title: Consequences of tributyltin chloride induced stress in Leydig cells: an ex-vivo approach.
abstract: Tributyltin (TBT), a member of the organotin family, is a known endocrine disruptor. It persists long in the environment and is widely used in various industrial applications. This study was planned to understand its toxic influence on Leydig cells isolated from 28 day old wistar rats. In-vitro exposure to TBT-Chloride (TBTC) (300-3000 nM) reduced cell viability (DNA fragmentation, nuclear condensation and MTT assay) and affected testosterone production. TBTC induced both apoptotic and necrotic cell death (AnnexinV/PI binding assay). Involvement of calcium (Ca(2+)), redox imbalance (ROS, GSH and TBARS) and mitochondria in TBTC toxicity was evaluated by using Ca(2+) inhibitors (BAPTA-AM, EGTA, Ruthenium Red), free radical scavengers (NAC, C-Phycocyanin) and mitochondrial permeability transition pore inhibitor (Cyclosporine A). Protein expression analysis of phosphorylated MAPKinases (ERK1/2, JNK1/2, & p38), steroidogenic proteins (3β-HSD, StAR & TSPO) and apoptotic proteins (Bax, Bcl2) illustrates the cytotoxic and anti-steroidogenic activity of TBTC.
authors.affiliation: Immunotoxicology Division, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), P.O. Box 80, Mahatma Gandhi Marg, Lucknow-226001, India.
authors.forename: Sumonto
authors.initials: S
authors.lastname: Mitra
authors.affiliation: Immunotoxicology Division, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), P.O. Box 80, Mahatma Gandhi Marg, Lucknow-226001, India.
authors.forename: Ankit
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: Immunotoxicology Division, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), P.O. Box 80, Mahatma Gandhi Marg, Lucknow-226001, India.
authors.forename: Smita
authors.initials: S
authors.lastname: Khanna
authors.affiliation: Immunotoxicology Division, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), P.O. Box 80, Mahatma Gandhi Marg, Lucknow-226001, India. Electronic address: shashik.iitr@gmail.com.
authors.forename: Shashi
authors.initials: S
authors.lastname: Khandelwal
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D052244:Endocrine Disruptors / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism; D014220:Trialkyltin Compounds / Q000633:toxicity*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: C494828:Bax protein, rat; D002352:Carrier Proteins; D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D010750:Phosphoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D011963:Receptors, GABA-A; D014220:Trialkyltin Compounds; D051028:bcl-2-Associated X Protein; D000098682:Steroidogenic Acute Regulatory Protein; C069997:Tspo protein, rat; D013739:Testosterone; C011559:tributyltin; D015096:3-Hydroxysteroid Dehydrogenases; D020928:Mitogen-Activated Protein Kinases; D005978:Glutathione; D002118:Calcium
keywords: Leydig; Oxidative stress; Steroidogenesis; Testosterone; Tributyltin chloride