Acetaminophen-induced acute liver injury in HCV transgenic mice. Academic Article uri icon

abstract

  • The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility.

published proceedings

  • Toxicol Appl Pharmacol

author list (cited authors)

  • Uehara, T., Kosyk, O., Jeannot, E., Bradford, B. U., Tech, K., Macdonald, J. M., ... Rusyn, I.

citation count

  • 8

complete list of authors

  • Uehara, Takeki||Kosyk, Oksana||Jeannot, Emmanuelle||Bradford, Blair U||Tech, Katherine||Macdonald, Jeffrey M||Boorman, Gary A||Chatterjee, Saurabh||Mason, Ronald P||Melnyk, Stepan B||Tryndyak, Volodymyr P||Pogribny, Igor P||Rusyn, Ivan

publication date

  • January 2013