Renoprotective effect of saxagliptin and Hibiscus sabdariffa Linn extract in Nω-nitro-L-arginine methyl ester-induced hypertensive nephropathy in male albino rats: the role of proinflammatory and fibrogenic cytokines

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Objective The purpose of this paper is to evaluate the possible prophylactic effects of saxagliptin (SAX), a dipeptidyl peptidase 4 inhibitor, and Hibiscus sabdariffa Linn extract (HSE) and their combination against Nω-nitro-l-arginine methyl ester (l-NAME)-induced hypertensive nephropathy in rats; in addition, their effects on proinflammatory and fibrogenic cytokines involved in renal injury induced by hypertension were investigated. Materials and methods Rats were randomly divided into five groups (eight each) as follows: control group; l-NAME-treated group (50 mg/kg/day in drinking water); SAX+l-NAME-treated group (10 mg/kg/day postoperatively); HSE+l-NAME-treated group (100 mg/kg/day post operatively); SAX+HSE+l-NAME-treated group that received the same doses. Systolic blood pressure was measured. Kidney function tests (blood urea nitrogen, serum creatinine, total protein contents in 24-h urine, and creatinine clearance rate) and renal tissue oxidative biomarkers (malondialdehyde, glutathione, and glutathione peroxidase activity) were assessed. Proinflammatory cytokines (tumor necrosis factor-α and interleukin-6) levels were assessed in renal tissue homogenate; in addition, renal tissue transforming growth factor-β1 mRNA expression level was assayed. Histopathological analysis of the kidney and scoring were also performed. Results Administration of either SAX or HSE for 8 weeks attenuated l-NAME-induced increased oxidative stress, inflammation, and fibrosis in the kidney of rats, associated with improvement of the impaired renal function and histopathological changes, but their combination was found to be more effective in the protection against l-NAME-induced hypertensive renal damage than each drug alone. Conclusion A combination of SAX and HSE protected the kidney tissue against l-NAME-induced hypertensive nephropathy through their antioxidant, anti-inflammatory, and antifibrotic activities.