Page 94 - Pharma News Letter - Vol2 Issue 1

Chapter V

Nilotinib Alleviates Paraquat-Induced Hepatic And Pulmonary
Injury In Rats Via The Nrf2/Nf-Kb Axis

International Immunopharmacology. 2023 Nov; 124(Pt A): 110886.
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Azza R Elkholy 1 , Ahmed R El-Sheakh 1, 2, 3 , Ghada M Suddek 1

1 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
2 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura National University, Gamasa,

Egypt.
3 Future studies and Risks management’ National Committee of Drugs, Academy of Scientific Research, Ministry of

Higher Education, Elsayeda Zeinab, Egypt.

Abstract

Background: 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 (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.
Significance: NIL suppressed PQ-induced inflammation, oxidative stress and apoptosis in liver
and lung tissues by modulating Nrf2/Nf-kB axis.

Reference:

https://doi.org/10.1016/j.intimp.2023.110886

94 Faculty of Pharmacy Newsletter