Hepatoprotective effects of misoprostol and silymarin on carbon tetrachloride-induced hepatic damage in rats.
The aim of this study was to investigate the effect of misoprostol, silymarin or the co-administration of misoprostol + silymarin on the carbon tetrachloride (CCl(4))-induced hepatic injury in rats. Misoprostol (10, 100, 1000 microg/kg), silymarin (25 mg/kg) or misoprostol (100 microg/kg) + silymarin (25 mg/kg) was given once daily orally simultaneously with CCl(4) and for 15 days thereafter. The results showed that misoprostol (10, 100 or 1000 microg/kg) conferred significant protection against the hepatotoxic actions of CCl(4) in rats, reducing serum alanine aminotransferase (ALT) levels by 24.7%, 42.6% and 49.4%, respectively compared with controls. Misoprostol, given at 100 or 1000 microg/kg, decreased aspartate aminotransferase (AST) by 28 and 43.6% and alkaline phosphatase (ALP) by 19.3% and 53.4% respectively. Meanwhile, silymarin reduced ALT, AST and ALP levels by 62.7%, 66.1% and 65.1% respectively. The co-administration of misoprostol (100 microg/kg) and silymarin (25 mg/kg) resulted in 61.4%, 66.1% and 57.5% reduction in ALT, AST and ALP levels respectively. Histopathological alterations and depletion of hepatocyte glycogen and DNA content by CCl(4) were markedly reduced after treatment with misoprostol, silymarin or misoprostol + silymarin. Image analysis of liver specimens revealed a marked reduction in liver necrosis; area of damage: 32.4%, 24% and 10.2% after misoprostol (10, 100 or 1000 microg/kg), 7.2% after silymarin and 10.9% after treatment with misoprostol 100 microg/kg + silymarin, compared with CCl(4) control group (46.7%). These results indicate that treatment with misoprostol protects against hepatocellular necrosis induced by CCl(4). This study suggests a potential therapeutic use for misoprostol in liver injury.
Salam
Omar M E Abdel
OM
Department of Pharmacology, National Research Centre, Dokki, Cairo, Egypt. omasalam@hotmail.com
Sleem
Amany A
AA
Omara
Enayat A
EA
Hassan
Nabila S
NS
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006003:Glycogen / Q000378:metabolism; D008107:Liver Diseases / Q000517:prevention & control*; D008111:Liver Function Tests; D008297:Male; D016595:Misoprostol / Q000008:administration & dosage / Q000494:pharmacology*; D009336:Necrosis / Q000139:chemically induced / Q000517:prevention & control; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012838:Silymarin / Q000008:administration & dosage / Q000494:pharmacology*
D020011:Protective Agents; D012838:Silymarin; D016595:Misoprostol; D006003:Glycogen; D004247:DNA; D002251:Carbon Tetrachloride