Nickel oxide nanoparticle (NiO NPs) has been widely used in various fields such as catalysts, radiotherapy, and nanomedicine. The aim of this study was to compare the effects of nickel oxide (NiO) and NiO NPs on oxidative stress biomarkers and histopathological changes in brain tissue of rats. In this study, 49 male rats were randomly divided into one control group and 6 experimental groups (n = 7). The control group received normal saline and the treatment groups received NiO and NiO NPs at doses of 10, 25, and 50 mg/kg intraperitoneally for 8 days. After 8 days, animal was sacrificed, brain excised, homogenized, centrifuged, and then supernatant was collected for antioxidant assays. The results showed that activity of GST in NiO NPs groups with doses of 10, 25, and 50 mg/kg (79.42 ± 4.24, p = 0.035; 78.77 ± 8.49, p = 0.041; 81.38 ± 12.39, p = 0.042 to 47.26 ± 7.17) and catalase in NiO NPs groups with concentrations of 25 and 50 mg/kg (69.95 ± 8.65 to 39.75 ± 5.11, p = 0.02) and (68.80 ± 4.18 to 39.75 ± 5.11 p = 0.027) were significantly increased compared with the control, respectively. Total antioxidant capacity in NiONPs group with doses of 50 mg/kg was significantly decreased (345.00 ± 23.62, p = 0.015 to 496.66 ± 25.77) compared with control. The GSH level in all doses NiO and NiONPs was significantly decreased compared with the control (p = 0.002). MDA level in NiONPs and NiO groups with doses of 50 mg/kg was significantly increased (13.03 ± 1.29, p = < 0.01; 15.61 ± 1.08, p = < 0.001 to 7.32 ± 0.51) compared with the control, respectively. Our results revealed a range of histopathological changes, including necrosis, hyperemia, gliosis, and spongy changes in brain tissue. Thus, increasing level of MDA, GST, and CAT enzymes and decreasing GSH and TAC and also histopathological changes confirmed NiONPs and NiO toxicity.
