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

J Drug Target. 2020 Nov;28(9):913-922. doi: 10.1080/1061186X.2020.1722136. Epub 2020 Feb 5.


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.

Keywords: Akt; KIM-1; Nfr2/HO-1; Thymoquinone; acute kidney injury; cisplatin; curcumin; nephrotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / prevention & control*
  • Animals
  • Benzoquinones / pharmacology*
  • Cell Proliferation
  • Cisplatin / adverse effects*
  • Curcumin / pharmacology*
  • Cytokines
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • HEK293 Cells
  • Heme Oxygenase-1 / drug effects
  • Hepatitis A Virus Cellular Receptor 1 / drug effects
  • Humans
  • Kidney Function Tests
  • Male
  • NF-E2-Related Factor 2 / drug effects
  • NF-kappa B / drug effects
  • Oxidative Stress / drug effects
  • Rats


  • Benzoquinones
  • Cytokines
  • Drug Combinations
  • Hepatitis A Virus Cellular Receptor 1
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Heme Oxygenase-1
  • Curcumin
  • thymoquinone
  • Cisplatin