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

Abstract

Objectives: 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. Methods: Four treatment groups were included: 1) control, 2) tumour, 3) CISP, and 4) CISP + NP THY. Results: 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. Conclusions: 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.

Keywords

• Cisplatin
• Thymoquinone
• Nephrotoxicity
• Ehrlich
• Antioxidant
• Anti-inflammatory