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tenuior提取物对毒死蜱诱导的大鼠肝肺毒性的保护作用:亚慢性研究中的作用机制探讨

Protective effects of Ziziphora tenuior extract against chlorpyrifos induced liver and lung toxicity in rat: Mechanistic approaches in subchronic study.

作者信息

Yazdinezhad Alireza, Abbasian Meysam, Hojjat Hosseini Seyed, Naserzadeh Parvaneh, Agh-Atabay Abdol-Hakim, Hosseini Mir-Jamal

机构信息

Department of Pharmacognosy, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.

Zanjan Applied Pharmacology Research Center, Zanjan University of Medical sciences, Zanjan, Iran.

出版信息

Environ Toxicol. 2017 Sep;32(9):2191-2202. doi: 10.1002/tox.22432. Epub 2017 Jun 1.

Abstract

Chlorpyrifos (CPF) is one of the most widely used organophosphorus, which has spurred renewed interest. This study was conducted to investigate the protective effect of ziziphora tenuior extract against CPF-induced liver and lung toxicity. This study conducted 8-week rat sub-chronic toxicity study and then the effect of ziziphora tenuior extract in 3 different doses (40, 80, 160 mg/kg) was determined. We administrated maximum tolerated dose of CPF (6.75 mg/kg) by gavage for 8 weeks (5 times in week) to male rats. Rats were sacrificed 24 h after last dose and the biochemical analysis, which confirms involvement of oxidative stress in the pathogenesis of CPF toxicity in liver including increased in lipid peroxidation, protein carbonyl content, and ROS formation, glutathione depletion, decreased of antioxidant effect via frap oxidation and cytochrome c expulsion. In addition, pathological lesions confirm the dysfunction of the organs (liver and lung). In addition, using of ziziphora extract as an antioxidant is resulted in amelioration of oxidative stress marker in liver and lung damage. In conclusion, the current study revealed that CPF toxicity is related to oxidative stress and induction of cell death signaling and cotreatment with ziziphora extract is recommended in the routine therapy for the protection against CPF induced liver and lung tissue damage.

摘要

毒死蜱(CPF)是使用最广泛的有机磷之一,这引发了新的关注。本研究旨在探讨细叶紫苏提取物对CPF诱导的肝脏和肺部毒性的保护作用。本研究进行了为期8周的大鼠亚慢性毒性研究,然后测定了3种不同剂量(40、80、160mg/kg)细叶紫苏提取物的效果。我们通过灌胃给雄性大鼠施用最大耐受剂量的CPF(6.75mg/kg),持续8周(每周5次)。在最后一次给药后24小时处死大鼠,并进行生化分析,该分析证实氧化应激参与了CPF诱导的肝脏毒性发病机制,包括脂质过氧化增加、蛋白质羰基含量增加、活性氧生成、谷胱甘肽耗竭、通过铁还原抗氧化能力氧化和细胞色素c排出导致抗氧化作用降低。此外,病理损伤证实了器官(肝脏和肺)的功能障碍。此外,使用细叶紫苏提取物作为抗氧化剂可改善肝脏和肺部损伤中的氧化应激标志物。总之,当前研究表明CPF毒性与氧化应激和细胞死亡信号诱导有关,建议在常规治疗中联合使用细叶紫苏提取物以预防CPF诱导的肝脏和肺组织损伤。

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