Coenzyme Q10 and its liposomal form prevent copper cardiotoxicity by attenuating oxidative stress, TLR-4/NF-κB signaling and necroptosis in rats

CoQ10 and L-CoQ10 prevent Cu cardiotoxicity in rats

Abstract

Copper (Cu) is an essential element involved in numerous biochemical, metabolic and cellular processes. Excessive exposure to the pesticide copper sulfate (CuSO₄) was associated with toxic effects. This study aims to evaluate the efficacy of Coenzyme Q10 (CoQ10) and its liposomal form (L-CoQ10) against myocardial injury induced by CuSO₄, pinpointing the involvement of redox imbalance, TLR-4/NF-κB signaling and apoptosis. Cardiac injury in rats was induced by daily oral doses of CuSO₄ for 7 days, the rats were treated orally with either CoQ10 or L-CoQ10 concurrently with CuSO₄ for 7 days. Elevated serum cTnI, CK-MB and LDH were observed in CuSO₄-intoxicated animals. Additionally, cellular antioxidant biomarkers were decreased and the expression levels of cardiac MDA, TLR-4, NF-κB, IL-6, IL-1β, and TNF-α were upregulated. CoQ10 and L-CoQ10 prevented myocardial injury and decreased the levels of both MDA and pro-inflammatory cytokines. CoQ10 and L-CoQ10 enhanced antioxidant capacity and Bcl-2, and downregulated caspase-3, Bax, p53, RIP3, MLKL, caspase-8 and TLR-4/NF-κB signaling. In conclusion, CoQ10 and L-CoQ10 effectively prevent CuSO₄ cardiotoxicity in rats. Attenuation of redox imbalance, TLR-4/NF-κB signaling, pro-inflammatory response, and necroptosis along with enhancement of antioxidant response mediated their cardioprotective efficacy. CoQ10 could be valuable in protecting people vulnerable to Cu toxicity.