Ameliorative Potential of Sudachitin Against Paraquat Induced Renal Toxicity in Rats Via Regulating Nrf2/Keap1 Pathway: An Inflammatory, Apoptotic and Histopathological Assessment

Paraquat (PQ) is a noxious herbicide which is well known for its adverse effects on vital organs including kidneys. Sudachitin (SCN) is a plant derived flavone that is obtained from Citrus sudachi and demonstrates a range of pharmacological potentials. This investigation was executed to assess the protective effects of SCN to counteract PQ instigated renal damage in albino rats (Rattus norvegicus). Twenty-four rats were apportioned in 4 different groups i. e., control group, PQ (5 mg/kg) intoxicated group, PQ (5 mg/kg)+SCN (20 mg/kg) cotreated group and SCN (20 mg/kg) only administrated group. Our findings revealed that exposure to PQ reduced the expressions of Nrf2 (nuclear factor erythroid 2-related factor 2) and its cytoprotective genes while escalating the expression of keap1. Furthermore, PQ intoxication reduced the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSR), heme-oxygenase-1 (HO-1) and glutathione (GSH) contents while increasing the levels of malondialdehyde (MDA) and reactive oxygen species (ROS). Moreover, PQ exposure significantly increased the levels of neutrophil gelatinous-associated lipocalin (NGAL), urea, kidney injury molecule-1(KIM-1) as well as creatine while reducing creatine clearance. Additionally, PQ upregulated the levels of inflammatory markers including interleukin-6 (IL-6), tumor necrosis- α (TNF- α), nuclear factor- κB (NF-κB), interleukin 1beta (IL-1β), and cyclo-oxygenase-2 (COX-2). Moreover, PQ administration upregulated the expression of Bax (Bcl-2-associated X protein) and (cysteine-aspartic acid protease) Caspase-3 while downregulating the expressions of (B-cell lymphoma 2 protein) Bcl-2. Besides, PQ exposure prompted various histopathological damages in renal tissues. Nonetheless, SCN substantially restored aforementioned alterations in the renal tissues owing to its anti-oxidative, anti-inflammatory and anti-apoptotic potential.