| First Author | Uehara T | Year | 2013 |
| Journal | Toxicol Appl Pharmacol | Volume | 266 |
| Issue | 2 | Pages | 224-32 |
| PubMed ID | 23200774 | Mgi Jnum | J:193336 |
| Mgi Id | MGI:5468202 | Doi | 10.1016/j.taap.2012.11.019 |
| Citation | Uehara T, et al. (2013) Acetaminophen-induced acute liver injury in HCV transgenic mice. Toxicol Appl Pharmacol 266(2):224-32 |
| abstractText | 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. |
