Analysis of the molecular mechanism of hepatic GSH decrease during drug induced liver injury.

已知最小剂量的脂多糖(LPS)预处理会增加动物对药物性肝损伤的敏感性，否则几乎不受单独药物的影响。除了先前提出的由内毒素预处理产生的炎性细胞因子外，我们已经证明，在该内毒素模型中，肝脏GSH降低是协同加重DILI的一个重要因素。此外，脂多糖处理后肝脏GSH降低的机制存在种属差异，大鼠GSH基侧外流增加，而小鼠GSH代谢途径有所参与。

It is known that pretreatment of minimum amount of lipopolysaccharide(LPS) increases the animals to drug-induced liver injury, otherwise they are hardly affected by drug alone. In addition to previously proposed inflammatory cytokines produced by LPS pre-treatment, we have demonstrated that hepatic GSH decrease is an important factor cooperatively aggravates DILI in this LPS model. Moreover, species difference of the mechanism of hepatic GSH decrease after LPS treatment was emerged ; basolateral efflux of GSH was increased in rat, while metabolic pathway was somehow involved in mouse.