AbstractThis study aimed to assess the renopreventive effect of the angiotensin converting enzyme inhibitor (ACEI), enalapril, and/or vitamin D receptor (VDR) activator, paricalcitol, on streptozotocin (STZ) diabetes-induced nephropathy and to elucidate the mechanisms of action through investigation of the effects on renal oxidative stress, antioxidant defense system and expressions of TNF-α, P53, caspase-3, and Bcl-2. Diabetes mellitus was induced in fasting male Wistar rats by single intraperitoneal injection of STZ (45 mg /kg b.w.) dissolved in citrate buffer pH 4.5. Ten days after STZ injection, the diabetic rats were treated with enalapril (25 mg/l of drinking water) and/or paricalcitol (8 µg/kg b.w.per os) dissolved in 5% DMSO daily for 4 weeks. The obtained data revealed that the treatment of diabetic Wistar rats with enalapril and/or paricalcitol led to a significant decrease in the elevated serum urea, uric acid, creatinine and sodium, potassium levels; thereby reflecting improvement of the impaired kidney function. The deteriorated kidney lipid peroxidation, GSH content and GST and catalase activities in diabetic rats were significantly ameliorated as a result of treatment with enalapril and/or paricalcitol. The elevated fasting and post-prandial serum glucose levels and the lowered serum insulin and C-peptide levels were also improved. Moreover, the treatment of diabetic rats successfully prevented the diabetes-induced histopathological deleterious changes of kidney and islets of Langerhans of pancreas. In association, the immunohistochemically detected pro-inflammatory cytokine TNF-α and apoptotic mediators P53 and caspase-3 were remarkably decreased in kidney of diabetic rats as a result of treatment, while the expression of anti-apoptotic protein Bcl-2 was increased. Based on these findings, it can be concluded that enalapril and paricalcitol can prevent STZ diabetes-induced nephropathy though amelioration of the glycemic state and antioxidant defense system together with the suppression of oxidative stress, inflammation and apoptosis.
Effects of enalapril and paricalcitol treatment on diabetic nephropathy and renal expressions of TNF-α, P53, Caspase-3 and Bcl-2 in STZ-induced diabetic rats
