chapter  5
28 Pages

Acetaminophen-Induced Hepatotoxicity

The majority of the mechanistic research studies have been conducted with mice, rats, and hamsters. Even among mice, toxicity varies with strain, age, and sex. Thus, DBA/2 mice are less susceptible than C57BU6 (19), young mice are less sensitive than mature mice (17, 20, 21), and female mice are more sensitive than male mice (22). By contrast, in Sprague-Dawley rats males are more sensitive than females (23), neonates are more resistant than young rats, and sensitivity to APAP is diminished in 2-year-old rats (24, 25). Rats also exhibit strain differences in susceptibility to APAP (26). Other experimental variables can affect APAP toxicity. These include the vehicle employed for APAP delivery (27, 28), both lighting and feeding schedules (29}, and dietary factors and nutritional status (3~37). Thus, it is important to be aware of these factors when designing and evaluating mechanistic studies and when comparing disparate results from apparently similar studies. It is also important to consider this when attempting to extrapolate mechanistic hypothesis from in vitro studies to toxicity in vivo.