in mice: Effects on gastric secretion, endogenous prostaglandins and non-protein sulfhydryls. Bioorg Med Chem Lett 2015; 25:2813-7. [DOI: 10.1016/j.bmcl.2015.04.095] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2015] [Revised: 04/23/2015] [Accepted: 04/30/2015] [Indexed: 01/08/2023]
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Arab HH, Salama SA, Omar HA, Arafa ESA, Maghrabi IA. Diosmin protects against ethanol-induced gastric injury in rats: novel anti-ulcer actions. PLoS One 2015; 10:e0122417. [PMID: 25821971 PMCID: PMC4378914 DOI: 10.1371/journal.pone.0122417] [Citation(s) in RCA: 178] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2014] [Accepted: 02/20/2015] [Indexed: 01/26/2023] Open
Abstract
Alcohol consumption has been commonly associated with gastric mucosal lesions including gastric ulcer. Diosmin (DIO) is a natural citrus flavone with remarkable antioxidant and anti-inflammatory features that underlay its protection against cardiac, hepatic and renal injuries. However, its impact on gastric ulcer has not yet been elucidated. Thus, the current study aimed to investigate the potential protective effects of DIO against ethanol-induced gastric injury in rats. Pretreatment with DIO (100 mg/kg p.o.) attenuated the severity of ethanol gastric mucosal damage as evidenced by lowering of ulcer index (UI) scores, area of gastric lesions, histopathologic aberrations and leukocyte invasion. These actions were analogous to those exerted by the reference antiulcer sucralfate. DIO suppressed gastric inflammation by curbing of myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) levels along with nuclear factor kappa B (NF-κB) p65 expression. It also augmented the anti-inflammatory interleukin-10 (IL-10) levels. Meanwhile, DIO halted gastric oxidative stress via inhibition of lipid peroxides with concomitant enhancement of glutathione (GSH), glutathione peroxidase (GPx) and the total antioxidant capacity (TAC). With respect to gastric mucosal apoptosis, DIO suppressed caspase-3 activity and cytochrome C (Cyt C) with enhancement of the anti-apoptotic B cell lymphoma-2 (Bcl-2) in favor of cell survival. These favorable actions were associated with upregulation of the gastric cytoprotective prostaglandin E2 (PGE2) and nitric oxide (NO). Together, these findings accentuate the gastroprotective actions of DIO in ethanol gastric injury which were mediated via concerted multi-pronged actions, including suppression of gastric inflammation, oxidative stress and apoptosis besides boosting of the antioxidant and the cytoprotective defenses.
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Affiliation(s)
- Hany H. Arab
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt
- Biochemistry Division and GTMR Unit, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Taif University, Taif, 21974, Saudi Arabia
- * E-mail:
| | - Samir A. Salama
- Biochemistry Division and GTMR Unit, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Taif University, Taif, 21974, Saudi Arabia
- Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, 11751, Egypt
| | - Hany A. Omar
- Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt
- Sharjah Institute for Medical Research, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab of Emirates
| | - El-Shaimaa A. Arafa
- Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt
| | - Ibrahim A. Maghrabi
- Department of Clinical Pharmacy, Faculty of Pharmacy, Taif University, Taif, 21974, Saudi Arabia
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20
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Fahmy SR. Anti-fibrotic effect of Holothuria arenicola extract against bile duct ligation in rats. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2015; 15:14. [PMID: 25652675 PMCID: PMC4328034 DOI: 10.1186/s12906-015-0533-7] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/21/2014] [Accepted: 01/19/2015] [Indexed: 02/08/2023]
Abstract
BACKGROUND Holothuria arenicola is the most important and abundant sea cucumber species in the Mediterranean Sea on the Egyptian coast. The present study aims to assess the anti-oxidative and anticholestatic effects of the sea cucumber Holothuria arenicola extract (HaE) in a model of bile duct ligation in male albino rats. METHODS Fifty four male Wistar albino rats were assigned into two main groups, the Sham-operated control and bile duct ligated (BDL) group. After 14 days of surgery, the animals of the group I (Sham control) received distilled water only for 7, 14 and 28 days. Second group (BDL group) was divided into 2 subgroups, animals of these subgroups treated for 7, 14 and 28 consecutive days as follow: subgroup I (BDL), rats of this subgroup administered distilled water orally. Subgroup II (HaE), animals of this subgroup treated orally with HaE (200 mg/kg body weight). RESULTS The HaE revealed significant antifibrotic effect as evident by decreasing the levels of total conjugated and unconjugated bilirubin and the activities of serum aminotransferases (ASAT and ALAT) and alkaline phosphatase (ALP) as well as malondialdehyde (MDA) level, and increasing the serum albumin, glutathione reduced (GSH) levels. Treatment with HaE normalized the antioxidant enzyme, glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) activities activities. CONCLUSION The present prospective study correlated the antifibrotic effect of HaE to its direct antioxidant effect that can be related to its contents of phenolic compounds specially chlorogenic acid, pyrogallol, rutin and coumaric acid.
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Affiliation(s)
- Sohair R Fahmy
- Department of Zoology, Faculty of Science, Cairo University, 12613, Giza, Egypt.
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21
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Abstract
Although Andre Robert's historic article on "gastric cytoprotection" in 1979 introduced this new name and concept, gastroprotective drugs (e.g. sofalcone, sucralfate), which prevent and/or accelerate healing of gastric ulcers without inhibiting acid secretion, were known in Japan before or around that time. But since Robert's studies were solely focused on prostaglandins (PG), they became the center of gastrointestinal research for more than 30 years. As endogenous products, PG were implicated in mediating the gastroprotective effect of other drugs such as sofalcone and sucralfate, despite that the cyclooxygenase inhibitor indomethacin diminished but never abolished gastroprotection by other drugs. Another group of endogenous substances, that is, sulfhydryls (SH), investigated in parallel with PG, also seem to play a mechanistic role in gastroprotection, especially since SH alkylators like N-ethylmaleimide counteract virtually any form of gastroprotection. In Robert's terms of "prevention of chemically induced acute mucosal lesions," so far no single mechanism could explain the beneficial effects of diverse protective agents, but I argue that these two endogenous substances (i.e. PG, SH), in addition to histamine, are the main mechanistic mediators of acute gastroprotection: PG and histamine, because as mediators of acute inflammation, they increase vascular permeability (VP), and SH scavenge free radicals. This is contrary to the search for a single mechanism of action, long focused on enhanced secretion of mucus and/or bicarbonate that may contribute but cannot explain all forms of gastroprotection. Nevertheless, based on research work of the last 30 years, in part from our lab, a new mechanistic explanation of gastroprotection may be formulated: it's a complex but orderly and evolution-based physiologic response of the gastric mucosa under pathologic conditions. Namely, one of the first physiologic defense responses of any organ is inflammation that starts with rapid vascular changes (e.g. increased VP and blood flow), followed by cellular events (e.g. infiltration by acute and chronic inflammatory cells). Thus, PG and histamine, by increasing VP create a perivascular edema that dilutes and delays toxic agents reaching the subepithelial capillaries. Otherwise, damaging chemicals may induce severe early vascular injury resulting in blood flow stasis, hypoxia, and necrosis of surrounding epithelial and mesenchymal cells. In this complex response, increased mucus and/or bicarbonate secretion seem to cause luminal dilution of gastrotoxic chemicals that is further reinforced by a perivascular, histodilutional component. This mechanistic explanation would encompass the protective actions of diverse agents as PG, small doses of histamine, motility stimulants, and dilute irritants (i.e. "adaptive cytoprotection"). Thus, although markedly increased VP is pathologic, slight increase in VP seems to be protective, that is, a key element in the complex pathophysiologic response during acute gastroprotection. Over the years, "gastroprotection" was also applied to accelerated healing of chronic gastroduodenal ulcers without reduction of acid secretion. The likely main mechanism here is the binding of angiogenic growth factors (e.g. basic fibroblast growth factor, vascular endothelial growth factor) to the heparin-like structures of sucralfate and sofalcone. Thus, despite intensive research of the last 30 years, gastroprotection is incompletely understood, and we are still far away from effectively treating Helicobacter pylori-negative ulcers and preventing nonsteroidal anti-inflammatory drugs-caused erosions and ulcers in the upper and lower gastrointestinal tract; hence "gastric cytoprotection" research is still relevant.
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Affiliation(s)
- Sandor Szabo
- Departments of Pathology and Pharmacology, University of California-Irvine and VA Medical Center, Long Beach, California, USA
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22
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Song DU, Jang MS, Kim HW, Yoon HJ, Chay KO, Joo YE, Jung YD, Yang SY, Ahn BW. Gastroprotective Effects of Glutinous Rice Extract against Ethanol-, Indomethacin-, and Stress-induced Ulcers in Rats. Chonnam Med J 2014; 50:6-14. [PMID: 24855601 PMCID: PMC4022797 DOI: 10.4068/cmj.2014.50.1.6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2013] [Revised: 01/27/2014] [Accepted: 01/28/2014] [Indexed: 12/12/2022] Open
Abstract
This study was designed to evaluate the efficacy of an orally administered aqueous extract of glutinous rice (GRE) to protect against acute gastric mucosal lesions induced by ethanol, indomethacin, and water immersion restraint stress in rats and to characterize the active substances responsible for the protection. GRE was shown to dose-dependently prevent the gastric lesions induced by the above ulcerogenic treatments at doses of 30 to 300 mg/kg. GRE treatment increased the gastric mucin content and partially blocked the ethanol-induced depletion of the gastric mucus layer. Also, it increased the nonprotein sulfhydryl concentration in the gastric mucosa. The gastroprotective action of GRE was markedly enhanced by co-treatment with 4-8 mg/kg tea extracts. The activity of GRE was completely lost by heat treatment at 80℃ for 3 min or treatment with 0.01% pepsin at 37℃ for 1 h. Protein extraction studies indicated that prolamins are involved in the gastroprotective activity of GRE. Our results suggest that glutinous rice proteins are useful for the prevention and treatment of gastritis and peptic ulcer.
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Affiliation(s)
- Dong Up Song
- Chonnam University Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju, Korea
| | - Mi Sun Jang
- Chonnam University Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju, Korea
| | - Hyun Woo Kim
- Chonnam University Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju, Korea
| | - Hyun Joong Yoon
- Department of Biochemistry, Chonnam National University Medical School, Gwangju, Korea
| | - Kee Oh Chay
- Department of Biochemistry, Chonnam National University Medical School, Gwangju, Korea
| | - Young Eun Joo
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Young Do Jung
- Department of Biochemistry, Chonnam National University Medical School, Gwangju, Korea
| | - Sung Yeul Yang
- Department of Biochemistry, Chonnam National University Medical School, Gwangju, Korea
| | - Bong Whan Ahn
- Department of Biochemistry, Chonnam National University Medical School, Gwangju, Korea
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Geraniol—a flavoring agent with multifunctional effects in protecting the gastric and duodenal mucosa. Naunyn Schmiedebergs Arch Pharmacol 2013; 387:355-65. [DOI: 10.1007/s00210-013-0947-z] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2013] [Accepted: 12/02/2013] [Indexed: 10/25/2022]
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Ineu RP, Oliveira CS, Oliveira VA, Moraes-Silva L, da Luz SCA, Pereira ME. Antioxidant effect of zinc chloride against ethanol-induced gastrointestinal lesions in rats. Food Chem Toxicol 2013; 58:522-9. [DOI: 10.1016/j.fct.2013.05.022] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2013] [Revised: 04/30/2013] [Accepted: 05/02/2013] [Indexed: 01/22/2023]
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25
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Nicolau L, Silva R, Damasceno S, Carvalho N, Costa N, Aragão K, Barbosa A, Soares P, Souza M, Medeiros J. The hydrogen sulfide donor, Lawesson's reagent, prevents alendronate-induced gastric damage in rats. Braz J Med Biol Res 2013; 46:708-14. [PMID: 23969974 PMCID: PMC3854416 DOI: 10.1590/1414-431x20133030] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2013] [Accepted: 06/21/2013] [Indexed: 11/21/2022] Open
Abstract
Our objective was to investigate the protective effect of Lawesson's reagent, an H2S donor, against alendronate (ALD)-induced gastric damage in rats. Rats were pretreated with saline or Lawesson's reagent (3, 9, or 27 µmol/kg, po) once daily for 4 days. After 30 min, gastric damage was induced by ALD (30 mg/kg) administration by gavage. On the last day of treatment, the animals were killed 4 h after ALD administration. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-1β], and myeloperoxidase (MPO). Other groups were pretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5 mg/kg, ip)+diazoxide (3 mg/kg, ip). After 1 h, 27 µmol/kg Lawesson's reagent was administered. After 30 min, 30 mg/kg ALD was administered. ALD caused gastric damage (63.35 ± 9.8 mm(2)); increased levels of TNF-α, IL-1β, and MDA (2311 ± 302.3 pg/mL, 901.9 ± 106.2 pg/mL, 121.1 ± 4.3 nmol/g, respectively); increased MPO activity (26.1 ± 3.8 U/mg); and reduced GSH levels (180.3 ± 21.9 µg/g). ALD also increased cystathionine-γ-lyase immunoreactivity in the gastric mucosa. Pretreatment with Lawesson's reagent (27 µmol/kg) attenuated ALD-mediated gastric damage (15.77 ± 5.3 mm(2)); reduced TNF-α, IL-1β, and MDA formation (1502 ± 150.2 pg/mL, 632.3 ± 43.4 pg/mL, 78.4 ± 7.6 nmol/g, respectively); lowered MPO activity (11.7 ± 2.8 U/mg); and increased the level of GSH in the gastric tissue (397.9 ± 40.2 µg/g). Glibenclamide alone reversed the gastric protective effect of Lawesson's reagent. However, glibenclamide plus diazoxide did not alter the effects of Lawesson's reagent. Our results suggest that Lawesson's reagent plays a protective role against ALD-induced gastric damage through mechanisms that depend at least in part on activation of ATP-sensitive potassium (KATP) channels.
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Affiliation(s)
- L.A.D. Nicolau
- Núcleo de Pesquisa em Produtos Naturais, Departamento de
Farmacologia, Universidade Federal do Piauí, Teresina, PI, Brasil
| | - R.O. Silva
- Laboratório de Fisiofarmacologia Experimental, Centro de Pesquisa em
Biodiversidade e Biotecnologia, Universidade Federal do Piauí, Parnaíba, PI, Brasil
| | - S.R.B. Damasceno
- Laboratório de Fisiofarmacologia Experimental, Centro de Pesquisa em
Biodiversidade e Biotecnologia, Universidade Federal do Piauí, Parnaíba, PI, Brasil
| | - N.S. Carvalho
- Laboratório de Fisiofarmacologia Experimental, Centro de Pesquisa em
Biodiversidade e Biotecnologia, Universidade Federal do Piauí, Parnaíba, PI, Brasil
| | - N.R.D. Costa
- Laboratório de Fisiofarmacologia Experimental, Centro de Pesquisa em
Biodiversidade e Biotecnologia, Universidade Federal do Piauí, Parnaíba, PI, Brasil
| | - K.S. Aragão
- Laboratório de Farmacologia da Inflamação e do Câncer, Departamento
de Farmacologia, Universidade Federal do Ceará, Fortaleza, CE, Brasil
| | - A.L.R. Barbosa
- Núcleo de Pesquisa em Produtos Naturais, Departamento de
Farmacologia, Universidade Federal do Piauí, Teresina, PI, Brasil
- Laboratório de Fisiofarmacologia Experimental, Centro de Pesquisa em
Biodiversidade e Biotecnologia, Universidade Federal do Piauí, Parnaíba, PI, Brasil
| | - P.M.G. Soares
- Laboratório de Farmacologia da Inflamação e do Câncer, Departamento
de Farmacologia, Universidade Federal do Ceará, Fortaleza, CE, Brasil
| | - M.H.L.P. Souza
- Laboratório de Farmacologia da Inflamação e do Câncer, Departamento
de Farmacologia, Universidade Federal do Ceará, Fortaleza, CE, Brasil
| | - J.V.R. Medeiros
- Núcleo de Pesquisa em Produtos Naturais, Departamento de
Farmacologia, Universidade Federal do Piauí, Teresina, PI, Brasil
- Laboratório de Fisiofarmacologia Experimental, Centro de Pesquisa em
Biodiversidade e Biotecnologia, Universidade Federal do Piauí, Parnaíba, PI, Brasil
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Affiliation(s)
- Eddie Weitzberg
- Department of Physiology and Pharmacology, 1Section for Anesthesiology and Intensive Care,
| | - Jon O. Lundberg
- Division of Pharmacology, Karolinska Institutet, S-171 77, Stockholm, Sweden; ,
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Effect of protein malnutrition on the metabolism and toxicity of cisplatin, 5-fluorouracil and mitomycin C in rat stomach. Food Chem Toxicol 2013; 56:467-82. [DOI: 10.1016/j.fct.2013.02.042] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2012] [Revised: 12/25/2012] [Accepted: 02/18/2013] [Indexed: 01/06/2023]
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Rodrigues e Silva AA, Marques Bezerra M, Vasconcelos Chaves H, de Paulo Teixeira Pinto V, de Souza Franco E, Magalhães Vieira A, Barbosa Araújo E, Cunha Rios L, Resende Leite AC, de Sousa Maia MB. Protective effect of Chresta martii extract on ethanol-induced gastropathy depends on alpha-2 adrenoceptors pathways but not on nitric oxide, prostaglandins or opioids. JOURNAL OF ETHNOPHARMACOLOGY 2012; 142:206-212. [PMID: 22564358 DOI: 10.1016/j.jep.2012.04.042] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/2011] [Revised: 04/09/2012] [Accepted: 04/22/2012] [Indexed: 05/31/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Species of Chresta genus- are recognized by the population of northeastern Brazil as traditional herbs used to treat gastric diseases and other disorders. AIM OF THE STUDY This work aimed to find out the action mechanism of Chresta martii hydro alcoholic extract gastro protective effect in the model of ethanol-induced gastropathy. MATERIAL AND METHODS Gastropathy was assessed by percentual damaged area determination in photographs of mice opened stomachs. Fasted mice treated with ethanol 99.9% (0.2 ml/animal, p.o.) were pre-treated with Chresta martii hydro alcoholic extract (HAE) (50, 100 or 200 mg/kg, p.o.), ranitidine (80 mg/kg, p.o.) or saline (5 ml/kg; p.o.) in different experimental sets, in which pharmacological tools (naloxone, indomethacin, N(ω)-Nitro-L-arginine methyl ester hydrochloride (L-NAME) or yohimbine) were added in order to clarify a possible action mechanism. Animals were sacrificed 30 min after ethanol challenge to stomach analysis. Determination of non-protein sulfhydryl groups and tissue hemoglobin, besides histological assessment (H&E) were taken to fully characterize the HAE gastro protective effect. RESULTS HAE (100 and 200 mg/kg) was able to protect mucosa against ethanol gastropathy in presence of three (naloxone, indomethacin and L-NAME) of four antagonist/inhibitor tools. The HAE effect was reversed only by yohimbine, showing the alpha-2 adrenoceptors participation on gastro protective effect of this extract. HAE histological characteristics, NP-SH and Hb were compatible with the protective effects. CONCLUSIONS HAE possesses gastroprotective effects in an ethanol-induced gastropathy model in mice, corroborating the traditional use of this family of plants to treat gastric disorders. This activity is mediated by alpha-2 adrenoceptors activation, but not by nitric oxide release, opioid receptor activation or prostaglandin synthesis. HAE also has antioxidant activity that is thought to either play a role in this biological activity or to be a byproduct of alpha-2 adrenergic complex activation.
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Affiliation(s)
- Antonio Alfredo Rodrigues e Silva
- Laboratory of Pharmacology of Sobral-LaFS, Federal University of Ceará. Av. Comandante Maurocélio Rocha Pontes 100, Derby, CEP 62.042-280, Sobral, Ceará, Brazil.
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Silva AAR, Bezerra MM, Chaves HV, Pereira KMA, Aguiar JA, Pinto VPT, Abbet C, Simões-Pires CA, Franco ES, Henriques AT, Hostettmann K, Maia MBS. Protective effect of Chresta martii extract against indomethacin-induced gastric lesions in mice. J Nat Med 2012; 67:143-51. [PMID: 22450730 DOI: 10.1007/s11418-012-0663-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2012] [Accepted: 03/12/2012] [Indexed: 10/28/2022]
Abstract
Chresta martii (Asteraceae) is a plant found in the Xingó region (semi-arid area) in Northeastearn Brazil, and is recognized by the local population as a traditional herb used to treat gastric diseases. This is the first report of the chemical composition, acute toxicity, and gastroprotective effect in mice of the hydroalcoholic extract (HAE) from the aerial parts (leaves and flowers) of Chresta martii. Animals received HAE doses from 10 to 2000 mg/kg, i.p. or 50 to 3000 mg/kg, p.o.) and were observed over 48 h for toxicity signs and mortality; sub-chronic toxicity was evaluated through 14 days treatment with once-daily HAE doses (400 mg/kg, p.o.). The gastroprotective effect of HAE was demonstrated on the indomethacin-induced gastric ulcer model after the administration of extracts. Data comparison of ulcer index averages between saline and HAE (100 or 400 mg/kg, p.o.) groups showed significant (P < 0.01) inhibition (71.73 and 76.72 %, respectively) of indomethacin-induced gastric lesions. Histological analyses showed significant (P < 0.05) inhibition of leukocyte migration in HAE-treated groups. A fingerprint of the HAE obtained by HPLC/UV/MS analysis showed major peaks characteristic of sesquiterpene lactones. Compound 1 was isolated and elucidated as a new natural product. Its capacity to prevent leukocyte chemotaxis was demonstrated in vitro, corroborating the pharmacological effects observed for C. martii HAE.
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Affiliation(s)
- A A R Silva
- Federal University of Ceará Brazil, Avenida Comandante Maurocélio Rocha Pontes, Sobral, Brazil.
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Deniz M, Şener G, Ercan F, Yeğen BÇ. Garlic extract ameliorates renal and cardiopulmonary injury in the rats with chronic renal failure. Ren Fail 2011; 33:718-25. [PMID: 21787163 DOI: 10.3109/0886022x.2011.589952] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Chronic renal failure (CRF) is associated with oxidative stress that promotes production of reactive oxygen species and cytokine release. We aimed to investigate the possible protective and antioxidant effects of aqueous garlic extract (AGE) in a rat model of CRF. Male Sprague-Dawley rats were randomly assigned as either CRF group with 5/6 reduction in the renal mass or sham-operated control group. CRF group received either saline or AGE (250 mg/kg/day/1 mL) orally for 3 weeks. At the end of the 3 weeks, rats were decapitated and trunk blood was collected. Creatinine, blood urea nitrogen (BUN) and lactate dehydrogenase (LDH) activity, and TNF-α and IL-1β levels were measured in the serum samples, while malondialdehyde (MDA), glutathione (GSH) levels, and myeloperoxidase (MPO) activity were determined in the kidney, lung, and heart samples. CRF caused significant decreases in tissue GSH, which were accompanied with significant increases in MDA levels and MPO activities, while the circulating levels of the LDH activity, creatinine, BUN, TNF-α, and IL-1β were elevated. AGE treatment alleviated CRF-induced oxidative changes in the injured tissues, while CRF-induced elevations in the blood levels of the pro-inflammatory cytokines and LDH were reduced. In conclusion, CRF-induced oxidative tissue injury occurs via the activation of pro-inflammatory mediators and by neutrophil infiltration into tissues and that the protective effects of garlic on CRF-induced injury can be attributed to its ability to inhibit neutrophil infiltration and pro-inflammatory mediators. These findings suggest that garlic, as a supplementary to diet, may have a potential therapeutic use in delimitating the systemic oxidant effects of CRF on remote organs.
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Affiliation(s)
- Mustafa Deniz
- Department of Physiology, School of Medicine, Çanakkale Onsekiz Mart University, Çanakkale, Turkey
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Tavares T, Monteiro K, Possenti A, Pintado M, Carvalho J, Malcata F. Antiulcerogenic activity of peptide concentrates obtained from hydrolysis of whey proteins by proteases from Cynara cardunculus. Int Dairy J 2011. [DOI: 10.1016/j.idairyj.2011.06.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Junqueira-Júnior J, Junqueira AFTA, Medeiros JVR, Barbosa SHB, Nogueira ACP, Mota JMSC, Santana APM, Brito GAC, Ribeiro RA, Lima-Júnior RCP, Souza MHLP. Role of capsaicin-sensitive primary afferent neurons and non-protein sulphydryl groups on gastroprotective effect of amifostine against ethanol-induced gastric damage in rats. Dig Dis Sci 2011; 56:314-22. [PMID: 20552398 DOI: 10.1007/s10620-010-1300-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2009] [Accepted: 06/03/2010] [Indexed: 02/06/2023]
Abstract
BACKGROUND Amifostine has been widely tested as a cytoprotective agent against a number of aggressors in different organs. Recently, a gastroprotective effect was observed for this drug in a model of indomethacin-induced gastric injury. Our objective was to investigate the effect of amifostine on ethanol-induced gastric injury and the role played in this mechanism by afferent sensory neurons, non-protein sulfhydryl groups, nitric oxide, ATP-sensitive potassium channels, and cyclooxygenase-2. METHODS Rats were treated with amifostine (22.5, 45, 90, or 180 mg/kg, PO or SC). After 30 min, the rats received absolute ethanol (5 ml kg(-1), PO). One hour later, gastric damage was quantified with a planimeter. Samples from the stomach were also taken for histopathological assessment and for assays of non-protein sulfhydryl groups. The other groups were pretreated with L-NAME (10 mg kg(-1), IP), glibenclamide (10 mg kg(-1), PO), or celecoxib (10 mg kg(-1), PO). After 30 min, the animals were given amifostine (90 mg kg(-1), PO or SC), followed 30 min later by gavage with absolute ethanol (5 ml kg(-1)). Other rats were desensitized with capsaicin (125 mg kg(-1), SC) 8 days prior to amifostine treatment. RESULTS Amifostine administration PO and SC significantly and dose-dependently reduced ethanol-induced macroscopic and microscopic gastric damage by restoring glutathione levels in the stomach mucosa. Amifostine-promoted gastroprotection against ethanol-induced stomach injury was reversed by pretreatment with neurotoxic doses of capsaicin, but not by L-NAME, glibenclamide, or celecoxib. CONCLUSIONS Amifostine protects against ethanol-induced gastric injury by increasing glutathione levels and stimulating the afferent sensory neurons in the stomach.
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Affiliation(s)
- Jerônimo Junqueira-Júnior
- Brazilian Semi-Arid Institute of Biomedicine (INCT-IBISAB), Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil
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Song JY, Choi YJ, Kim JM, Kim YR, Jo JS, Park JS, Park HJ, Song YG, Lee KH, Kang HL, Baik SC, Youn HS, Cho MJ, Rhee KH, Lee WK. Purification and Characterization ofHelicobacter pyloriγ-Glutamyltranspeptidase. ACTA ACUST UNITED AC 2011. [DOI: 10.4167/jbv.2011.41.4.255] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Affiliation(s)
- Jae-Young Song
- Department of Microbiology, Gyeongsang National University School of Medicine, Jinju, Korea
- Research Institute of Life Science, Gyeongsang National University, Jinju, Korea
| | - Yeo-Jeong Choi
- Department of Microbiology, Gyeongsang National University School of Medicine, Jinju, Korea
- Research Institute of Life Science, Gyeongsang National University, Jinju, Korea
| | - Jeong-Min Kim
- Department of Microbiology, Gyeongsang National University School of Medicine, Jinju, Korea
- Research Institute of Life Science, Gyeongsang National University, Jinju, Korea
| | - Yoo-Ree Kim
- Department of Microbiology, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Jin-Seong Jo
- Department of Microbiology, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Jin-Sik Park
- Department of Microbiology, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Hee-Jin Park
- Department of Microbiology, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Yun-Gyu Song
- Department of Microbiology, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Kon-Ho Lee
- Department of Microbiology, Gyeongsang National University School of Medicine, Jinju, Korea
- Institute of Health Sciences, Gyeongsang National University, Jinju, Korea
| | - Hyung-Lyun Kang
- Department of Microbiology, Gyeongsang National University School of Medicine, Jinju, Korea
- Institute of Health Sciences, Gyeongsang National University, Jinju, Korea
- Research Institute of Life Science, Gyeongsang National University, Jinju, Korea
| | - Seung-Chul Baik
- Department of Microbiology, Gyeongsang National University School of Medicine, Jinju, Korea
- Institute of Health Sciences, Gyeongsang National University, Jinju, Korea
- Research Institute of Life Science, Gyeongsang National University, Jinju, Korea
| | - Hee-Shang Youn
- Department of Pediatrics, Gyeongsang National University School of Medicine, Jinju, Korea
- Institute of Health Sciences, Gyeongsang National University, Jinju, Korea
| | - Myung-Je Cho
- Department of Microbiology, Gyeongsang National University School of Medicine, Jinju, Korea
- Institute of Health Sciences, Gyeongsang National University, Jinju, Korea
- Research Institute of Life Science, Gyeongsang National University, Jinju, Korea
| | - Kwang-Ho Rhee
- Department of Microbiology, Gyeongsang National University School of Medicine, Jinju, Korea
- Institute of Health Sciences, Gyeongsang National University, Jinju, Korea
- Research Institute of Life Science, Gyeongsang National University, Jinju, Korea
| | - Woo-Kon Lee
- Department of Microbiology, Gyeongsang National University School of Medicine, Jinju, Korea
- Institute of Health Sciences, Gyeongsang National University, Jinju, Korea
- Research Institute of Life Science, Gyeongsang National University, Jinju, Korea
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Sener G, Sehirli O, Ipçi Y, Ercan F, Sirvanci S, Gedik N, Yeğen BC. Aqueous garlic extract alleviates ischaemia-reperfusion-induced oxidative hepatic injury in rats. J Pharm Pharmacol 2010; 57:145-50. [PMID: 15639002 DOI: 10.1211/0022357055209] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
Abstract
This study was designed to examine the effects of aqueous garlic extract (AGE) on hepatic ischaemia-reperfusion (I/R) injury in rats. For this purpose, Wistar albino rats were subjected to 45 min of hepatic ischaemia, followed by a 60-min reperfusion period. AGE (1 mL kg−1, i.p., corresponding to 500 mg kg−1) or saline was administered twice, 15 min before ischaemia and immediately before the reperfusion period. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were determined to assess liver functions. Liver tissues were taken for the determination of malondialdehyde (MDA) levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant; and myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. Hepatic collagen content, as a fibrosis marker, was also determined. Plasma ALT and AST activities were elevated in the I/R group as compared with the control group, while these increases were significantly decreased by AGE treatment. Hepatic GSH levels, significantly depressed by I/R, were elevated back to control levels in the AGE-treated I/R group. Increases in tissue MDA levels and MPO activity due to I/R injury were reduced back to control levels by AGE treatment. Similarly, increased hepatic collagen content in the I/R group was reduced to the control level with AGE treatment. Since AGE administration alleviated the I/R-induced injury of the liver and improved the hepatic structure and function, it seems likely that AGE, with its antioxidant and oxidant-scavenging properties, may be of potential therapeutic value in protecting the liver against oxidative injury due to ischaemia-reperfusion.
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Affiliation(s)
- Göksel Sener
- Department of Pharmacology, Marmara University School of Pharmacy, Tibbiye Cad. 34668 Istanbul, Turkey.
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Castro G, Carvalho J, Tinti S, Possenti A, Sgarbieri V. Anti-Ulcerogenic Effect of a Whey Protein Isolate and Collagen Hydrolysates Against Ethanol Ulcerative Lesions on Oral Administration to Rats. J Med Food 2010; 13:83-90. [DOI: 10.1089/jmf.2008.0277] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- G.A. Castro
- Departamento de Alimentos e Nutrição, Faculdade de Engenharia de Alimentos, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil
| | - J.E. Carvalho
- Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil
| | - S.V. Tinti
- Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil
| | - A. Possenti
- Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil
| | - V.C. Sgarbieri
- Departamento de Alimentos e Nutrição, Faculdade de Engenharia de Alimentos, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil
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Bostanci EB, Yol S, Teke Z, Kayaalp C, Sakaogullari Z, Ozel Turkcu U, Bilgihan A, Akoglu M. Effects of carbon dioxide pneumoperitoneum on hepatic function in obstructive jaundice: an experimental study in a rat model. Langenbecks Arch Surg 2009; 395:667-76. [PMID: 20012315 DOI: 10.1007/s00423-009-0577-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2009] [Accepted: 11/15/2009] [Indexed: 11/29/2022]
Abstract
BACKGROUND AND AIMS The physiology of the patient during laparoscopy differs from that of open surgery. Both pneumoperitoneum and obstructive jaundice impair the hepatic function, but the combined insult has not been previously examined. In this study, we aimed to investigate the effects of carbon dioxide (CO(2)) pneumoperitoneum on hepatic function in a rat model of obstructive jaundice. METHODS Forty-four male Sprague-Dawley rats were divided into four groups: group 1 (n = 10), sham-operated group; group 2 (n = 12), obstructive jaundice group; group 3 (n = 10), CO(2) pneumoperitoneum group; and group 4 (n = 12), obstructive jaundice and CO(2) pneumoperitoneum group. Common bile duct was ligated and divided in the obstructive jaundice groups. After 6 days, a 12-mmHg pneumoperitoneum was induced, maintained for 60 min, and released for 120 min. Blood samples were drawn for the measurement of white blood cell and platelet counts, serum liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin). Tissue samples were obtained for analyses of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) levels. We evaluated the degree of liver injury on a grading scale from 0 to 4, histopathologically. RESULTS Pneumoperitoneum after biliary obstruction resulted in an increase in AST and ALT levels and a decrease in white blood cell and platelet counts. However, changes in liver tissue MDA, GSH, and SOD levels did not correlate with the changes in AST and ALT levels and white blood cell and platelet counts. After sham operation with pneumoperitoneum, the GSH levels in liver homogenate were significantly decreased in the group 3 when compared to the group 2. On the other hand, obstructive jaundice itself caused significant reduction in the SOD activity of liver homogenate in comparison to the group 3. Histopathologically, sinusoidal congestion and vacuolization were more severe in the group 3. CONCLUSIONS Alterations in hepatic function occur in pneumoperitoneum applied jaundiced subjects. However, there were no statistically significant differences between the groups 2 and 4 with regard to white blood cell and platelet counts, serum liver enzymes including AST, ALT, and total bilirubin values, MDA and GSH levels and SOD activity of liver homogenate, and histologic damage. These results indicate that there is no additional risk on liver function associated with pneumoperitoneum performed in obstructive jaundice.
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Affiliation(s)
- Erdal Birol Bostanci
- Department of Gastroenterological Surgery, Turkey Yuksek Ihtisas Teaching and Research Hospital, Ankara, Turkey.
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Ligha A, Fawehinmi H. Protection by Liquorice in Alcohol Induced Gastric Mucosa Damage. ACTA ACUST UNITED AC 2009. [DOI: 10.3923/pjn.2009.1532.1536] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Effect of melatonin on burn-induced gastric mucosal injury in rats. Burns 2009; 35:863-8. [PMID: 19477599 DOI: 10.1016/j.burns.2008.09.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2008] [Accepted: 09/04/2008] [Indexed: 11/22/2022]
Abstract
We studied the effect of melatonin treatment on gastric mucosal damage induced by experimental burns and its possible relation to changes in gastric lipid peroxidation status. Melatonin was intraperitoneally applied immediately after third-degree burns over 30% of total body skin surface area of rats. Malondialdehyde (MDA), uric acid (UA) and sulphydril (SH) levels were determined in gastric mucosa and blood plasma and used as biomarkers of the oxidative stress. The results showed that the skin burn caused oxidative stress evidenced by accumulation of MDA and UA as well as the depletion of SHs in gastric mucosa. Plasma MDA concentrations were elevated, while plasma SH concentrations were decreased after burns. Melatonin (10 mg per kg body weight) protected gastric mucosa from oxidative damage by suppressing lipid peroxidation and activating the antioxidant defence. It may be hypothesised that melatonin restores the redox balance in the gastric mucosa and protects it from burn-induced oxidative injury. Melatonin has no significant influence on the concentrations of plasma MDA and antioxidants after burn; therefore, it should largely be considered as a limiting factor for tissue-damage.
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Ewertowska M, Jodynis-Liebert J, Kujawska M, Adamska T, Matławska I, Szaufer-Hajdrych M. Effect of Aquilegia vulgaris (L.) ethyl ether extract on liver antioxidant defense system in rats. Int J Occup Med Environ Health 2009; 22:115-123. [PMID: 19617191 DOI: 10.2478/v10001-009-0016-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
INTRODUCTION The ethyl ether extract from Aquilegia vulgaris (L.) (Ranunculaceae) contains a lot of phenolic acids. Their hydroxyl groups are capable of donating hydrogen atoms at the initial stage of lipid peroxidation (LPO), which inactivates hydroxyperoxides formed from polyunsaturated fatty acids (PUFAs) and leads to breakdown of the propagation chain. MATERIAL AND METHODS Rats pretreated with acetaminophen (APAP) (600 mg/kg b.w., p.o.) were given ethyl ether extract (100 mg/kg b.w., p.o.) obtained from A. vulgaris herb. The study parameters measured were microsomal lipid peroxidation, reduced glutathione, and the activity of hepatic antioxidant enzymes and some drug metabolizing enzymes. RESULTS The treatment with ethyl ether extract of the herb produced a 87-95% decrease in uninduced and Fe2+/ascorbate-stimulated microsomal lipid peroxidation in the liver of rats receiving APAP. Hepatic glutathione level depleted by APAP increased significantly (by 18%) after the extract treatment. Antioxidant enzyme activity in the liver, inhibited by APAP, was found to increase after administration of the extract: catalase by about 36%, glutathione reductase by 27% and glutathione S-transferase by 29%. Glucose-6-phosphate dehydrogenase, which decreased after APAP administration, increased again by 26% after extract treatment. The extract tested did not affect the activity of DT-diaphorase. The cytochrome P450 content, depleted by APAP, increased as much as by 100% after the treatment. The activities of NADPH-cytochrome P450 reductase, aniline hydroxylase and aminopyrine N-demethylase were not affected. CONCLUSIONS The protective effect of the Aquilegia vulgaris extract in APAP-induced liver injury was mediated by its antioxidant activity. The extract did not inhibit the formation of reactive intermediate metabolites of APAP.
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Ineu R, Pereira M, Aschner M, Nogueira C, Zeni G, Rocha J. Diphenyl diselenide reverses gastric lesions in rats: Involvement of oxidative stress. Food Chem Toxicol 2008; 46:3023-9. [DOI: 10.1016/j.fct.2008.06.007] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2007] [Revised: 05/26/2008] [Accepted: 06/03/2008] [Indexed: 12/18/2022]
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Elseweidy MM, Younis NN, Amin RS, Abdallah FR, Fathy AM, Yousif ZA. Effect of some natural products either alone or in combination on gastritis induced in experimental rats. Dig Dis Sci 2008; 53:1774-1784. [PMID: 18368490 DOI: 10.1007/s10620-008-0246-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2004] [Accepted: 07/12/2005] [Indexed: 02/08/2023]
Abstract
Gastritis, an inflammatory state in gastric mucosa, can be induced experimentally in various ways. The present study considered the iodoacetamide model (Iodo). Omega-3 fatty acids (fish oil), black seed oil, and curcuminoids (natural products) in addition to omeprazole (synthetic proton-pump inhibitor) were tested. Supplementation of 0.1% iodoacetamide to drinking water of experimental rats for two consecutive weeks resulted in: (i) increased serum nitric oxide (NO) and gastrin, and decreased pepsinogen, (ii) depletion of gastric mucosal glutathione (GSH), and (iii) increased gastric mucosal lipid peroxidation (MDA), but failed to affect gastric mucosal myeloperoxidase (MPO) activity. Histological examination showed marked neutrophilic infiltration after 1 week of iodoacetamide administration and shedding of apical cell layer with pale edematous vacuolated gastric gland cells and thickening of muscularis mucosa after 2 weeks of iodoacetamide intake. Individual administration of omega-3 fatty acids 12 mg/kg, black seed oil 50 mg/kg, and curcuminoids 50 mg/kg body weight orally daily for 3 weeks decreased MDA, gastrin, and NO, and normalized mucosal GSH but failed to affect serum pepsinogen level. Combined administration of these natural products for 3 weeks normalized MPO activity, and other effects were nearly the same as with individual use. Omeprazole administration 30 mg/kg body weight orally daily for 3 weeks induced a similar response except for an observed increase in serum gastrin and pepsinogen levels.
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Affiliation(s)
- Mohamed M Elseweidy
- Biochemistry Department, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
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El Shenawy NS, Soliman MFM, Reyad SI. The effect of antioxidant properties of aqueous garlic extract and Nigella sativa as anti-schistosomiasis agents in mice. Rev Inst Med Trop Sao Paulo 2008; 50:29-36. [PMID: 18327484 DOI: 10.1590/s0036-46652008000100007] [Citation(s) in RCA: 71] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2007] [Accepted: 09/11/2007] [Indexed: 11/22/2022] Open
Abstract
The aim of this study was to assess the antioxidant and anti-schistosomal activities of the garlic extract (AGE) and Nigella sativa oil (NSO) on normal and Schistosoma mansoni-infected mice. AGE (125 mg kg-1, i.p.) and NSO (0.2 mg kg-1, i.p.) were administrated separately or in combination for successive 28 days, starting from the 1st day post infection (pi). All mice were sacrificed at weeks 7 pi. Hematological and biochemical parameters including liver and kidney functions were measured to assess the progress of anemia, and the possibility of the tissue damage. Serum total protein level, albumin, globulin and cholesterol were also determined. Malondialdehyde (MDA) and glutathione (GSH) levels were determined in the liver tissues as biomarkers for oxidative and reducing status, respectively. The possible effect of the treatment regimens on Schistosoma worms was evaluated by recording percentage of the recovered worms, tissue egg and oogram pattern. Result showed that, protection with AGE and NSO prevented most of the hematological and biochemical changes and markedly improved the antioxidant capacity of schistosomiasis mice compared to the infected-untreated ones. In addition, remarkable reduction in worms, tissue eggs and alteration in oogram pattern were recorded in all the treated groups. The antioxidant and antischistosomal action of AGE and NSO was greatly diverse according to treatment regimens. These data point to these compounds as promising agents to complement schistosomiasis specific treatment.
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Affiliation(s)
- Nahla S El Shenawy
- Zoology Department, Faculty of Science, Suez Canal University, Ismailia, Egypt.
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Kamath BS, Srikanta BM, Dharmesh SM, Sarada R, Ravishankar GA. Ulcer preventive and antioxidative properties of astaxanthin from Haematococcus pluvialis. Eur J Pharmacol 2008; 590:387-95. [PMID: 18602387 DOI: 10.1016/j.ejphar.2008.06.042] [Citation(s) in RCA: 86] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2008] [Revised: 05/09/2008] [Accepted: 06/03/2008] [Indexed: 12/21/2022]
Abstract
The anti-ulcer properties of astaxanthin fractions such as total carotenoid and astaxanthin esters from Haematococcus pluvialis were evaluated in ethanol-induced gastric ulcers in rats. Since oxygen radical release is a pathogenic factor of ethanol-induced gastric damage, astaxanthin - a free radical scavenger, was investigated as a potential ulcer preventive agent. Astaxanthin fractions - total carotenoid and astaxanthin esters were orally administered to experimental rats at 100, 250 and 500 microg/kg b.w. prior to ulcer induction. Alcian blue binding assay indicates that, total carotenoid and astaxanthin esters at 500 microg/kg b.w could protect gastric mucin approximately 40% and 67% respectively. Pre-treatment with astaxanthin esters, also resulted in significant increase in antioxidant enzyme levels - catalase, superoxide dismutase, and glutathione peroxidase in stomach homogenate. Histopathological examination substantiated the protective effect of astaxanthin in pre-treated rats. The increased antioxidant potencies such as free radical scavenging activity with an IC(50) of approximately 8 microg/ml and reducing power abilities (59 x 10(3) U/g) in vitro, reveal that H. pluvialis astaxanthin may protect gastric mucosal injury by antioxidative mechanism. In addition, approximately 23 fold increased lipoxygenase-inhibitory property, in comparison with standard astaxanthin and significant H(+), K(+)-ATPase-inhibitory activity of astaxanthin esters, in comparison with known proton pump blocking anti-ulcer drug - omeprazole, may envisage the potential gastroprotective effect by regulating the gastric mucosal injury and gastric acid secretion by the gastric cell during ulcer disease.
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Affiliation(s)
- Burde Sandesh Kamath
- Plant Cell Biotechnology Department, Central Food Technological Research Institute, Mysore, 570 020, India
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Park SW, Oh TY, Kim YS, Sim H, Park SJ, Jang EJ, Park JS, Baik HW, Hahm KB. Artemisia asiatica extracts protect against ethanol-induced injury in gastric mucosa of rats. J Gastroenterol Hepatol 2008; 23:976-84. [PMID: 18444990 DOI: 10.1111/j.1440-1746.2008.05333.x] [Citation(s) in RCA: 75] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Based on our previous studies that Artemisia asiatica extracts exert either antioxidative or cytoprotective actions against non-steroidal anti-inflammatory drugs or Helicobacter pylori-induced gastric mucosal injury, or imposes qualified ulcer healing in an acetic acid-induced gastric ulcer model, we investigated the protective effects of Artemisia asiatica extracts against ethanol-induced gastric mucosal injury. METHODS Sprague-Dawley rats received 4 g/kg body weight (BW) of absolute ethanol intragastrically, which produced visible hemorrhagic gastric lesions 60 min later. RESULTS In this animal setting, the pretreatment of Artemisia extracts (30 or 100 mg/kg BW), 1 h before ethanol administration, significantly attenuated the source of gastric injury, which was assessed with gross and microscopic analysis (P < 0.01). Protection from alcohol-induced damage with Artemisia pretreatment was associated with significantly decreased lipid peroxidation, protecting gastric mucosa from glutathione depletion, as well as the inhibition of the cytochrome 2E1 ethanol-metabolizing enzyme. It attenuated the expressions of ethanol-induced pro-inflammatory cytokines, including interleukin (IL)-1beta and interferon-gamma, a weak activation of IL-10, the inhibition of the alcohol-induced overexpression of intercellular adhesion molecule-1, and the considerable induction of heat shock protein-72 expression in gastric mucosal homogenates. CONCLUSION The data suggest that the ethanol extracts of Artemisia asiatica exerted significant protection from alcohol-induced gastric mucosal injury through bio-regulation, which is essential for cytoprotection and anti-inflammation.
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Affiliation(s)
- Sang Woon Park
- Digestive Disease Center and DMC-MECOX Biomedical Research Center, Jesaeng Hospital, Seongnam, Korea
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Nagy L, Nagata M, Szabo S. Protein and non-protein sulfhydryls and disulfides in gastric mucosa and liver after gastrotoxic chemicals and sucralfate: Possible new targets of pharmacologic agents. World J Gastroenterol 2007; 13:2053-60. [PMID: 17465447 PMCID: PMC4319124 DOI: 10.3748/wjg.v13.i14.2053] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
AIM: To investigate the role of major non-protein and protein sulfhydryls and disulfides in chemically induced gastric hemorrhagic mucosal lesions (HML) and the mechanism of gastroprotective effect of sucralfate.
METHODS: Rats were given 1 mL of 75% ethanol, 25% NaCl, 0.6 mol/L HCl, 0.2 mol/L NaOH or 1% ammonia solutions intragastrically (i.g.) and sacrificed 1, 3, 6 or 12 min later. Total (reduced and oxidized) glutathione (GSH + GSSG), glutathione disulfide (GSSG), protein free sulfhydryls (PSH), protein-glutathione mixed disulfides (PSSG) and protein cystine disulfides (PSSP) were measured in gastric mucosa and liver.
RESULTS: Reduced glutathione (GSH) was depleted in the gastric mucosa after ethanol, HCl or NaCl exposure, while oxidized glutathione (GSSG) concentrations increased, except by HCl and NaOH exposure. Decreased levels of PSH after exposure to ethanol were observed, NaCl or NaOH while the total protein disulfides were increased. Ratios of reduced to oxidized glutathione or sulfhydrils to disulfides were decreased by all chemicals. No changes in thiol homeostasis were detected in the liver after i.g. abbreviation should be spelled out the first time here administration of ethanol. Sucralfate increased the concentrations of GSH and PSH and prevented the ethanol-induced changes in gastric mucosal thiol concentrations.
CONCLUSION: Our modified methods are now suitable for direct measurements of major protein and non-protein thiols/disulfides in the gastric mucosa or liver. A common element in the pathogenesis of chemically induced HML and in the mechanism of gastroprotective drugs seems to be the decreased ratios of reduced and oxidized glutathione as well as protein sulfhydryls and disulfides.
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Affiliation(s)
- Lajos Nagy
- Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
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Castro GA, Sgarbieri VC, Carvalho JE, Tinti SV, Possenti A. Protective Effect of Collagen Derivates on the Ulcerative Lesions Caused by Oral Administration of Ethanol. J Med Food 2007; 10:154-8. [PMID: 17472480 DOI: 10.1089/jmf.2006.262] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
The protective effect of beef and pig collagen hydrolysates and their fractions were tested as anti-ulcerogenic agents in rats (weighing 250-350 g) against ulcerative lesions caused by ethanol. Beef and pig collagen hydrolysates were fractionated by ultrafiltration into different molecular weight fractions. The protocol employed a negative and a positive control and a single dose of the experimental samples given by intragastric intubation. The beef collagen did not present a dose-response correlation in the ethanol model, whereas pig collagen showed a logarithmic dose-response relationship. Beef collagen hydrolysate decreased the ulcerative lesion index of 55% versus a 61% decrease for pig collagen hydrolysate at the same dosage (750 mg/kg of body weight). No significant differences were found (P > .05) between the hydrolysates and their fractions.
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Affiliation(s)
- G A Castro
- Departamento de Alimentos e Nutrição, Faculdade de Engenharia de Alimentos, Universidade Estadual de Campinas, Campinas, São Paulo, Brasil
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Dulundu E, Ozel Y, Topaloglu U, Sehirli O, Ercan F, Gedik N, Sener G. Alpha-lipoic acid protects against hepatic ischemia-reperfusion injury in rats. Pharmacology 2007; 79:163-70. [PMID: 17259747 DOI: 10.1159/000098953] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2006] [Accepted: 10/17/2006] [Indexed: 01/26/2023]
Abstract
BACKGROUND AND AIM To evaluate the protective effect of alpha-lipoic acid in reducing oxidative damage after severe hepatic ischemia/reperfusion (IR) injury. METHODS Wistar albino rats were subjected to 45 min of hepatic ischemia, followed by 60 min reperfusion period. Lipoic acid (100 mg/kg i.p.) was administered 15 min prior to ischemia and immediately before reperfusion period. At the end of the reperfusion period aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) activity, and cytokine, TNF-alpha and IL-1beta levels were determined in serum samples. Malondialdehyde (MDA), and glutathione (GSH) levels and myeloperoxidase (MPO) activity were determined in the liver tissue samples while formation of reactive oxygen species was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes. Tissues were also analyzed histologically. RESULTS Serum ALT, AST, and LDH activities and TNF-alpha and IL-1beta levels were elevated in the I/R group, while this increase was significantly lower in the group of animals treated concomitantly with lipoic acid. Hepatic GSH levels, significantly depressed by I/R, were elevated back to control levels in lipoic acid-treated I/R group. Furthermore, increases in tissue luminol and lucigenin CL, MDA levels and MPO activity due to I/R injury were reduced back to control levels with lipoic acid treatment. CONCLUSION Since lipoic acid administration alleviated the I/R-induced liver injury and improved the hepatic structure and function, it seems likely that lipoic acid with its antioxidant and oxidant-scavenging properties may be of potential therapeutic value in protecting the liver against oxidative injury due to ischemia-reperfusion.
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Affiliation(s)
- Ender Dulundu
- Department of 5th Surgery, Haydarpasa Numune Educational and Research Hospital, Istanbul, Turkey
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Mota JMSC, Soares PMG, Menezes AAJ, Lemos HP, Cunha FQ, Brito GAC, Ribeiro RA, de Souza MHLP. Amifostine (Wr-2721) prevents indomethacin-induced gastric damage in rats: role of non-protein sulfhydryl groups and leukocyte adherence. Dig Dis Sci 2007; 52:119-25. [PMID: 17160473 DOI: 10.1007/s10620-006-9496-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2006] [Accepted: 06/19/2006] [Indexed: 12/09/2022]
Abstract
This study was designed to evaluate the protective effect of amifostine on indomethacin-induced gastric damage, and the role of increased gastric non-protein sulfhydryl groups (NP-SH) and decreased leukocyte adherence in this event. Wistar rats were pretreated with amifostine (10, 30, or 90 mg/kg intraperitoneal (i.p.) or subcutaneous (s.c.)) or saline. After 30 min, the rats received indomethacin (20 mg/kg, by gavage) and were then killed 3 hr later. Macroscopic and microscopic gastric damage, concentration of gastric NP-SH, prostaglandin E2 (PGE2), and mesenteric leukocyte adherence (intravital microscopy) were assessed. Amifostine prevented significantly (P < 0.05), macroscopic or microscopic, indomethacin-induced gastric damage, and increased gastric NP-SH, in a dose-dependent manner, with a maximal effect at a dose of 90 mg/kg. Subcutaneous, but not i.p., amifostine administration decreased (P < 0.05) the indomethacin-induced increase in leukocyte adherence. Indomethacin-induced PGE2 depletion was not reversed by amifostine. Amifostine has a protective effect against indomethacin-induced gastropathy by increasing gastric NP-SH and decreasing leukocyte adherence.
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Affiliation(s)
- José Maurício S C Mota
- Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
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Mezzaroba L, Carvalho J, Ponezi A, Antônio M, Monteiro K, Possenti A, Sgarbieri V. Antiulcerative properties of bovine α-lactalbumin. Int Dairy J 2006. [DOI: 10.1016/j.idairyj.2005.10.027] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Toklu HZ, Sehirli AO, Velioğlu-Oğünç A, Cetinel S, Sener G. Acetaminophen-induced toxicity is prevented by β-d-glucan treatment in mice. Eur J Pharmacol 2006; 543:133-40. [PMID: 16822497 DOI: 10.1016/j.ejphar.2006.05.033] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2005] [Revised: 05/17/2006] [Accepted: 05/18/2006] [Indexed: 11/19/2022]
Abstract
The protective effect of beta-glucan against oxidative injury caused by acetaminophen was studied in mice liver. BALB-c mice (25-30 g) were pre-treated with beta-d-glucan (50 mg/kg, p.o.) for 10 days and on the 11th day they received an overdose of acetaminophen (900 mg/kg, i.p.). Four hours after the acetaminophen injection, mice were decapitated and their blood was taken to determine serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and tumor necrosis factor-alpha (TNF-alpha) levels. Tissue samples of the liver were taken for histological examination or for the determination of levels of malondialdehyde, an end product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase activity, an index of tissue neutrophil infiltration. The formation of reactive oxygen species in hepatic tissue samples was monitored by using the chemiluminescence technique with luminol and lucigenin probes. Acetaminophen caused a significant decrease in the GSH level of the tissue, which was accompanied with significant increases in the hepatic luminol and lucigenin chemiluminescence values, malondialdehyde level, MPO activity and collagen content. Similarly, serum ALT, AST levels, as well as LDH and TNF-alpha, were elevated in the acetaminophen-treated group when compared with the control group. On the other hand, beta-d-glucan treatment reversed all these biochemical indices, as well as histopathological alterations that were induced by acetaminophen. In conclusion, these results suggest that beta-d-glucan exerts cytoprotective effects against oxidative injury through its antioxidant properties and may be of therapeutic use in preventing acetaminophen toxicity.
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Affiliation(s)
- Hale Z Toklu
- Marmara University, School of Pharmacy, Department of Pharmacology, Istanbul, Turkey
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