The protective effect of 7-hydroxycoumarin against cisplatin-induced liver injury is mediated via attenuation of oxidative stress and inflammation and upregulation of Nrf2/HO-1 pathway

Sami, Demiana H, Soliman, Ayman S, Khowailed, Akef A, Alruhaimi, Reem S, Hassanein, Emad HM, Kamel, Emadeldin M and Mahmoud, Ayman M (2023) The protective effect of 7-hydroxycoumarin against cisplatin-induced liver injury is mediated via attenuation of oxidative stress and inflammation and upregulation of Nrf2/HO-1 pathway. Environmental Science and Pollution Research, 30 (33). pp. 80181-80191. ISSN 0944-1344

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Official URL: https://doi.org/10.1007/s11356-023-27879-1

Abstract

Cisplatin (CIS) is an effective chemotherapy against different solid cancers. However, the adverse effects, including hepatotoxicity, limit its clinical use. 7-hydroxycoumarin (7-HC) possesses antioxidant and hepatoprotective activities, but its protective effect against CIS hepatotoxicity has not been investigated. This study evaluated the effect of 7-HC on liver injury, oxidative stress (OS), and inflammation provoked by CIS. Rats received 7-HC (25, 50, and 100 mg/kg) orally for 2 weeks followed by intraperitoneal injection of CIS (7 mg/kg) at day 15. CIS increased serum transaminases, alkaline phosphatase (ALP), and bilirubin and provoked tissue injury accompanied by elevated reactive oxygen species (ROS), malondialdehyde (MDA), and nitric oxide (NO). Liver nuclear factor (NF)-κB p65, inducible NO synthase (iNOS), pro-inflammatory cytokines, Bax, and caspase-3 were upregulated, and antioxidant defenses and Bcl-2 were decreased in CIS-treated rats, while 7-HC prevented liver injury and ameliorated OS, inflammatory and apoptosis markers. In addition, 7-HC enhanced nuclear factor erythroid 2–related factor 2 (Nrf2), and heme oxygenase (HO)-1 in CIS-administered rats and in silico studies revealed its binding affinity toward HO-1. In conclusion, 7-HC protected against CIS hepatotoxicity by mitigating OS and inflammatory response and modulating Nrf2/HO-1 pathway.

Item Type:	Article (Article)
Peer-reviewed:	Yes
Date Deposited:	09 Nov 2023 15:54
Publisher:	Springer (part of Springer Nature)
Additional Information:	This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use (https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms), but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1007/s11356-023-27879-1
Divisions:	Faculties > Science and Engineering
Subject terms:	Animals, Rats, Inflammation, Cisplatin, Umbelliferones, NF-kappa B, Antioxidants, Apoptosis, Up-Regulation, Oxidative Stress, NF-E2-Related Factor 2, Chemical and Drug Induced Liver Injury, Chronic, Cisplatin, Hepatotoxicity, Inflammation, Oxidative stress, Umbelliferone, Rats, Animals, Antioxidants, Cisplatin, NF-E2-Related Factor 2, Up-Regulation, Chemical and Drug Induced Liver Injury, Chronic, Oxidative Stress, Inflammation, NF-kappa B, Umbelliferones, Apoptosis, 03 Chemical Sciences, 05 Environmental Sciences, 06 Biological Sciences, Environmental Sciences
Data Access Statement:	The manuscript and supplementary material contain all data supporting the reported results.
URI:	https://e-space.mmu.ac.uk/id/eprint/633040
DOI:	https://doi.org/10.1007/s11356-023-27879-1
ISSN	0944-1344
e-ISSN	1614-7499

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