Effect of ghrelin on chronic liver injury and fibrogenesis in male rats: Possible role of nitric oxide |
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| Institution: | 1. Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt;2. Department of Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt;3. Department of Pharmacology, National Research Center, Cairo, Egypt;4. Departments of Anesthesia, Pain Management and Perioperative Medicine''s, Faculty of Medicine, Dalhousie University, Halifax, Canada;5. Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Canada;6. Department of Pharmacology, Faculty of Medicine, Dalhousie University, Halifax, Canada;1. Department of Chemistry, University of Girona, C/M.Aurèlia Campmany 69, 17003 Girona, Spain;2. Department of Physics, The University of the West Indies, Mona, Kingston 7, Jamaica;3. Department of Obstetrics and Gynecology, The University of the West Indies, Mona, Kingston 7, Jamaica;4. Nuclear Science and Instrumentation Laboratory, IAEA Laboratories, A-2444 Seibersdorf, Austria;5. Institute of Nuclear and Particle Physics, National Center for Scientific Research “Demokritos”, 153 10 Aghia Paraskevi, Athens, Greece;6. IFEG, National Scientific and Technical Research Council (CONICET), X5000HUA, Córdoba, Argentina;7. Institute of Environmental Assessment and Water Research, IDAEA-CSIC. Jordi Girona 18-26, 08034 Barcelona, Spain |
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| Abstract: | Recent studies have revealed that ghrelin may be an antioxidant and anti-inflammatory agent in many organs, however its role in chronic liver injury (CLI) remains unclear. The role of nitric oxide (NO) in CLI is controversial as evidence suggests that NO is either a primary mediator of liver cell injury or exhibits a protective effect against injurious stimuli. Recent evidence demonstrated that the therapeutic potential for ghrelin was through eNOS activation and increase in NO production. However, its role on NO production in the liver has not been previously investigated. The aim of this study was to investigate the role of ghrelin in treatment of CLI, and whether this action is mediated through NO. Forty male rats were divided into four groups: Group I: Control; Group II: chronic liver injury (CLI); Group III: CLI + Ghrelin; and Group IV: CLI + Ghrelin + l-NAME. Liver enzymes and tumor necrosis factor alpha (TNF-α), were measured to assess hepatocellular injury. Liver tissue collagen content, malondialdehyde (MDA), gene expression of Bax, Bcl-2, and eNOS were assessed to determine the mechanism of ghrelin action. Results showed that ghrelin decreased serum liver enzymes and TNF-α levels. Ghrelin also reduced liver tissue collagen, MDA, and Bax gene expression, and increased Bcl-2 and eNOS gene expression. The effects on TNF-α, collagen, MDA, Bax, and eNOS were partially reversed in Group IV, suggesting that ghrelin's action could be through modulation of NO levels. Therefore, ghrelin's hepatoprotective effect is partially mediated by NO release. |
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| Keywords: | Liver injury Fibrosis Thioacetamide Ghrelin Nitric oxide |
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