Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Pharmacology and Toxicology Department, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Students' Research Committee, Tabriz University of Medical Science, Tabriz, Iran.
J Biochem Mol Toxicol. 2013 Oct;27(10):457-62. doi: 10.1002/jbt.21509. Epub 2013 Sep 10.
It has been reported that the bioactive intermediate metabolites of trazodone might cause hepatotoxicity. This study was designed to investigate the exact mechanism of hepatocellular injury induced by trazodone as well as the protective effects of taurine and/or melatonin against this toxicity. Freshly isolated rat hepatocytes were used. Trazodone was cytotoxic and caused cell death with LC50 of 300 µm within 2 h. Trazodone caused an increase in reactive oxygen species (ROS) formation, malondialdehyde accumulation, depletion of intracellular reduced glutathione (GSH), rise of oxidized glutathione disulfide (GSSG), and a decrease in mitochondrial membrane potential, which confirms the role of oxidative stress in trazodone-induced cytotoxicity. Preincubation of hepatocytes with taurine prevented ROS formation, lipid peroxidation, depletion of intracellular reduced GSH, and increase of oxidized GSSG. Taurine could also protect mitochondria against trazodone-induced toxicity. Administration of melatonin reduced the toxic effects of trazodone in isolated rat hepatocytes.
据报道，曲唑酮的生物活性中间代谢产物可能导致肝毒性。本研究旨在探讨曲唑酮诱导肝细胞损伤的确切机制，以及牛磺酸和/或褪黑素对这种毒性的保护作用。使用新鲜分离的大鼠肝细胞。曲唑酮具有细胞毒性，在 2 小时内 LC50 为 300 µm 时导致细胞死亡。曲唑酮导致活性氧（ROS）形成增加，丙二醛积累，细胞内还原型谷胱甘肽（GSH）耗竭，氧化型谷胱甘肽二硫化物（GSSG）升高，线粒体膜电位降低，这证实了氧化应激在曲唑酮诱导的细胞毒性中的作用。用牛磺酸孵育肝细胞可防止 ROS 形成、脂质过氧化、细胞内还原型 GSH 耗竭和氧化型 GSSG 增加。牛磺酸还可以保护线粒体免受曲唑酮诱导的毒性。褪黑素的给药可降低曲唑酮对离体大鼠肝细胞的毒性作用。
