Thymoquinone nanoparticles protect against cisplatin-induced nephrotoxicity in Ehrlich carcinoma model without compromising cisplatin anti-cancer efficacy

Cisplatin (CISP) is an effective chemotherapy used in the treatment of various types of cancer, but it causes nephrotoxicity and other adverse effects. Thymoquinone (THY) is an effective anti-inflammatory and antioxidant compound, which might protects against many chemotherapies associated toxicities. However, THY applications are hindered by its poor solubility and low bioavailability. This study evaluated the efficacy of a novel nanoparticle (NP) encapsulting THY to overcome its poor solubility, enhance its bioavilability, efficacy for the protection against CISP-induced nephrotoxicity in an Ehrlich solid carcinoma (ESC) mice model. Four treatment groups were included: 1) control, 2) tumour, 3) CISP, and 4) CISP + NP THY. The results showed that NP THY was effective in preventing CISP-induced kidney toxicity in ESC mice and improved its function and pathology. NP THY effectively ameliorated CISP-induced oxidative stress conditions in the kidney tissue via increasing the levels of antioxidants both non-enzymatic (GSH) and enzymatic (SOD and CAT). NP THY, also, significantly reduced CISP-induced kidney inflammation by reducing TNF-α, IL-1β, and NF-kB levels. NP THY didn’t hinder the antitumor activity of CISP as shown by tumour weight and histological examination data. In conclusion, NP THY could be an adjuvant therapy to CISP cancer treatment to prevent associated nephrotoxicity and other adverse effects without compromising CISP antitumor efficacy.