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  • Title: The effect of gabapentin on oxidative stress in a model of toxic demyelination in rat brain.
    Author: Abdel-Salam OM, Khadrawy YA, Mohammed NA, Youness ER.
    Journal: J Basic Clin Physiol Pharmacol; 2012; 23(2):61-8. PubMed ID: 23089532.
    Abstract:
    BACKGROUND: Gabapentin, a structural analog of γ-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 μL 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.
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