Quercetin and its potential therapeutic effects on aluminum phosphide-induced cardiotoxicity in rats: Role of NOX4, FOXO1, ERK1/2, and NF-κB.

Acute Aluminum phosphide (AlP) poisoning poses a serious global issue, yet the exact mechanisms behind AlP-induced cardiotoxicity are still not well understood. Moreover, there is no specific antidote available for AlP toxicity. Nevertheless, Quercetin (QE) has emerged as a promising therapeutic candidate in various contexts. Accordingly, our study aimed to evaluate the QE potential therapeutic effects against AlP-induced cardiotoxicity and the mechanisms underlying such effects. Rats were assigned into four groups: Group I (control group), Group II (vehicle (corn oil) group), Group III (AlP group) received a single dose of AlP (10 mg/kg body weight) dissolved in corn oil by oral gavage, and Group IV (AlP + QE group) received a single dose of QE (400 mg/kg body weight) dissolved in saline, one hour after AlP administration. AlP-induced cardiotoxicity was evidenced by the increase in cardiac troponin I (cTnI) as well as the hemodynamic, ECG, and histopathological abnormalities. The AlP group denoted a decrease of the antioxidant enzymes; catalase and SOD and an increase of the lipid peroxidation marker; MDA. This was associated with a notable increase in inflammatory cytokines (TNFα, IL-6, and IL1β), in addition to a significant upregulation of the expression of NOX4, FOXO1, ERK1/2, and NF-κB. Moreover, Caspase3, and BAX showed strong immunopositive expression, while Bcl-2 showed mild immunoexpression. On the other hand, treatment with QE showed an improvement in the cardiotoxic effects of AlP, as indicated by significant enhancements in biomarkers, functional assessments, and histopathological findings. These results suggest that QE may be a promising candidate for treating AlP-induced cardiotoxicity, attributed to its antioxidant, anti-inflammatory, and anti-apoptotic properties, particularly emphasizing the roles of NOX4, FOXO1, ERK1/2, and NF-κB.
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