Reno-protective potential of sudachitin to mitigate paraquat instigated renal toxicity via regulating Nrf2/Keap1 pathway: An inflammatory, apoptotic and histopathological assessment.

ABSTRACT

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., a control group, PQ (5mg/kg) intoxicated, PQ (5mg/kg) + SCN (20mg/kg) exposed & SCN (20mg/kg) only administrated group. Our findings explored that exposure to PQ lessened the expressions of Nrf2 and its cytoprotective genes while escalating the expression of keap1. Furthermore, PQ intoxication reduced the enzymatic activity of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSR), & glutathione (GSH), while upregulating the levels of malondialdehyde (MDA) & reactive oxygen species (ROS). Moreover, intoxication to PQ 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, exposure to 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-1ß), & cyclo-oxygenase-2 (COX-2). Moreover, PQ administration upregulated the expression of Bax and Caspase-3 while downregulating the expressions of Bcl-2. Besides, PQ exposure prompted various histopathological damages in renal tissues. Nonetheless, SCN substantially restored aforementioned alterations in renal tissues owing to its anti-oxidative, anti-inflammatory and anti-apoptotic potential.