Sciadopitysin attenuates paraquat induced renal toxicity by modulating Nrf2/Keap-1 pathway in male albino rats

Abstract

Paraquat (PQ) is a herbicide that has the potential to instigate nephrotoxicity in animals and human. Sciadopitysin (SPS) is a biflavonoid that is extracted from Taxus cuspidate and displays diverse biological activities including anti-oxidant, anti-inflammatory and anti-apoptotic. Therefore, the present investigation was designed to evaluate the mitigative potential of SPS against PQ prompted renal toxicity in albino rats. 48 male albino rats were divided into 4 groups, such as control group, PQ treated group (5 mgkg -1 ), PQ + SPS co-treated group (5 mgkg -1 and 2 mgkg -1 respectively) and only SPS treated group (2 mgkg -1 ). The exposure of PQ significantly reduced Nrf-2 as well as anti-oxidant enzymes expression, while increasing Keap-1 expression. Moreover, anti-oxidant enzymes such as, glutathione reductase (GSR), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione-S-transferase (GST), heme oxygenase-1 (HO-1) and glutathione (GSH) activities were decreased. However, in PQ-treated rats malondialdehyde (MDA) and reactive oxygen species (ROS) contents were significantly increased. PQ exposure also increased the serum level of urea, urinary protein, urobilinogen and creatinine while decreased creatinine clearance and albumin protein levels. Moreover, KIM-1 and NGAL levels were also increased in PQ exposed rats. Additionally, inflammatory indices including nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2) activity were increased in PQ administrated rats. Besides, it escalated the Bax and Caspase-3 expression. Contrarily, a substantial decrease was observed in anti-apoptotic marker, Bcl-2 expression. The exposure of PQ also induced significant histopathological damages in renal tissues. Nevertheless, SPS supplementation recovered all these damages due to its anti-apoptotic, anti-oxidant and anti-inflammatory nature.