Levetiracetam attenuates experimental ulcerative colitis through promoting Nrf2/HO-1 antioxidant and inhibiting NF-κB, proinflammatory cytokines and iNOS/NO pathways

Ulcerative colitis (UC) is a serious inflammatory disease of the colon. The pathogenic mechanisms of UC involve the activation of inflammatory and oxidative stress responses in the colon. Levetiracetam is an antiepileptic drug with anti-inflammatory and antioxidant effects. The aim of this study was to investigate the potential protective effect of levetiracetam against UC in a mouse model. UC was induced in mice by intrarectal administration of acetic acid and then mice were treated with levetiracetam (50 or 100 mg/kg/day, i.p.) for three days. The colonic tissue samples were dissected for biochemical, RT-PCR and immunofluorescence analysis. Results showed that levetiracetam treatment significantly decreased colonic mucosal injury as evidenced by the macroscopic and histopathological analysis. Levetiracetam induced Nrf2/HO-1 and antioxidants while reduced lipid peroxidation and myeloperoxidase activity in colon tissue. Levetiracetam treatment decreased NF-kappa B activity and the expression of proinflammatory mediators TNF-alpha, IL-6, IL-1 beta, IFN-gamma, MCP-1 and ICAM-1. The colonic levels of anti-inflammatory cytokines IL-10 and TGF-beta 1 were increased by levetiracetam treatment. Furthermore, levetiracetam significantly diminished iNOS expression and NO production in colon tissue. These findings suggest that levetiracetam ameliorates the severity of UC in mice through the regulation of inflammatory and oxidative responses.

Automated summary

This study aimed to investigate the potential protective effect of the antiepileptic drug levetiracetam against ulcerative colitis (UC) in mice. The results showed that levetiracetam can alleviate colonic mucosal injury in UC mice, promote antioxidant responses, reduce lipid peroxidation and myeloperoxidase activity, decrease inflammatory mediator expression, and increase anti-inflammatory cytokine levels.