百草枯（PQ，1,1'-二甲基-4,4'-联吡啶二氯化物）是一种在农业广泛使用的高毒性季铵类除草剂。它主要通过生成超氧阴离子的氧化还原循环作用对生物体产生毒性影响，导致细胞氧化还原状态失衡，进而引发氧化损伤和细胞死亡。本研究旨在评估尼洛替尼（NIL）对PQ诱导的大鼠肝肺毒性的保护作用。雄性Wistar大鼠随机分为四组，分别为对照组，PQ组（15mg/kg），PQ加NIL组（5mg/kg），以及PQ加NIL组（10mg/kg）。NIL（5和10mg/kg/d）通过口服注射器连续给予五天，随后于第六天通过腹腔单次给予PQ（15mg/kg）。NIL预处理缓解了肝脏和肺组织的组织学损伤，并改善了肝功能生化标志物，显著（p < 0.05）降低了ALT，AST，ALP，Y-GT和总胆红素的血清水平，同时增加了白蛋白水平。与此同时，NIL显著（p < 0.05）降低了肝脏和肺组织中的氧化应激标志物通过降低丙二醛（MDA）的含量和提高谷胱甘肽（GSH）的含量。此外，NIL显著（p < 0.05）通过降低肝脏和肺组织中的肿瘤坏死因子α（TNF-α）和核转录因子κB（NF-KB/p65）的含量降低了炎症水平。尼洛替尼还通过降低半胱氨酸天冬氨酸特异性蛋白酶3（caspase-3）来下调细胞凋亡。此外，它在肝脏和肺组织中上调了核因子红细胞2相关因子2（Nrf2）和微管相关蛋白1A/1B-轻链3 II（LC3II）的表达。NIL通过调节Nrf2/Nf-kB通路抑制了PQ诱导的肝肺组织炎症，氧化应激和细胞凋亡。版权所有©2023年Elsevier B.V.保留所有权利。

Paraquat (PQ, 1,1'-dimethyl-4-4'-bipyridinium dichloride) is a highly toxic quaternary ammonium herbicide widely used in agriculture. It exerts its toxic effects mainly as a result of its redox cycle via the production of superoxide anions in organisms, leading to an imbalance in the redox state of the cell causing oxidative damage and finally cell death. The aim of this study was to estimate the beneficial protective role of nilotinib (NIL) on PQ-induced hepatic and pulmonary toxicity in rats.Male wistar rats were randomly divided into four groups, namely control, PQ (15 mg/kg), PQ plus NIL (5 mg/kg) and PQ plus NIL (10 mg/kg). NIL (5 and 10 mg/kg/day) was taken by oral syringe for five days followed by a single intra-peritoneal administration of PQ (15 mg/kg) on sixth day.Pretreatment with NIL relieved the histological damage in liver and lung tissues and improved hepatic biochemical markers. It significantly (p < 0.05) reduced serum levels of ALT, AST, ALP, Y-GT and total bilirubin while increased that of albumin. Meanwhile, NIL significantly (p < 0.05) reduced oxidative stress markers via reduction of malondialdhyde (MDA) and elevation of glutathione (GSH) contents in liver and lung tissues. In addition, it significantly (p < 0.05) decreased the inflammation by reducing hepatic and pulmonary tumor necrosis factor alpha (TNF-α) and nuclear transcription factor kappa B (NF-KB/p65) contents. Nilotinib also down-regulated apoptosis by reducing cysteinyl aspartate-specific proteinase-3 (caspase-3). Furthermore, it upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and microtubule-associated protein 1A/1B-light chain 3 II (LC3II) in liver and lung tissues.NIL suppressed PQ-induced inflammation, oxidative stress and apoptosis in liver and lung tissues by modulating Nrf2/Nf-kB axis.Copyright © 2023 Elsevier B.V. All rights reserved.