Nephroprotective effect of cilostazol and verapamil against thioacetamide-induced toxicity in rats may involve Nrf2/HO-1/NQO-1 signaling pathway

摘要

Cilostazol and verapamil are widely used cardiovascular drugs, explored a beneficial effect on different organs-induced toxicities. We investigated whether the Nrf2 (nuclear erythroid factor 2) and its downstream pathway are involved in the protective role of these drugs against TAA-induced renal damage. Renal biomarkers (creatinine and urea) and histopathology were observed. Antioxidant and oxidant indicators; superoxide dismutase (SOD), reduced glutathione (GSH), malondialdehyde (MDA) and total nitrite (NO) were also measured. Antioxidant markers like; Nrf2/hemoxegenase-1 (HO-1) and NADPH quinone oxidoreductase-1 (NQO-1) expressions were determined by ELISA and immunohistochemistry. Cilostazol and verapamil pretreatment improved serum creatinine and urea elevation. Examined drugs also have an ameliorative effect on TAA-induced elevation in MDA and NO activities and antioxidant enzymes; SOD and GSH. Additionally, the pretreated drugs significantly up-regulated Nrf2/HO-1/NQO-1 expression levels. In conclusion, cilostazol and verapamil exerted their protective effects partially via a Nrf2/HO-1/NQO-1 activation pathway with anti-oxidant roles.