title: Aminoguanidine potentiates the hepatoprotective effect of silymarin in CCL4 treated rats.
abstract: This study examined the possible hepatoprotective effect of aminoguanidine in comparison with silymarin and investigated the possible beneficial effects of the combination of aminoguanidine and silymarin on CCL4-induced liver fibrosis. Male Wister albino rats were randomly divided into five groups (10 rats/group). Group I included control rats injected only with liquid paraffin and saline; group II represents CCL(4) control (injected with CCL(4) 3 times a week for 6 weeks in a dose of 25μl/100gm.b.w i.p, diluted 1:6 with liquid paraffin); group III treated with aminoguanidine (100 mg/kg); group IV was given silymarin (100 mg/kg); group V was given aminoguanidine (100 mg/kg) and silymarin (100 mg/kg). Fibrosis was depicted histologically and biochemically. CCL4 increased serum liver enzymes (ALT, AST, and ALP), lactate dehydrogenase (LDH), level of nitric oxide (NO), tumor necrosis factor alpha (TNFα) and liver malondialdehyde content (MDA), collagen fiber percent and decreased liver reduced glutathione (GSH) content as endogenous antioxidant. Histopathological changes induced by CCL4 include regenerative nodules, deteriorated parenchyma; the lobules were infiltrated with fat and structurally altered. Aminoguanidine, silymarin and their combination reduced these changes and attenuated the pathological effects of CCL(4) induced liver injury. The combination of both drugs was better than each drug alone. It is concluded that aminoguanidine has protective effect against CCL(4) induced hepatoxicity via its iNOS inhibition and antioxidant effects. In addition, the combination of AG with silymarin has more potent hepatoprotective effect than each drug alone.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Zagazig University Egypt, Egypt.
authors.forename: Ahmed Fahmy
authors.initials: AF
authors.lastname: Ahmed
authors.forename: Mona Fouad
authors.initials: MF
authors.lastname: Mahmoud
authors.forename: Marwa Arafat
authors.initials: MA
authors.lastname: Ouf
authors.forename: Eman Abd
authors.initials: EA
authors.lastname: El-Fathaah
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012838:Silymarin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D006146:Guanidines; D020011:Protective Agents; D012838:Silymarin; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen; D002251:Carbon Tetrachloride; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine