Ameliorative potential of sinensetin against paraquat induced renal damage by regulating oxidative, inflammatory, apoptotic and histopathological profile in male albino rats

Abstract

Background: Paraquat (PQ) is an extremely lethal, water-soluble and non-selective herbicide that is used globally due to its low cost and high efficacy. It exerts strong toxic effects on humans as its exposure leads to free radicals’ production. Sinensetin (SNS) is a natural flavonoid with strong anti-cancer, anti-inflammatory and anti-oxidant potentials. Objective: The present study was planned to ascertain the attenuative effect of SNS against PQ induced renal damage in rats. Methods: Forty eight rats were distributed into four groups: control group, PQ-administered group (5 mg/kg), PQ + SNS co-administered group (5 mg/kg and 20 mg/kg) and SNS administered group (20 mg/kg). Results: PQ administration considerably decreased the activities of anti-oxidant enzymes i.e., catalase (CAT), glutathione reductase (GSR), superoxide dismutase (SOD), glutathione peroxide (GPx), glutathione-S-transferase (GST) activities and glutathione (GSH) contents, while reactive oxygen species (ROS) and malondialdehyde (MDA) contents were upsurged. PQ treatment markedly augmented the levels of creatinine, urobilinogen, urea, KIM-1 and NGAL, while significantly decreased albumin protein as well as creatinine clearance. Moreover, the findings of our experiment revealed that PQ notably escalated inflammatory indices i.e., interleukin-1β (IL-1β), nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) level and cyclooxygenase-2 (COX-2) activity. Furthermore, PQ intoxication significantly increased Bax, Caspase-3, Caspase-9 level and lowered Bcl-2 level as well as induced histopathological anomalies in kidneys. However, SNS + PQ co-treatment efficiently averted all the PQ-induced renal damages in the rats. Conclusion: The current study indicates that SNS can be used to treat PQ-instigated renal toxicity due to its anti-oxidant, anti-inflammatory and anti-apoptotic properties.