Abstract
OBJECTIVEIncreasing evidence suggests that Nigella sativa oil (NSO) and its principal bioactive constituents, thymoquinone (TQ), exhibit antioxidant, antihyperglycemic and renoprotective effects in streptozotocin (STZ)-induced diabetes in rats. However, the potential molecular mechanisms by which NSO and TQ may exert their actions in the diabetic kidney are still poorly characterized. This study was designed to investigate the effect of NSO and TQ treatment on the albuminuria, podocyte injury and the complex systems controlling the extracellular matrix proteins accumulation and angiogenesis in the STZ-induced model of diabetic nephropathy.MATERIALS AND METHODSAdult female Wistar rats were divided into four experimental groups (control, untreated STZ-diabetic, and NSO or TQ treated STZ-diabetic rats). The treated rats received 2 mL/kg NSO or 50 mg/kg TQ via oral gavage once a day for 10 weeks.RESULTSThe results showed that the albuminuria and the kidney weight/body weight ratio were increased in the diabetic rats compared with the control animals and they were significantly ameliorated by the treatment with NSO or TQ. The real-time PCR showed that the NSO and TQ treatment prevented diabetes-induced downregulation of mRNA expression of the podocyte-specific marker (podocin) as well as the mRNA overexpressions of collagen IV, transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor-A (VEGF-A) in the diabetic kidney. These results were also confirmed by immunohistochemistry.CONCLUSIONSNSO and TQ treatment decreased albuminuria in the experimental models of the diabetic nephropathy by the preservation of the podocyte function; along with the suppression of enhanced extracellular matrix gene expression through interfering with TGF-β1 production and angiogenesis.