Fisetin protects against renal injury and fibrosis evoked by diesel particulate matter via downregulation of IL-23/mTOR/S6K-b1 signaling and caveolin-1 expression in rats

Abstract

Numerous risk factors were identified for the incidence of renal injury and fibrosis among which is environmental pollution whereas air pollution by diesel particulate matter (PM) represents one of the most serious factors especially in developing countries. The present study aimed to explore the potential renoprotective effects of fisetin; a natural flavonoid against diesel PM-induced renal injury and fibrosis and clarify the underlying molecular mechanisms. For this purpose, adult Wistar albino rats received diesel PM (0.064 mg/kg/via oral gavage, three times/week) and were co-treated with fisetin (2.5 mg/Kg/via oral gavage/ day) for six weeks and compared with age-matched normal control group (NC). Kidney functions were assessed in serum samples while kidneys were harvested for biochemical and histological examination. Compared to NC group, diesel PM-administrated rats displayed elevated level of lipocalin-2 (Lcn-2) and kidney dysfunction along with renal histological changes that were alleviated markedly by fisetin. Concurrent treatment with fisetin significantly lowered the renal levels of NF-κB, IL-23 in addition to other inflammatory mediators including IL-17, TNF-α and IL-6. Also, diesel PM-administrated rats co-treated with fisetin showed downregulation of mTOR/S6K-b1 signaling besides a significant decrease in the renal expression of caveolin-1. This was associated with marked attenuation of interstitial fibrosis in the renal tissues of diesel PM-administrated rats. In conclusion, these findings proved for the first time that fisetin could exert renoprotective effects against renal injury and fibrosis induced by diesel PM probably via downregulation of IL-23/mTOR/S6K-b1 signaling along with decreasing renal caveolin-1 expression.