title: The effect of gabapentin on oxidative stress in a model of toxic demyelination in rat brain.
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.
authors.affiliation: Department of Toxicology and Narcotics, National Research Centre, Dokki, Cairo, Egypt. omasalam@hotmail.com
authors.forename: Omar M E
authors.initials: OM
authors.lastname: Abdel-Salam
authors.forename: Yasser Ashry
authors.initials: YA
authors.lastname: Khadrawy
authors.forename: Nadia A
authors.initials: NA
authors.lastname: Mohammed
authors.forename: Eman R
authors.initials: ER
authors.lastname: Youness
mesh_terms: D000588:Amines / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D003711:Demyelinating Diseases / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004996:Ethidium / Q000633:toxicity; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000077206:Gabapentin; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000588:Amines; D000975:Antioxidants; D003509:Cyclohexanecarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D004996:Ethidium