Cadmium-induced lung injury is associated with oxidative stress, apoptosis, and altered SIRT1 and Nrf2/HO-1 signaling; protective role of the melatonin agonist agomelatine

Alruhaimi, Reem S, Hassanein, Emad H M, Bin-Jumah, May N and Mahmoud, Ayman M ORCID: https://orcid.org/0000-0003-0279-6500 (2024) Cadmium-induced lung injury is associated with oxidative stress, apoptosis, and altered SIRT1 and Nrf2/HO-1 signaling; protective role of the melatonin agonist agomelatine. Naunyn-Schmiedeberg's Archives of Pharmacology, 397 (4). pp. 2335-2345. ISSN 0028-1298

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Official URL: http://dx.doi.org/10.1007/s00210-023-02754-5

Abstract

Cadmium (Cd) is a hazardous heavy metal extensively employed in manufacturing polyvinyl chloride, batteries, and other industries. Acute lung injury has been directly connected to Cd exposure. Agomelatine (AGM), a melatonin analog, is a drug licensed for treating severe depression. This study evaluated the effect of AGM against Cd-induced lung injury in rats. AGM was administered in a dose of 25 mg/kg/day orally, while cadmium chloride (CdCl2) was injected intraperitoneally in a dose of 1.2 mg/kg to induce lung injury. Pre-treatment with AGM remarkably ameliorated Cd-induced lung histopathological abrasions. AGM decreased reactive oxygen species (ROS) production, lipid peroxidation, suppressed NDAPH oxidase, and boosted the antioxidants. AGM increased Nrf2, GCLC, HO-1, and TNXRD1 mRNA, as well as HO-1 activity and downregulated Keap1. AGM downregulated Bax and caspase-3 and upregulated Bcl-2, SIRT1, and FOXO3 expression levels in the lung. In conclusion, AGM has a protective effect against Cd-induced lung injury via its antioxidant and anti-apoptotic effects mediated via regulating Nrf2/HO-1 and SIRT1/FOXO3 signaling.

Item Type:	Article (Article)
Peer-reviewed:	Yes
Date Deposited:	15 May 2024 14:44
Publisher:	Springer
Additional Information:	This version of the article has been accepted for publication, after peer review 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/s00210-023-02754-5
Divisions:	Faculties > Science and Engineering
Subject terms:	Animals, Rats, Cadmium, Melatonin, Antioxidants, Apoptosis, Oxidative Stress, NF-E2-Related Factor 2, Lung Injury, Sirtuin 1, Kelch-Like ECH-Associated Protein 1, Agomelatine, Cadmium, Oxidative stress, Rats, Animals, Cadmium, NF-E2-Related Factor 2, Melatonin, Kelch-Like ECH-Associated Protein 1, Lung Injury, Sirtuin 1, Oxidative Stress, Antioxidants, Apoptosis, 1115 Pharmacology and Pharmaceutical Sciences, 1116 Medical Physiology, Pharmacology & Pharmacy
Data Access Statement:	The authors confirm that the data supporting the findings of this study are available within the article.
URI:	https://e-space.mmu.ac.uk/id/eprint/634636
DOI:	https://doi.org/10.1007/s00210-023-02754-5
ISSN	0028-1298
e-ISSN	1432-1912

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