Increased resistance to acetaminophen-induced hepatotoxicity in retrovirus-infected mice

Biopharmaceutics & Drug Disposition
H H ChowR R Watson

Abstract

In this research we examined the influence of chronic retrovirus infection on the hepatic metabolism of a model substrate, acetaminophen (APAP), and its induced liver injury in mice inoculated with LP-BM5 murine leukemia viruses. Female C57BL/6 mice at 15-17 wks after LP-BM5 retrovirus inoculation and age-matched control animals were used in the studies. APAP treatment (300 mg kg-1, p.o.) resulted in moderate to severe centrilobular necrosis in control animals, with the necrotic area accounting for 40-60% of the total area. In contrast, the APAP-treated (300 mg kg-1, p.o.) infected animals exhibited mild zonal necrosis with the necrotic area accounting for 1-6% of the total area. In the same study, a statistically significant higher percentage of APAP glucuronide and a lower percentage of unchanged APAP were recovered from the urine of the LP-BM5-inoculated animals than from that of controls. No statistically significant differences between infected and uninfected animals in the urinary recovery of APAP sulfate, APAP cysteine, or APAP mercapturate were observed. The formation of APAP metabolites and APAP-associated biochemical changes were also determined from liver slice preparation to avoid in vivo complicating factors. Consi...Continue Reading

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