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KMID : 0617219980090010101
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Duksung Bulletin Phamaceutical Sciences
1998 Volume.9 No. 1 p.101 ~ p.109
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Effect and Histopathologic Examination of Calcium Channel Blocker on Carbon Tetrachloride-induced Hepatotoxicity in Rats
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Abstract
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Carbon tetrachloride (CCl_4) induces the hepatotoxicity due to the reactive free radicals generated by cytochrome P-450 (CYP-450) enzyme, which result in destabilization of cellular membrane. Diltiazem, a calcium channel blocking agent, has been known to suppress the CYP-450 enzyme activities. To study the effect of diltiazem in CCl_4-treated rats, we measured the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutathione S-transferase (GST), contents of bilirubin, albumin, total protein, cholesterol, triglyceride, blood urea nitrogen, creatinine malondialdehyde and calcium. Also we conducted liver histopathologic examinations. Diltiazem, when administered 1 hour prior to CCl_4 treatment, significantly reduced the activities of ALT and AST, the contents of microsomal malondialdehyde and calcium in liver and microsome as compared with those of CCl_4-treated rats. In addition, histopathologic examination showed that diltiazem prevented the development of centrilobular necrosis induced by CCl_4 in liver tissue. Our results suggested that diltiazem could inhibit the formation of free radicals and the influx of calcium. Therefore diltiazem may be applied to suppress the liver damage caused by CCl_4.
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