title: Alteration in glutathione homeostasis and oxidative stress during the sequelae of trimethyltin syndrome in rat brain.
abstract: Trimethyltin (TMT), a by-product of tin, is used in a wide variety of industrial and agricultural purposes which serves as a model neurotoxicant in hippocampal neurodegeneration, and this could, in turn, be exploited for various therapeutic compounds essential for hippocampal neurodegeneration. Therefore, the present investigation explores the sequential changes in behavior, oxidative burden, and apoptosis following TMT administration in rat hippocampus. Male SD rats weighing 250 g were given single dose of 8.5 mg/kg TMT (i.p.) that resulted in "TMT syndrome" which begins at the third post-TMT exposure and continued till 21 days posttreatment. This resulted in behavioral alteration (aggression and spontaneous seizures), cognitive impairment as assessed by plus maze, and passive avoidance resulting in short-term memory deficits. These behavioral alterations were associated with an increase in oxidative stress. The levels of malondialdehyde, reactive oxygen species, and protein carbonyl were significantly increased (p < 0.001) in the TMT-treated rats after the third day of exposure and were maximum at day 14 postexposure. The glutathione system was not able to adapt rapidly in response to oxidative stress which resulted in imbalance in redox status. The imbalance in the redox state resulted in the death of neurons as seen by a significant increase in caspase activation at gene as well as protein level after TMT exposure on day 14, quoting an extent of changes. Therefore, it is proposed that behavioral deficits could be accounted by the impairment of endogenous glutathione homeostasis which resulted in death of neurons in the hippocampal region.
authors.affiliation: Department of Biophysics, Basic Medical Sciences Block, Panjab University, Chandigarh 160014, India.
authors.forename: Sukhwinder
authors.initials: S
authors.lastname: Kaur
authors.forename: Bimla
authors.initials: B
authors.lastname: Nehru
mesh_terms: D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D017931:DNA Primers; D005978:Glutathione / Q000378:metabolism*; D006706:Homeostasis; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013054:Spectrophotometry, Atomic; D014298:Trimethyltin Compounds / Q000097:blood / Q000378:metabolism / Q000633:toxicity*
chemical_list: D017931:DNA Primers; D014298:Trimethyltin Compounds; C046488:trimethyltin; D020169:Caspases; D005978:Glutathione