POTENTIATION OF ACETAMINOPHEN HEPATOTOXICITY AND MORTALITY BY DOXAPRAM IN MICE

Whether a single dose of doxapram (DOP) can modulate the acute toxicit y and the hepatotoxicity induced by acetaminphen (AA) was examined. Pr etreatment with DOP (40 mg/kg, i.p.) 30 min prior to the administratio n of AA dose-dependently potentiated the lethality of AA in both nativ e mice and mice fasted for 18 h, and the potentiating activity was gre ater in fasted mice than in native mice. The hepatotoxicity of AA was assessed by plasma transaminases activity (glutamyl oxaloacetic transa minase, GOT; glutamyl pyruvic transaminase, GPT) and the amount of pla sma lipid peroxides at 6, 12, 18, 24, 36 and 48 h after the administra tion of AA and histopathological examination of liver sections at 24 h after the administration of AA. DOP (40 mg/kg, i.p.) did not increase the plasma transaminase activity or the lipid peroxides level signifi cantly, whereas AA administration to DOP-treated animals produced earl ier maximal elevation of transaminase and lipid peroxide values compar ed to AA alone. These findings indicate that mortality and hepatotoxic ity of AA is potentiated by DOP in mice.