%0 Journal Article %A Fayi, Majed Al %A Otifi, Hassan %A Alshyarba, Mishari %A Dera, Ayed A %A Rajagopalan, Prasanna %D 2020 %T Thymoquinone and curcumin combination protects cisplatin-induced kidney injury, nephrotoxicity by attenuating NFκB, KIM-1 and ameliorating Nrf2/HO-1 signalling %U https://tandf.figshare.com/articles/journal_contribution/Thymoquinone_and_curcumin_combination_protects_cisplatin-induced_kidney_injury_nephrotoxicity_by_attenuating_NF_B_KIM-1_and_ameliorating_Nrf2_HO-1_signalling/11806938 %R 10.6084/m9.figshare.11806938.v1 %2 https://tandf.figshare.com/ndownloader/files/21556467 %K Thymoquinone %K curcumin %K cisplatin %K nephrotoxicity %K acute kidney injury %K KIM-1 %K Nfr2/HO-1 %K Akt %X

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-α, 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 NFκB 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, NFκB.

%I Taylor & Francis