Oxidative stress and behavioral deficits in 3-nitropropionic acid-induced neurotoxicity in male mice: Neuroprotective effects of silymarin

Abstract Background 3-Nitropropionic acid (3-NP) is strongly believed to be a mitochondrial complex II irreversible inhibitor, leading to neural damages. Silymarin has been reported to exert various pharmacological manifestations including hepatoprotection, anti-inflammatory, anti-oxidant and cardioprotection. This study aimed to investigate neuroprotective features of silymarin against 3-Nitropropionic acid-induced neurotoxicity in male mice. Methods Six-week-old mice were received sub-chronic doses of 3-NP, intraperitoneally for 17 days. A group of mice were pretreated with silymarin (70 mg/kg/day, P.O.) for two weeks before 3-NP administration. Treatment group was received 3-NP for 17 days and then silymarin (70 mg/kg/day, P.O.) for 4weeks. At the end of the treatment schedule, animals were evaluated for behavioral alterations. Afterward, mice were sacrificed, neuronal damages in the hippocampus region of the brain tissues were performed by H&E staining, and the homogenates brain was used for evaluating the oxidative stress related parameters (Lipid peroxidation, nitric oxide, superoxide dismutase, glutathione, and total antioxidant capacity) and pro-inflammatory cytokine (TNF-α, IL-17, and IL-1β) levels. Results Our results indicated that 3-NP treatment significantly (p < 0.05) tends to reduce the motor coordination, memory, and neuronal antioxidant status while increased the pro-inflammatory cytokine levels. However, silymarin in both treatment and pretreatment protocols markedly (p < 0.05) attenuated the behavioral deficits, oxidative stress status, and neuroinflammation. Conclusion Results of the current study suggested that neuroprotective effect of silymarin against 3-NP-induced neurotoxicity might be due to mitigating oxidative stress status and provide insight into the therapeutic potential of silymarin.