a Department of Pharmacology, Faculty of Medicine , Minia University , Minia , Egypt.
b Department of Histology, Faculty of Medicine , Minia University , Minia , Egypt.
Toxicol Mech Methods. 2019 Feb;29(2):146-152. doi: 10.1080/15376516.2018.1528648. Epub 2018 Dec 21.
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.
西洛他唑和维拉帕米是广泛应用于心血管的药物，研究它们对不同器官毒性的有益作用。我们研究了 Nrf2（核红细胞因子 2）及其下游途径是否参与这些药物对 TAA 诱导的肾损伤的保护作用。观察了肾生物标志物（肌酐和尿素）和组织病理学。还测量了抗氧化和氧化指标；超氧化物歧化酶（SOD）、还原型谷胱甘肽（GSH）、丙二醛（MDA）和总亚硝酸盐（NO）。通过 ELISA 和免疫组织化学测定抗氧化标记物，如 Nrf2/血红素加氧酶-1（HO-1）和 NADPH 醌氧化还原酶-1（NQO-1）的表达。西洛他唑和维拉帕米预处理可改善血清肌酐和尿素升高。研究药物还对 TAA 诱导的 MDA 和 NO 活性及抗氧化酶升高有改善作用；SOD 和 GSH。此外，预处理药物显著上调了 Nrf2/HO-1/NQO-1 的表达水平。总之，西洛他唑和维拉帕米通过 Nrf2/HO-1/NQO-1 激活途径发挥部分保护作用，具有抗氧化作用。
