Nilotinib alleviates paraquat-induced hepatic and pulmonary injury in rats via the Nrf2/Nf-kB axis

Int Immunopharmacol. 2023 Sep 5;124(Pt A):110886. doi: 10.1016/j.intimp.2023.110886. Online ahead of print.ABSTRACTBACKGROUND: 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.METHODS: 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.RESULTS: 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 (...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Source Type: research