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pp.258-267
The acetaminophen (APAP), an antipyretic and analgesic agent, induces the hepatotoxicity by increasing influx of calcium and destabilizing the cellular membrane which can be caused by N-acetyl p-benzoquinoneimine generated by cytochrome P-450 (CYP-450) when it is overdosed. Diltiazem (DIL), a calcium channel blocking agent, has been known to suppress the CYP-450 activities. To study the effect of DIL in APAP treated rats, the serum biotransformational enzyme analyses and the liver histopathologic examination were conducted on the rats which had been administered DIL at 3, 6, 9 and 12 hours after the 3,000 mg/kg of APAP administration. Following a single dose of DIL administered 12 hours after APAP administration, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, malondialdehyde and calcium contents of liver and microsome were significantly reduced. Glutathione S-transferase (GST) activity was significantly increased. Histopathologic studies showed that DIL had prevented the development of centrilobular necrosis induced by APAP in liver tissue. Our results suggested that diltiazem could inhibit the formation of free radical and the influx of calcium and could increase GST activity. Therefore, diltiazem can be administered at the time of 12 hours after overdosed APAP to diminish the liver damage.
