Glimepiride prevents paraquat-induced Parkinsonism in mice: involvement of oxidative stress and neuroinflammation.

There is a growing number of epidemiological and molecular studies which suggest that diabetes is associated with an increased risk of Parkinson's disease (PD). Hence, in this study, the effect of glimepiride (GPD), a sulphonylurea (antidiabetic) on paraquat (PQT)-induced Parkinsonism was evaluated in mice. Thirty-six mice were randomly divided into six groups (n = 6) and treated orally for 21 consecutive days as follows: Group 1: vehicle (10 mL/kg), Group 2: PQT (10 mg/kg, i.p., twice per week for 3 weeks), Group 3-5: GPD (1, 2 or 4 mg/kg) + PQT (10 mg/kg, i.p., twice per week for 3 weeks), Group 6: GPD (4 mg/kg, p.o.). The effects of the treatment on motor coordination were evaluated using the rotarod performance, bar and open field tests while working memory was assayed using Y-maze test. Paraquat injection induced significant decrease in falling time, number of crosses and percentage alternation behaviour with a concomitant increase in the duration of cataleptic behaviour in the rotarod, open field, Y-maze and bar tests, respectively, which was ameliorated by GPD treatment. PQT also increased lipid peroxidation, peroxynitrite and TNF-α generations as well as deficit in superoxide dismutase and GSH activities in the midbrain. PQT-induced oxidative stress and neuroinflammation was attenuated by GPD treatment. Findings from this study showed that GPD prevents PQT-induced motor dysfunction, memory impairment, oxidative stress and neuroinflammation through enhancement of antioxidant defense system and inhibition of pro-inflammatory cytokine release. Thus, GPD could be a potential adjunct in the management of Parkinsonism.