Gender effects on the hepatic toxicity of cocaine and morphine in the guinea pig

B. Mets, A. Iso, K. Nakahara, L. Virag, K. Khan

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The effect of gender on the possible hepatotoxicity from morphine (100mg/kg), cocaine (30 mg/kg) or a combination of morphine (100mg/kg) and cocaine (30mg/kg) administered intraperitoneally were investigated in 24 male and 24 female guinea pigs. The time course of liver toxicity after single dose administration of test substances was also assessed by measuring plasma alanine aminotransferase (ALT) and isocitrate dehydrogenase (ICDH) levels over a period of 96 hours. ICDH values were measured in addition to the more usual ALT values to determine the suitability of using the former for assessing drug induced hepatotoxicity. Cocaine and morphine combined was shown to be hepatotoxic after single dose administration. Male guinea pigs were more susceptible than females as measured by higher plasma ALT and ICDH levels 4 to 24 hours after drug administration. In both sexes this combination provoked elevated liver enzyme activity different from control (saline) evident till 48 hours (ICDH) and 72 hours (ALT) after drug administration. No animals showed evidence of hepatotoxicity after 96 hours. Morphine alone resulted in higher levels of ALT (than control) in males, at 48 and 72 hours and in females, at 24 hours after administration. There was a significant correlation (r=0.74) between plasma ICDH and ALT levels. This study demonstrates that the combined administration of cocaine and morphine is hepatotoxic in the guinea pig and that the male is more susceptible. A theoretical explanation for this hepatotoxicity may be due to an additive effect of these drugs in depleting liver glutathione levels. Plasma ICDH can be considered a suitable indicator of drug induced hepatotoxicity but was no more sensitive than ALT.

Original languageEnglish (US)
Pages (from-to)93-104
Number of pages12
JournalResearch Communications in Substances of Abuse
Issue number1-2
StatePublished - Jan 1 1994

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)


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