Attenuation of hepatic fibrosis through captopril and enalapril in the livers of bile duct ligated rats.
Hepatic fibrosis is a common feature in different types of chronic liver injury. The demonstration of the pro-fibrogenesis role of angiotensin II in chronic liver diseases brought up the idea that anti-angiotensin II agents may be effective on improvement of hepatic fibrosis by either blocking the angiotensin II receptor or inhibition of angiotensin converting enzyme (ACE). This study is aimed at comparing the anti-fibrogenesis effects of two ACE inhibitors, captopril and enalapril, in the livers of rats with bile duct ligation through biochemical and histopathological parameters. Male Albino Wistar rats were divided into four groups (n=4-5 each), including sham operated, bile duct ligated, captopril and enalapril treated. After 28 days of treatment, the liver was removed and the levels of hepatic hydroxyproline, glutathione and lipid peroxidation were determined. The degree of the development of fibrosis was evaluated through histopathological numerical scores. The results demonstrated that angiotensin converting enzyme inhibitors increased GSH, decreased lipid peroxidation and improved hepatic fibrosis as shown by histopathology as well as decreased hepatic content of hydroxyproline. Enalapril was significantly more effective than captopril (p<0.001) in improvement of hepatic fibrosis. Also it was shown that enalapril has a significant antioxidative effect (p<0.05) in comparison with captopril. In conclusion, the results of our study suggest that the antifibrotic effect of enalapril may be mostly related to the inhibition of angiotensin converting enzyme.
Karimian
Golnar
G
Department of Pharmacology, School of Medicine, Medical Sciences/University of Tehran, Poursina Avenue, Tehran 13145-784, Iran.
Mohammadi-Karakani
Ali
A
Sotoudeh
Masoud
M
Ghazi-Khansari
Mahmoud
M
Ghobadi
Ghazale
G
Shakiba
Behnam
B
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001649:Bile Duct Diseases / Q000150:complications; D002216:Captopril / Q000627:therapeutic use*; D003135:Common Bile Duct; D003251:Constriction, Pathologic / Q000150:complications; D004656:Enalapril / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D008026:Ligation; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D008315:Malondialdehyde; D004656:Enalapril; D002216:Captopril; D005978:Glutathione; D006909:Hydroxyproline