Role of hesperidin in modulating antioxidant enzymes in the brain of rats exposed to Nickel Chloride

This study aimed to investigate the effects of hesperidin on the gene expression of antioxidant enzymes catalase (Cat), superoxide dismutase (Sod), and glutathione peroxidase (Gpx) in the brain and their enzymatic activities in the brain and serum of rats exposed to nickel. Forty-eight male Wistar rats were divided into 6 groups: control group, nickel group (nickel chloride 20 mg/kg), hesperidin group (100 mg/kg), and three nickel + hesperidin groups at doses of 50, 100, and 200 mg/kg. Hesperidin was administered via gavage, and nickel was injected intraperitoneally for 21 days. The gene expression of Sod, Cat, and Gpx enzymes was examined using quantitative polymerase chain reaction (qPCR), and the activity of these enzymes in serum and brain tissue was assessed by standard biochemical methods. Immunohistochemistry was also used to analyze the expression of Sod1 protein in brain tissue. Exposure to nickel chloride significantly suppressed Sod, Cat, and Gpx enzymatic activities in both brain and serum tissues of rats ( P < 0.05 to P < 0.01). Hesperidin at 200 mg/kg significantly restored Sod and Cat activities in the brain by approximately 95.74 % and 80.35 %, respectively ( P < 0.05), and all doses (50–200 mg/kg) increased Gpx activity ( P < 0.01 to P < 0.001). In serum, hesperidin administration at doses of 100 mg/kg (44.36±13.7 U/mL) and 200 mg/kg (47.78±6.23 U/mL) significantly increased Cat activity compared with the nickel-exposed group (19.17±8.20 U/mL) ( P < 0.01). Moreover, the 200 mg/kg dose markedly enhanced Sod activity (36.78±9.86 U/mL) relative to the nickel group (16.60±3.67) ( P < 0.001). Nickel significantly downregulated Cat and Gpx gene expression ( P < 0.01 to P < 0.001), with no recovery after hesperidin treatment. In contrast, hesperidin at all doses significantly upregulated Sod gene expression ( P < 0.01 to P < 0.001). Sod1 protein expression in the brain was markedly reduced by nickel ( P < 0.0001), while hesperidin increased its expression at all doses ( P < 0.01 to P < 0.0001). Hesperidin, especially at higher doses, shows significant protective effects against nickel-induced oxidative damage.