Pomegranate nanoparticle mitigates cisplatin-induced testicular toxicity and improves cisplatin anti-cancer efficacy in Ehrlich carcinoma model

Abstract

Cisplatin (CISP) ranks among the most used chemo-therapeutic agents with exceptional efficacy against testicular cancer among other diverse types of cancers. However, it has been associated with nephrotoxicity among other side effects. Pomegranate (PE) is an effective anti-inflammatory and antioxidant compound, protecting against several chemotherapy-linked toxicities. The use of PE are limited due to its low bioavailability and poor solubility. We investigated the potential of a novel nanoparticle (NP) encapsulating PE formulation to surmount its poor solubility, improve its bioavailability, and augment its protective efficacy against CISP-induced testicular toxicity in an Ehrlich solid carcinoma (ESC) mice model. All animals were randomly grouped into four treatment groups: 1) control, 2) tumor, 3) CISP, and 4) CISP + PE-NPs. The results obtained demonstrated that PE-NPs efficiently prevented testicular toxicity induced by CISP in ESC mice and enhanced its functions. PE-NPs effectively improved CISP-induced oxidative stress in testicular tissues by elevating the levels of antioxidants (GSH, SOD and CAT). Importantly, PE-NPs, also, substantially decreased testicular inflammation induced by CISP, via reducing the levels of IL-1β, TNF-α, and NF-kB. PE-NPs did not impede the CISP’s antitumor activity as shown by histological examination data and tumor weight. It is, therefore, conceivable that PE-NPs may serve as an adjuvant therapy to CISP in the treatment of cancer, to ameliorate the associated testicular toxicity and other unwanted effects without compromising the antitumor efficacy of CISP.

Keywords

• Cisplatin
• Pomegranate
• Testicular toxicity
• Ehrlich
• Anti-inflammatory
• Nano formulation