10.6084/m9.figshare.11806938.v1 Majed Al Fayi Majed Al Fayi Hassan Otifi Hassan Otifi Mishari Alshyarba Mishari Alshyarba Ayed A Dera Ayed A Dera Prasanna Rajagopalan Prasanna Rajagopalan Thymoquinone and curcumin combination protects cisplatin-induced kidney injury, nephrotoxicity by attenuating NFκB, KIM-1 and ameliorating Nrf2/HO-1 signalling Taylor & Francis Group 2020 Thymoquinone curcumin cisplatin nephrotoxicity acute kidney injury KIM-1 Nfr2/HO-1 Akt 2020-02-05 10:43:14 Journal contribution 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 <p>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. <i>In vitro</i> 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.</p>