Nevirapine mitigates monosodium glutamate induced neurotoxicity and oxidative stress changes in prepubertal mice

Abstract

Aim: We investigated the effects of nevirapine on changes in body weight, lipid peroxidation/antioxidant status, apoptotic markers and neuromorphology following monosodium glutamate-induced neurotoxicity in prepubertal mice. Material and Methods: Eighty male mice which were randomly divided into eight groups of ten mice each (n=10) were used. Mice in each group were administered oral vehicle, monosodium glutamate (MSG) at 2g/kg, or one of three doses of nevirapine (at 7.5, 15 and 30 mg/kg) alone or co-administered with MSG. Vehicle or nevirapine were administered daily for 28 days, while MSG was administered on days 1-7. On day 28, animals were euthanized and blood was collected for estimation of plasma malondialdehyde (MDA) and antioxidant levels; while sections of the cerebrum and hippocampus were either fixed and processed for general histology, or homogenized for the estimation of brain biochemical parameters. Results: Results showed that administration of nevirapine alone (or when co-administered with MSG) was associated with a reduction in weight gain, increase in plasma/brain MDA levels, morphologic/morphometric evidence of dose-related hypercellularity; and varying degrees of neuroprotection, with co-administration. Nitric oxide levels and caspase-3 activity increased only with MSG, while superoxide dismutase activity decreased. Conclusions: In conclusion, subchronic administration of nevirapine was associated with dose-related alterations of the measured parameters; indicating possible neuroprotection and mitigation of MSG neurotoxicity at some of the doses studied.