title: Differential susceptibility of brain regions to tributyltin chloride toxicity.
abstract: Tributyltin (TBT), a well-known endocrine disruptor, is an omnipresent environmental pollutant and is explicitly used in many industrial applications. Previously we have shown its neurotoxic potential on cerebral cortex of male Wistar rats. As the effect of TBT on other brain regions is not known, we planned this study to evaluate its effect on four brain regions (cerebellum, hippocampus, hypothalamus, and striatum). Four-week-old male Wistar rats were gavaged with a single dose of TBT-chloride (TBTC) (10, 20, and 30 mg/kg) and sacrificed on days 3 and 7, respectively. Effect of TBTC on blood-brain barrier (BBB) permeability and tin (Sn) accumulation were measured. Oxidative stress indexes such as reactive oxygen species (ROS), reduced and oxidized glutathione (GSH/GSSG) ratio, lipid peroxidation, and protein carbonylation were analyzed as they play an imperative role in various neuropathological conditions. Since metal catalyzed reactions are a major source of oxidant generation, levels of essential metals like iron (Fe), zinc (Zn), and calcium (Ca) were estimated. We found that TBTC disrupted BBB and increased Sn accumulation, both of which appear significantly correlated. Altered metal homeostasis and ROS generation accompanied by elevated lipid peroxidation and protein carbonylation indicated oxidative damage which appeared more pronounced in the striatum than in cerebellum, hippocampus, and hypothalamus. This could be associated to the depleted GSH levels in striatum. These results suggest that striatum is more susceptible to TBTC induced oxidative damage as compared with other brain regions under study.
authors.affiliation: Immunotoxicology Division, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, India.|Department of Biochemistry, Jamia Hamdard, Hamdard University, New Delhi, India.
authors.forename: Sumonto
authors.initials: S
authors.lastname: Mitra
authors.affiliation: Department of Biochemistry, Jamia Hamdard, Hamdard University, New Delhi, India.
authors.forename: Waseem A
authors.initials: WA
authors.lastname: Siddiqui
authors.affiliation: Immunotoxicology Division, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, India.
authors.forename: Shashi
authors.initials: S
authors.lastname: Khandelwal
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000032:analysis; D002540:Cerebral Cortex / Q000187:drug effects; D003342:Corpus Striatum / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007501:Iron / Q000032:analysis; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013054:Spectrophotometry, Atomic; D014220:Trialkyltin Compounds / Q000633:toxicity*; D015032:Zinc / Q000032:analysis
chemical_list: D017382:Reactive Oxygen Species; D014220:Trialkyltin Compounds; C011559:tributyltin; D007501:Iron; D005978:Glutathione; D015032:Zinc; D002118:Calcium
keywords: blood-brain barrier; brain regions; differential susceptibility; oxidative damage; tributyltin chloride