Coenzyme Q10 mitigates cadmium cardiotoxicity by downregulating NF-κB/NLRP3 inflammasome axis and attenuating oxidative stress in mice.

Autor: Antar SA; Center for Vascular and Heart Research, Fralin Biomedical Research Institute, Virginia Tech, Roanoke, VA 24016, USA; Department of Pharmacology, Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, Egypt., Abdo W; Department of Pathology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33511, Egypt., Helal AI; Department of Histology and Cell Biology, Faculty of Medicine, Kafrelsheikh University, Kafrelsheikh 33511, Egypt., Abduh MS; Immune Responses in Different Diseases Research Group, Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia., Hakami ZH; Medical Laboratory Technology Department, College of Applied Medical Sciences, Jazan University, Jazan 82817, Saudi Arabia., Germoush MO; Biology Department, College of Science, Jouf University, Sakakah 72388, Saudi Arabia., Alsulimani A; Medical Laboratory Technology Department, College of Applied Medical Sciences, Jazan University, Jazan 82817, Saudi Arabia., Al-Noshokaty TM; Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt., El-Dessouki AM; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ahram Canadian University, 6th of October, Giza 12566, Egypt., ElMahdy MK; Department of Pharmacology, Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, Egypt., Elgebaly HA; Biology Department, College of Science, Jouf University, Sakakah 72388, Saudi Arabia., Al-Karmalawy AA; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, Egypt; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, 6(th) of October, Giza 12566, Egypt., Mahmoud AM; Department of Life Sciences, Faculty of Science & Engineering, Manchester Metropolitan University, Manchester M1 5GD, UK; Molecular Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62514, Egypt. Electronic address: a.mahmoud@mmu.ac.uk.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2024 Jul 01; Vol. 348, pp. 122688. Date of Electronic Publication: 2024 May 04.
DOI: 10.1016/j.lfs.2024.122688
Abstrakt: Coenzyme Q10 (CoQ10) occurs naturally in the body and possesses antioxidant and cardioprotective effects. Cardiotoxicity has emerged as a serious effect of the exposure to cadmium (Cd). This study investigated the curative potential of CoQ10 on Cd cardiotoxicity in mice, emphasizing the involvement of oxidative stress (OS) and NF-κB/NLRP3 inflammasome axis. Mice received a single intraperitoneal dose of CdCl 2 (6.5 mg/kg) and a week after, CoQ10 (100 mg/kg) was supplemented daily for 14 days. Mice that received Cd exhibited cardiac injury manifested by the elevated circulating cardiac troponin T (cTnT), CK-MB, LDH and AST. The histopathological and ultrastructural investigations supported the biochemical findings of cardiotoxicity in Cd-exposed mice. Cd administration increased cardiac MDA, NO and 8-oxodG while suppressed GSH and antioxidant enzymes. CoQ10 decreased serum CK-MB, LDH, AST and cTnT, ameliorated histopathological and ultrastructural changes in the heart of mice, decreased cardiac MDA, NO, and 8-OHdG and improved antioxidants. CoQ10 downregulated NF-κB p65, NLRP3 inflammasome, IL-1β, MCP-1, JNK1, and TGF-β in the heart of Cd-administered mice. Moreover, in silico molecular docking revealed the binding potential between CoQ10 and NF-κB, ASC1 PYD domain, NLRP3 PYD domain, MCP-1, and JNK. In conclusion, CoQ10 ameliorated Cd cardiotoxicity by preventing OS and inflammation and modulating NF-κB/NLRP3 inflammasome axis in mice. Therefore, CoQ10 exhibits potent therapeutic benefits in safeguarding cardiac tissue from the harmful consequences of exposure to Cd.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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