Thymoquinone and curcumin combination protects cisplatin-induced kidney injury, nephrotoxicity by attenuating NFκB, KIM-1 and ameliorating Nrf2/HO-1 signalling

被引:57
作者
Al Fayi, Majed [1 ,2 ]
Otifi, Hassan [3 ]
Alshyarba, Mishari [4 ]
Dera, Ayed A. [1 ,2 ]
Rajagopalan, Prasanna [1 ,2 ]
机构
[1] King Khalid Univ, Coll Appl Med Sci, Dept Clin Lab Sci, Abha, Saudi Arabia
[2] King Khalid Univ, Coll Appl Med Sci, Cent Res Lab, Abha, Saudi Arabia
[3] King Khalid Univ, Coll Med, Dept Pathol, Abha, Saudi Arabia
[4] King Khalid Univ, Coll Med, Dept Surg, Abha, Saudi Arabia
关键词
Thymoquinone; curcumin; cisplatin; nephrotoxicity; acute kidney injury; KIM-1; Nfr2; HO-1; Akt; RENAL ISCHEMIA/REPERFUSION INJURY; OXIDATIVE STRESS; MECHANISMS; TOXICITY; NEUROTOXICITY; PURIFICATION; EXPRESSION; QUERCETIN; APOPTOSIS; PULMONARY;
D O I
10.1080/1061186X.2020.1722136
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
This study evaluates the protective effects of Thymoquinone (Tq) and Curcumin (Cur) in models of cisplatin-induced renal toxicity. Proliferation studies were carried out in HEK-293 cells. Cisplatin(ip) 5 mg/kg BW was used to induce renal injury in Sprague-Dawley rats. 50 mg/kg BW Tq + 100 mg/kg BW Cur, with or without cisplatin-treatment were administered for 5 days. Tq + Cur combination synergistically reduced the proliferation inhibition of HEK-293 cells resulted from cisplatin treatment and brought down cisplatin-induced apoptosis in these cells. In vitro studies revealed serum levels of BUN, creatinine, CK and pro-inflammatory cytokines like TNF-alpha, IL-6 and MRP-1 to be elevated in the cisplatin-treated group while reducing glomerular filtration rate. Tq + Cur treatment significantly improved these conditions. The antioxidant enzyme levels and mitochondrial ATPases were restored upon treatment, which were lessened in the cisplatin-treated group. Cisplatin induced the expression of KIM-1, which was brought down by the combination treatment. Tq + Cur treatment increased the expressions of phosphorylated Akt, Nrf2 and HO-1 proteins while decreasing the levels of cleaved caspase 3 and NF kappa B in kidney homogenates. In summary, Tq + Cur had protective effects on cisplatin-induced nephrotoxicity and renal injury, which could be mediated by up-regulation of survival signals like Akt, Nrf2/HO-1 and attenuation of KIM-1, NF kappa B.
引用
收藏
页码:913 / 922
页数:10
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