Tredger J M, Smith H M, Read R B, Portmann B, Williams R
Toxicology. 1985 Sep;36(4):341-52. doi: 10.1016/0300-483x(85)90035-6.
The influence of ethanol on paracetamol-induced liver damage was studied in mice and related to changes in microsomal monooxygenases and plasma paracetamol metabolites in the same group of animals. Paracetamol (400 mg/kg body wt, p.o.) was administered alone or simultaneously with ethanol (3 g/kg, p.o.) to mice fed either a chow diet or pretreated for 4 weeks with a liquid diet containing ethanol (20% of energy). Acute ethanol administration protected against paracetamol hepatotoxicity, but this protection was complete only in mice not fed ethanol previously. Acute ethanol administration also appeared to reduce paracetamol monooxygenation in vivo, but ethanol (50 mM) added to microsomal incubations in vitro had no significant effect on paracetamol activation and covalent binding. The chronic ingestion of ethanol in the diet increased paracetamol-related liver damage, but there appeared to be no induction of paracetamol monooxygenation in these animals. We are unable to confirm current concepts that the potentiation of paracetamol hepatotoxicity by chronic ethanol ingestion and its reduction by acute ethanol administration result solely from contrasting effects of ethanol on cytochrome P-450, and alternative explanations are proposed.
在小鼠中研究了乙醇对扑热息痛诱导的肝损伤的影响，并将其与同一组动物微粒体单加氧酶和血浆扑热息痛代谢物的变化相关联。将扑热息痛（400 mg/kg体重，口服）单独或与乙醇（3 g/kg，口服）同时给予喂食普通饲料的小鼠，或用含乙醇（能量的20%）的液体饲料预处理4周的小鼠。急性给予乙醇可预防扑热息痛的肝毒性，但这种保护仅在先前未喂食乙醇的小鼠中是完全的。急性给予乙醇似乎也会降低体内扑热息痛的单加氧作用，但在体外微粒体孵育中加入乙醇（50 mM）对扑热息痛的活化和共价结合没有显著影响。饮食中慢性摄入乙醇会增加与扑热息痛相关的肝损伤，但在这些动物中似乎没有诱导扑热息痛的单加氧作用。我们无法证实当前的观点，即慢性摄入乙醇增强扑热息痛的肝毒性以及急性给予乙醇降低其肝毒性完全是由于乙醇对细胞色素P-450的相反作用，并提出了其他解释。
