Diazinon (DZN) is a broad-spectrum insecticide extensively used to control pests in crops and animals. Several investigators demonstrated that DZN produced tissue toxicity especially to the liver. In addition, the mitochondrion was implicated in DZN-induced toxicity, but the precise role of this organelle remains to be determined. The aim of this study was thus to examine the effects of DZN (50 to 150 μM) on the bioenergetics and mitochondrial permeability transition (MPT) associated processes in isolated rat liver mitochondria. DZN inhibited state-3 respiration in mitochondria energized with glutamate plus malate, substrates of complex I, and succinate, substrate of complex II of the respiratory chain and decreased the mitochondrial membrane potential resulting in inhibition of ATP synthesis. MPT was estimated by the extent of mitochondrial swelling, in the presence of 10 µM Ca²⁺. DZN elicited MPT in a concentration-dependent manner, via a mechanism sensitive to cyclosporine A, EGTA, ruthenium red and N-ethylmaleimide, which was associated with mitochondrial Ca²⁺ efflux and cytochrome c release. DZN did not result in hydrogen peroxide accumulation or glutathione oxidation, but this insecticide oxidized endogenous NAD(P)H and protein thiol groups. Data suggest the involvement of mitochondria, via apoptosis, in the hepatic cytotoxicity attributed to DZN.

Diazinon（DZN）是一种广谱杀虫剂，广泛用于控制农作物和动物中的害虫。几位研究人员证明DZN尤其对肝脏产生组织毒性。此外，线粒体与DZN诱导的毒性有关，但该细胞器的确切作用尚待确定。因此，本研究的目的是检验DZN（50至150μM）对离体大鼠肝线粒体中生物能学和线粒体通透性转变（MPT）相关过程的影响。DZN抑制了由谷氨酸加苹果酸，复合物I的底物和琥珀酸，呼吸链的复合物II的底物激发的线粒体的状态3呼吸，并降低了线粒体膜电位，从而抑制了ATP的合成。²⁺。DZN通过对环孢菌素A，EGTA，钌红和N-乙基马来酰亚胺敏感的机制以浓度依赖的方式引起MPT，这与线粒体Ca ²⁺外排和细胞色素c释放有关。DZN不会导致过氧化氢的积累或谷胱甘肽氧化，但这种杀虫剂会氧化内源性NAD（P）H和蛋白质硫醇基团。数据表明线粒体通过细胞凋亡参与归因于DZN的肝细胞毒性作用。