Oxidative stress induced by methotrexate alone and in the presence of methanol in discrete regions of the rodent brain, retina and optic nerve.
The vulnerability of the nervous system due to methanol (MeOH) intoxication is a well known fact and reports on the production of free radicals due to MeOH exposure and their involvement in excitotoxicity and neuronal apoptosis are being increasingly reported. We report on MeOH induced free radical changes and oxidative damages to proteins in the discrete regions of rat brain, retina and optic nerve. The present study used rats administered with methotrexate (MTX) to induce folate deficiency. Three groups of animals, namely saline control, MTX control, MTX-MeOH group were tested. The rats were injected intraperitoneally with MeOH (3 g/kg). After 24 h of MeOH administration, the levels of free radical scavengers, superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione levels were estimated in the six discrete regions of brain (cerebral cortex, cerebellum, midbrain, pons medulla, hippocampus and hypothalamus), retina and optic nerve specimens. The levels of protein thiol, protein carbonyl and lipid peroxidation were also estimated and the expression of HSP70 in the hippocampus was analyzed by Western blot. Marked reduction in the levels of glutathione in the MTX-MeOH group in relation to MTX control was observed and found to be increased in MTX control in relation to saline control. Increased protein carbonyls and decreased protein thiols were documented in all the specimens tested. In addition, marked expression of HSP70 was observed in the hippocampus. The present investigation suggest that MeOH exposure results in increased generation of free radicals and significant protein oxidative damage and attempts to study the underlying mechanisms involved might reveal more insights to our existing knowledge on MeOH intoxication and related areas.
Rajamani
Rathinam
R
Department of Physiology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Taramani, Chennai, India.
Muthuvel
Arumugham
A
Senthilvelan
Manohar
M
Sheeladevi
Rathinasamy
R
D000818:Animals; D001921:Brain / Q000187:drug effects*; D002374:Catalase / Q000378:metabolism; D004359:Drug Therapy, Combination; D005561:Formates / Q000097:blood; D005565:Formiminoglutamic Acid / Q000378:metabolism; D005786:Gene Expression Regulation; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D000432:Methanol / Q000097:blood / Q000633:toxicity*; D008727:Methotrexate / Q000633:toxicity*; D009900:Optic Nerve / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects*; D013438:Sulfhydryl Compounds / Q000097:blood; D013482:Superoxide Dismutase / Q000097:blood
D005561:Formates; D018840:HSP70 Heat-Shock Proteins; D013438:Sulfhydryl Compounds; C030544:formic acid; D005565:Formiminoglutamic Acid; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D000432:Methanol; D008727:Methotrexate