Hepatitis C virus structural proteins can exacerbate or ameliorate acetaminophen-induced liver injury in mice

Archives of Toxicology
Anup RamachandranHartmut Jaeschke

Abstract

Chronic hepatitis C virus (HCV) infection predisposes patients to develop liver failure after acetaminophen (APAP) overdose. Mechanisms involved in this were explored using transgenic mice expressing the HCV structural proteins core, E1 and E2. Treatment of C57BL/6J mice with 200 mg/kg body weight APAP resulted in significant liver injury at 6 h as indicated by elevated ALT levels, focal centrilobular necrosis and nuclear DNA fragmentation. HCV transgenic mice showed a variable response, with approximately half the animals showing exacerbation of all parameters of liver injury, while the other half was protected. HCV transgenic mice with higher liver injury had lower liver glutathione levels, elevated mitochondrial oxidative stress and enhanced release of apoptosis-inducing factor (AIF) from the mitochondria. This was accompanied by induction of a higher ER stress response and induction of autophagy. Transgenic animals showing protection against liver injury had a robust recovery of liver glutathione content at 6 h when compared to wild-type animals, accompanied by reduction in mitochondrial oxidative stress and AIF release. This was accompanied by an elevation in glutathione S-transferase mRNA levels and activity, which sugges...Continue Reading

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Citations

Oct 18, 2018·Journal of Pineal Research·Jose A BogaAna Coto-Montes
Jun 13, 2020·Archives of Toxicology·Qiuhua TanZhengquan Su
Oct 22, 2017·Gene Expression·Anup Ramachandran, Hartmut Jaeschke

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