Counteracting effects of Ethanolic extract of on Perfluorooctanoic acid-induced cardiotoxicity: insights into Keap1-Nrf2/PPARα pathways.

Perfluorooctanoic acid (PFOA) is a synthetic chemical belonging to per and poly-fluoroalkyl substances. It persists in the environment and accumulates in human bodies, leading to significant health concerns. (garlic) is acknowledged for its nutritional and anti-oxidative properties. Current research investigated the efficacy of ethanolic extract against PFOA-induced cardiotoxicity. Fifty adult albino rats were grouped equally into five groups: control, vehicle, (300 mg/kg), PFOA (25 mg/kg), and PFOA and . Rats were daily gavaged with treatments for 8 weeks. Serum samples were used for measuring lactate dehydrogenase (LDH), total cholesterol, and triglycerides (TG) levels. Cardiac tissues were used for assessing oxidative stress biomarkers (heme oxygenase1 (HO1), catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA)), and nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB). Also, the gene expression for nuclear factor erythroid-derived 2-like 2 (Nrf2), Kelch-like ECH-associated protein1 (Keap1), and peroxisome proliferator-activated receptor α (PPAR α) was determined. Cardiac tissues had undergone histopathological and immunohistochemical examination for caspase-3. Results revealed that PFOA exposure decreased the anti-oxidant enzymes (HO1, CAT, SOD), and markedly elevated levels of both MDA and NF-κB. PFOA inhibited the Nrf2 pathway as presented by the downregulated Nrf2 and upregulated Keap1 genes. Additionally, PFOA disturbed lipid metabolism via PPAR α downregulation. These changes were supported by histopathological changes and increased caspase-3 immunoexpression. A combination of extract with PFOA provided significant protection against the aforementioned changes. Results suggested that is an effective natural product that can attenuate PFOA-induced cardiotoxicity.