title: Effect of ghrelin on chronic liver injury and fibrogenesis in male rats: possible role of nitric oxide.
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.
authors: Department of Physiology, Faculty of Pharmacy & Biotechnology, German University in Cairo, Egypt. Electronic address: nashwa_kabil@hotmail.com.
authors: Nashwa N
authors: NN
authors: Kabil
authors: Department of Physiology, Kasr Al Aini Faculty of Medicine, Cairo University, Egypt. Electronic address: h.seddiek@yahoo.com.
authors: Hanan A
authors: HA
authors: Seddiek
authors: Department of Physiology, Faculty of Pharmacy & Biotechnology, German University in Cairo, Egypt; Department of Physiology, Kasr Al Aini Faculty of Medicine, Cairo University, Egypt. Electronic address: nadjayassin@yahoo.com.
authors: Nadia A
authors: NA
authors: Yassin
authors: Department of Physiology, Faculty of Pharmacy & Biotechnology, German University in Cairo, Egypt; Department of Physiology, Kasr Al Aini Faculty of Medicine, Cairo University, Egypt. Electronic address: drmahagamal@gmail.com.
authors: Maha M
authors: MM
authors: Gamal-Eldin
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D054439:Ghrelin / Q000494:pharmacology; D008099:Liver / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051381:Rats; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: C494828:Bax protein, rat; D004791:Enzyme Inhibitors; D054439:Ghrelin; D051028:bcl-2-Associated X Protein; D009569:Nitric Oxide; D008315:Malondialdehyde; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019331:NG-Nitroarginine Methyl Ester
keywords: Fibrosis; Ghrelin; Liver injury; Nitric oxide; Thioacetamide