3-Nitropropionic acid (3-NP) is strongly believed to be an irreversible inhibitor of mitochondrial complex II, leading to neural damage. This study aimed to investigate the neuroprotective effects of silymarin against 3-NP-induced neurotoxicity in male mice. Six-week-old mice received subacute doses of 3-NP intraperitoneally for 17 days. Mice were given silymarin (70 mg/kg/day, P.O.) for 2 weeks before 3-NP administration or for 4 weeks after 3-NP administration. At the end of the treatment schedule, animals were evaluated for behavioral alterations. Subsequently, neuronal damage in the hippocampus region of the brain tissues, 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 were evaluated. Our results indicated that 3-NP treatment significantly (p < 0.05) tended to reduce motor coordination, memory, and neuronal antioxidant status while increasing 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. The results of the current study suggest that the neuroprotective effect of silymarin against 3-NP-induced neurotoxicity might be due to the mitigation of oxidative stress status and provide insight into the therapeutic potential of silymarin.
Keywords: 3-Nitropropionic acid; Neuroinflammation; Neurotoxicity; Oxidative stress; Silymarin.
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.