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

Antar, SA, Abdo, W, Helal, AI, Abduh, MS, Hakami, ZH, Germoush, MO, Alsulimani, A, AL-Noshokaty, TM, El-Dessouki, AM, ElMahdy, MK, Elgebaly, HA, Al-Karmalawy, AA and Mahmoud, AM (2024) Coenzyme Q10 mitigates cadmium cardiotoxicity by downregulating NF-κB/NLRP3 inflammasome axis and attenuating oxidative stress in mice. Life Sciences, 348. 122688. ISSN 0024-3205

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Abstract

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 CdCl2 (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.