Effect of diltiazem on acetaminophen and phalloidine hepatotoxicity.
The protective effect of diltiazem on acetaminophen and phalloidine hepatotoxicity has been studied in male CD-1 mice. Groups of 8 mice each received 0.9% NaCl or 6, 12, 18 and 24 mg/kg of diltiazem 20 minutes after 750 mg/kg of acetaminophen and were sacrificed 24 hours later to assess liver toxicity. Dosages of at least 12 mg/kg were required to prevent the increase in alanine transaminase (ALT) and only the 24 mg/kg hindered the appearance of histological lesions. ALT remained close to control values 48 hours after the administration of the 24 mg/kg dose of diltiazem. Diltiazem was less effective in preventing hepatotoxicity when administered 3 hours after acetaminophen. Diltiazem (24 mg/kg) reduced the increase in ALT induced by 1.1 mg/kg of phalloidine by 58% (4460 +/- 317 U/mL v.s. 1852 +/- 339 U/mL; p less than 0.05). It is concluded that high doses of diltiazem, administered early after the toxicant, prevent hepatic toxicity of acetaminophen but produce only a modest effect on phalloidine hepatotoxicity.
Kobusch
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Département de Pharmacologie, Faculté de Médecine, Université de Montréal, Québec.
du Souich
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D000082:Acetaminophen / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000410:Alanine Transaminase / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000037:antagonists & inhibitors*; D010590:Phalloidine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D013997:Time Factors
D009842:Oligopeptides; D010590:Phalloidine; D000082:Acetaminophen; D000410:Alanine Transaminase; D004110:Diltiazem; D002118:Calcium