Thymoquinone alleviates renal interstitial fibrosis and kidney dysfunction in rats with unilateral ureteral obstruction

Abstract

Unilateral ureteral obstruction (UUO) causes severe renal tubulointerstitial fibrosis. Because of many pharmacologic properties of thymoquinone (TQ), in this study, the effects of TQ against kidney fibrosis and dysfunction were investigated in rats with UUO. Forty male Wistar rats were divided into five groups: Sham operated, UUO, and the animals with UUO treated with losartan, captopril, or TQ. Collagen IV and transforming growth factor (TGF)‐β1 expressions, interstitial fibrosis, histological changes, and kidney function were assessed. UUO markedly increased renal expression of TGF‐β1 and collagen I and induced interstitial fibrosis (p < .001). Losartan, captopril, or TQ significantly downregulated the expression of these fibrotic markers and interstitial fibrosis (p < .01–p < .001). In UUO group, serum levels of urea and creatinine and protein excretion rate significantly increased, but glomerular filtration rate (GFR) and urine osmolarity showed a significant decrease (p < .001–p < .05). Administration of captopril and TQ caused no significant change in serum urea and protein excretion rate. Unlike losartan and captopril, TQ caused no significant alteration in GFR compared with Day 1. Losartan caused significant increases in serum urea and creatinine but significant decrease in urine osmolarity. TQ could be regarded as a potent therapeutic agent for treatment of UUO‐induced kidney fibrosis and dysfunction.

Lactacystin-induced kidney fibrosis: Protection by melatonin and captopril

“…Indeed, captopril decreased the concentration of soluble collagen in the LV of rats with combined continuous light and L-NAME-induced hypertension ( Simko et al, 2010 ), attenuated LV collagen deposition in SHR ( Zhao et al, 2015 ), and reduced LV fibrosis in mice with transverse aortic constriction ( Zhang et al, 2019 ) and Sprague-Dawley rats with L-NAME-induced hypertension ( Sonoda et al, 2017 ). Similarly, in kidneys captopril reduced interstitial renal fibrosis in neonatal dogs with partial urethral obstruction (PUO) ( Shirazi et al, 2007 ), ameliorated fibrosis in rats with PUO ( Shirazi et al, 2014 ), and downregulated interstitial fibrosis in rats with unilateral ureteral obstruction ( Hosseinian et al, 2019 ). In line with these data, our results show reduced intraglomerular, tubulointerstitial, and perivascular collagen accumulation and renal hydroxyproline concentration after 6 weeks of captopril administration in lactacystin-treated rats.…”

Thymoquinone alleviates liver fibrosis via miR‐30a‐mediated epithelial‐mesenchymal transition

“…TQ, as a natural product phytochemical, has the potential to control cancer cell proliferation as well as metastasis (Li et al, 2017; Mostofa et al, 2017). In addition, a growing body of evidence suggests that TQ has inhibitory effects on organ fibrosis (Bai et al, 2014; Hosseinian et al, 2019; Pourgholamhossein et al, 2016). For example, Bai et al (2014) found that TQ can reduce hepatic fibrosis and inflammation.…”