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ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1572095
This article is part of the Research TopicNovel Molecular Targets in Cancer TherapyView all 27 articles
Impact of thymoquinone on Nrf2/HO-1 and MAPK/NFkBNF-κB axis in mitigating 5-Flurouracil induced acute kidney injury in vivo
Provisionally accepted- College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia
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Background: Chemotherapy induced organ toxicities is the most frequent toxic manifestation of 5fluorouracil (5-FUu) action in cancer patients. Hence, new approaches are required to deter chemotherapy induced kidney toxicity. Thymoquinone (TQ) is one of the constituents of plant nigella sativa belonging to family Renunculaceae., It is found to be anti-apoptotic, antioxidant, anti-microbial, anti-inflammatory and mitigate renal damage. Thus, this work was designed this work to evaluate the effect of TQ in averting nephrotoxicity induced by 5-FU treatment.Method: Male albino wistar rats were grouped and given saline, 5-FU group (150 mg/kg), 5-FU+TQ (50 mg/kg) and 5-FU+TQ (100 mg/kg) to group I, II, III and IV respectively. Rats were sacrificed on 21 st day and biochemical, histological, serological and molecular estimations were done with kidney tissues and blood.Results: 5-FU caused kidney injury as demonstrated by variations in kidney function markers (BUN, Cr, LDH, Kim-1), lipid peroxidation (LPO), ROS generation, histology and diminution of antioxidant guard machinery (GSH, GR, GPx and CAT) demonstrating kidney damage. Additionally, 5-FU instigated crosstalk between Nrf2 and NFkBNF-κB /p38MAPK axis by upregulating p-p38, p-JNK, p-ERK1/2, p-NFkBNF-κB , TNF-α, IL-1β, TGF-β, IL-6 and downregulating Nrf2, HO-1 significantly resulting in kidney injury. PTQ pre, post and co-treatment of TQ alleviated kidney injury by replenishing the antioxidant reservoirs, reducing serum toxicity, ROS generation, lipid peroxidation, downregulation of p38 MAPK/NFkBNF-κB axis/pathway proteins, upregulation of Nrf2, HO-1 boosting the anti-oxidant axis and restoration of kidney architecture.Henceforth, based on the results obtained in the present study, TQ is found to be a beneficial agent which could be used in adjuvant therapy for the prevention of nephrotoxicity caused by 5-FU.
Keywords: Thymoquinone, p38MAPK, NF-kB, Inflammation, Oxidative Stress, Redox signalling, Nrf2/ HO-1 signaling pathway
Received: 06 Feb 2025; Accepted: 15 Apr 2025.
Copyright: © 2025 Rashid. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Summya Rashid, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia
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