Acetaminophen hepatotoxicity in mice: Effect of age, frailty and exposure type.

摘要: Acetaminophen is a commonly used analgesic that can cause severe hepatotoxicity in overdose. Despite old age and frailty being associated with extensive long-term utilization of acetaminophen high prevalence adverse drug reactions, there limited information on the risks toxicity from frailty. This study aimed to assess changes risk mechanisms acute, chronic sub-acute exposure mice. Young male C57BL/6 mice were exposed either acute (300 mg/kg via oral gavage), (100 mg/kg/day diet for six weeks) or (250 mg/kg, t.i.d., three days) acetaminophen, saline control. Pre-dosing scored mouse clinical index, after dosing serum liver tissue collected assessment mechanisms. There no differences degree induced by subacute as assessed enzymes histology. Age-related pathways included increased GSH concentrations, NQO1 activity an pro- anti-inflammatory response age. Frailty-related negative correlation between index protein, albumin ALP concentrations some groups. In conclusion, although would be expected influence susceptibility toxicity, was overall increase