The therapeutic potential of isosakuranetin against perfluorooctane sulfonate instigated cardiac toxicity via modulating Nrf‐2/Keap‐1 pathway, inflammatory, apoptotic, and histological profile

Abstract

AbstractPerfluorooctane sulfonate (PFOS) is a pervasive organic toxicant that damages body organs, including heart. Isosakuranetin (ISN) is a plant‐based flavonoid that exhibits a broad range of pharmacological potentials. The current investigation was conducted to evaluate the potential role of ISN to counteract PFOS‐induced cardiac damage in rats. Twenty‐four albino rats (Rattus norvegicus) were distributed into four groups, including control, PFOS (10 mg/kg) intoxicated, PFOS + ISN (10 mg/kg + 20 mg/kg) treated, and ISN (20 mg/kg) alone supplemented group. It was revealed that PFOS intoxication reduced the expressions of Nrf‐2 and its antioxidant genes while escalating the expression of Keap‐1. Furthermore, PFOS exposure reduced the activities of glutathione reductase (GSR), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S‐transferase (GST), Heme oxygenase‐1 (HO‐1) and glutathione (GSH) contents while upregulating the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Besides, PFOS administration upregulated the levels of creatine kinase‐MB (CK‐MB), troponin I, creatine phosphokinase (CPK), and lactate dehydrogenase (LDH). Moreover, the levels of tumor necrosis factor‐alpha (TNF‐α), nuclear factor kappa‐B (NF‐κB), interleukin‐6 (IL‐6), and interleukin‐1β (IL‐1β) were increased after PFOS intoxication. Additionally, PFOS exposure downregulated the expression of Bcl‐2 while upregulating the expressions of Bax and Caspase‐3. Furthermore, PFOS administration disrupted the normal architecture of cardiac tissues. Nonetheless, ISN treatment remarkably protected the cardiac tissues via regulating aforementioned dysregulations owing to its antioxidative, anti‐inflammatory, and antiapoptotic properties.