Abdel-Salam_2012_J.Basic.Clin.Physiol.Pharmacol_23_61

Abstract Background Gabapentin a structural analog of gamma-aminobutyric acid GABA is used in the treatment of neuropathic pain in multiple sclerosis Methods This study investigated the effect of gabapentin on oxidative stress in a model of brain demyelination evoked by intracerebral injection i.c.i of ethidium bromide 10 muL of 0.1 Rats received saline control or gabapentin at 100 or 300 mg/kg orally daily for 10 days prior to injection of ethidium bromide Rats were euthanized 1 day later and then the levels of reduced glutathione GSH glutathione peroxidase GPx activity lipid peroxidation malondialdehyde MDA nitrite acetyl cholinesterase AChE and paraoxonase activities were assessed in the brain cortex in different treatment groups Results Ethidium bromide resulted in increased oxidative stress in the cortex 1 day after its injection Malondialdehyde increased by 30.2 whereas GSH decreased by 17.6 GPx activity was inhibited by 78.6 Brain nitrite increased by 55.4 AChE activity decreased by 33.4 and paraoxonase activity decreased by 27.5 In ethidium bromide treated rats gabapentin administered at 300 mg/kg increased cortical MDA by 66 GSH was unaltered by gabapentin but GPx activity decreased by 54.3 by the higher dose of gabapentin Nitrite decreased by 21.4 and 29.2 after 100 and 300 mg/kg of gabapentin respectively AChE activity increased by 28.6 and 69.3 by 100 and 300 mg/kg of gabapentin respectively Paraoxonase activity showed 83.3 and 73 decreases by 100 and 300 mg/kg of gabapentin respectively Conclusions These results suggest that gabapentin increases brain lipid peroxidation and decreases brain antioxidant enzymes in this model of chemical demyelination.