双氯灭痛对小鼠肝脏氧化应激的诱导作用

Induction of oxidative damage by diclofenac in the mouse liver

目的 研究双氯灭痛 (diclofenac)单次给药不同剂量和给药后不同时间对小鼠肝脏氧化应激的诱导作用。方法 成年雄性ICR小鼠单次灌胃给药 (5 0、10 0、2 0 0和 3 0 0mg kg) ,观察肝脏脂质过氧化、谷胱甘肽 (GSH)和金属硫蛋白(MT)含量等指标的变化。结果 给药后的小鼠肝脏脂质过氧化产物丙二醛 (MDA)含量显著升高 ,呈明显的剂量 -效应关系和时间 -效应关系 ,3 0 0mg kg组的最高值为对照组的 1 9倍。肝脏还原型谷胱甘肽 (GSH)含量随染毒剂量加大和时间延长明显下降 ,最低值为对照组的 3 4%。给药后肝脏MT含量明显升高 ,5 0mg kg组的最高值达对照组的 3 9倍。相关分析显示MDA与MT含量呈正相关。结论 双氯灭痛能诱导小鼠肝脏发生氧化应激损伤。MT诱导可能是对抗氧化损伤的保护机制之一。

Objective To evaluate oxidative stress involving metallothionein (MT) induced by different doses of diclofenac in mouse liver.Methods Adult male ICR mice were administered different doses of diclofenac (50,100,200,300 mg/kg) by oral gavage.Lipid peroxidation, glutathione (GSH) and MT contents in liver were determined.Results\ Malondialdehyde (MDA) in liver significantely increased in the dose\|dependent manner and time\|dependent manner.The highest of group 300 mg/kg was 1.9 fold compared to the control.GSH in liver rapidly decreased,the lowest was only 34% of he control.Moreover,GSH also showed preferable dose\|effect and time\|effect relationship.Liver MT content was markedly increased,the highest of group 50 mg/kg was 3.9 fold compared to the control.The MDA level had a negative correlation with the level of MT.Discussion\ Diclofenac can induce oxidative stress in mouse liver and MT may be one of the mechanisms that can protect this injury.