Pani P, Columbano A, Dessì S, Porcu M, Congiu L
Chem Biol Interact. 1976 Oct 2;15(2):107-16. doi: 10.1016/0009-2797(76)90156-3.
The effect of lead nitrate, an inhibitor of the hepatic drug-metabolizing enzyme system upon the acute, hepatotoxicity of dimethylnitrosamine (DMN) was studied. Lead pretreatment significantly prevented polysomal disaggregation induced by the nitrosamine. Cell necrosis, evaluated morphologically and by the release of serum glutamic-pyruvic transaminase (GPT), was also diminished. The metabolism of DMN in rats pretreated with lead nitrate was investigated by following its clearance from blood and by determining, in vitro the demethylation of the nitrosamine. Lead increased, although not significantly, the clearance of DMN from blood, but it lowered the activity of DMN-demethylase 24 h after its administration. Finally, lead lowered the lethal effects of DMN. The mechanism by which lead influenced DMN toxicity is discussed.
研究了肝药物代谢酶系统抑制剂硝酸铅对二甲基亚硝胺（DMN）急性肝毒性的影响。铅预处理显著预防了亚硝胺诱导的多核糖体解聚。通过形态学评估和血清谷丙转氨酶（GPT）释放评估的细胞坏死也有所减轻。通过跟踪硝酸铅预处理大鼠体内DMN从血液中的清除情况以及体外测定亚硝胺的去甲基化来研究DMN的代谢。铅虽未显著增加DMN从血液中的清除率，但在给药24小时后降低了DMN去甲基酶的活性。最后，铅降低了DMN的致死作用。讨论了铅影响DMN毒性的机制。
