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Journal of Pharmacology and Toxicology

Year: 2007 | Volume: 2 | Issue: 7 | Page No.: 610-620
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Authors

Omar M.E. Abdel Salam

Nabila S. Hassan

Ayman R. Baiuomy

Sawsan H. Karam

Keywords

The present study compared the effect of the calcium channel blockers amlodipine and diltiazem with the ACE inhibitor enalapril on CCl4-induced acute hepatic injury in rats. Amlodipine (0.9 or 1.8 mg kg-1), diltiazem (10.8 or 21.6 mg kg-1) and enalapril (0.9 or 1.8 mg kg-1) were administered per os daily for 7 days, then acute hepatic injury was induced by treating rats using a gavage with a single dose of CCl4-olive oil (1:1, 0.2 mL/100 g). Drug administration continued after CCl4 and the treated animals were killed on day 3 after CCl4 administration. Results indicated that whereas a reduction in serum enzyme levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) was obtained with amlodipine and enalapril, no protective effect was observed for diltiazem in this model of hepatic injury. Thus, compared with the CCl4 control group, serum ALT decreased by 56.2-61.4 and AST by 16-25.1%, after the administration of amlodipine at 0.9 and 1.8 mg kg-1, respectively. Serum ALP was significantly reduced by 40% by 1.8 mg kg-1 amlodipine. Enalapril administered at 0.9 and 1.8 mg kg-1 significantly decreased ALT by 22.8-61.4%, while AST and ALP were significantly reduced by 37.3 and 54.5%, respectively by 1.8 mg kg-1 enalapril. In contrast, diltiazem administered at 20.4 mg kg-1 increased ALT and AST levels by 43 and 16%, respectively. Histologic examination of haematoxylin and eosin stained sections from the livers of rats treated with CCl4 and amlodipine showed prominent improvement in liver architecture, a decrease in inflammatory cells and necrotic area. Electron microscopic examination of hepatocytes of CCl4-treated rat showed disorganization of the cytoplasmic structure and degeneration of cytoplasmic organelles. Electron microscopy of hepatocytes from the rats treated with CCl4 + amlodipine revealed healthy cytoplasmic content with healthy nuclei and normal mitochondria. Similar findings were observed after enalapril treatment. In contrast, intensive necrosis and degeneration was seen in livers of rats treated with diltiazem. On electron microscopy in most of hepatocytes, the cytoplasm became lytic with distorted mitochondrial cristae and highly dilated endoplasmic reticulum. Thus two calcium channel blockers behaved differently as regards to hepatic injury in the model of CCl4-induced hepatic injury. It is suggested that profound haemodynamic effects of diltiazem which undergoes extensive hepatic metabolism and the resultant decrease in hepatic blood flow account for the observed effect of the drug.
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