Antioxidant and Cytoprotective Effects of Biosynthesized Zinc Oxide Nanoparticles by Nigella sativa Against Cisplatin-Induced Testicular Damage in Mice

Abstract

Oxidative stress-induced apoptosis is one of the main reasons for male infertility. Investigations have indicated that metal nanoparticles synthesized by medicinal plants can reduce testicular tissue damage. We investigate the green synthesized zinc oxide nanoparticles (ZnO NPs) using Nigella sativa extract effects on cisplatin (Cis)-induced testicular tissue injury in male mice. Thirty adult male mice were divided into five groups including control, Cis, ZnO NPs (25 mg kg⁻¹) + Cis, extract (200 mg kg⁻¹) + Cis, and ZnO NPs/extract (200 mg kg⁻¹) + Cis. The experiment was carried out over a 14-day period, with a single IP injection of Cis (7.5 mg kg⁻¹) administered on the fifth day. Hematoxylin and eosin (H&E) staining was employed for histopathological evaluation. Malondialdehyde (MDA) content in tissue was determined by the thiobarbituric acid method. Gene expression levels were assessed using real-time quantitative PCR (qPCR). Severe histopathological damage to testicular tissue was observed in the Cis-treated group. Treatment with ZnO nanoparticles derived from N. sativa extract markedly attenuated testicular tissue damage and led to an improvement in the Johnson score. ZnO NPs synthesized using N. sativa extract significantly upregulated antioxidant-related genes, including glutathione peroxidase (GPx), superoxide dismutase (SOD), and nuclear factor erythroid 2–related factor 2 (Nrf2), while downregulating apoptosis-associated markers such as Bax and caspase-3 (p  < 0.05). Moreover, tissue MDA levels were notably reduced compared to the Cis-treated group (p  < 0.05). Our findings demonstrate that ZnO NPs synthesized with N. sativa exert a significant protective effect against Cis-induced testicular damage, likely through the inhibition of oxidative stress and apoptotic pathways.