Biochemical, Immunohistochemical, Histopathological, and Apoptotic Evaluation of Nickel Oxide Nanoparticle- and Microparticle-Induced Testicular Toxicity in Male Rats.

Nickel oxide nanoparticles are engineered particles that are now widely used in medicine, agriculture, and industry applications. This study aimed to investigate subchronic testicular toxicity induced by nickel oxide (NiO) and nickel oxide nanoparticles (NiONPs) in rats by comparing oral, intraperitoneal (IP), and intravenous (IV) routes of administration. Forty-two male Wistar rats were used for the study, and seven groups were formed: control group, NiO oral (150 mg/kg), NiO IP (20 mg/kg), NiO IV (1 mg/kg), NiONP oral (150 mg/kg), NiONP IP (20 mg/kg), and NiONP IV (1 mg/kg). At the end of the 21 day treatment, we collected the testicular tissue of rats to measure biomarkers such as oxidative stress, apoptotic, and inflammatory levels to observe histopathological and immunohistochemical changes. NiO and NiONP treatment caused a decrease in antioxidant activities and AChE levels, an increase in MDA, IL-1β, IL-6, and 8-OHdG levels, a decrease in Bcl-2 expression, and an increase in caspase-3, Bax, and p53 expressions in apoptotic markers. In addition to histopathologic changes in the testicular tissue, an increase in expression of the endoplasmic reticulum stress marker GRP78 was also observed. In conclusion, NiONPs (especially NiONP IV) increased testicular toxicity by disrupting the oxidant-antioxidant balance more than NiO microparticles.