title: Rebamipide retards CCl4-induced hepatic fibrosis in rats: Possible role for PGE2.
abstract: Prostaglandin E2 (PGE2) is a potent physiological suppressor of liver fibrosis. Because the anti-ulcer drug rebamipide can induce the formation of endogenous PGE2, this study investigated the potential effects of rebamipide on development of a hepatic fibrosis that was inducible by carbon tetrachloride (CCl4). Groups of Wistar rats received intraperitoneal (IP) injections of CCl4 (0.45 ml/kg [0.72 g CCl4/kg]) over the course of for 4 weeks. Sub-sets of CCl4-treated rats were also treated concurrently with rebamipide at 60 or 100 mg/kg. At 24 h after the final treatments, liver function and oxidative stress were indirectly assessed. The extent of hepatic fibrosis was evaluated using two fibrotic markers, hyaluronic acid (HA) and pro-collagen-III (Procol-III); isolated liver tissues underwent histology and were evaluated for interleukin (IL)-10 and PGE2 content. The results indicated that treatment with rebamipide significantly inhibited CCl4-induced increases in serum ALT and AST and also reduced oxidative stress induced by CCl4. Fibrotic marker assays revealed that either dose of rebamipide decreased the host levels of Procol-III and HA that had become elevated due to the CCl4. At the higher dose tested, rebamipide appeared to be able to permit the hosts to have a normal liver histology and to minimize any CCl4-induced collagen precipitation in the liver. Lastly, the use of rebamipide was seen to be associated with significant increases in liver levels of both PGE2 and the anti-inflammatory cytokine IL-10. Based on these findings, it is concluded that rebamipide can retard hepatic fibrosis induced by CCl4 and that this effect may, in part, be mediated by an induction of PGE2 and IL-10 in the liver itself.
authors: a Department of Pharmacology and Toxicology , Damanhour University , Damanhour , Egypt ;
authors: Sherin
authors: S
authors: Zakaria
authors: b Department of Pharmacology and Toxicology , Tanta University , Tanta , Egypt.
authors: Alaa
authors: A
authors: El-Sisi
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000633:toxicity; D003094:Collagen / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D004195:Disease Models, Animal; D005355:Fibrosis; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D015363:Quinolones / Q000627:therapeutic use*; D017208:Rats, Wistar; D015854:Up-Regulation
chemical_list: D000893:Anti-Inflammatory Agents; D015363:Quinolones; D016753:Interleukin-10; D003094:Collagen; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D015232:Dinoprostone; C052785:rebamipide; D000409:Alanine
keywords: Hepatic fibrosis; IL-10; PGE2; rebamipide