title: Phthalate is associated with insulin resistance in adipose tissue of male rat: role of antioxidant vitamins.
abstract: Diethyl hexyl phthalate (DEHP) is a plasticizer, commonly used in a variety of products, including lubricants, perfumes, hairsprays and cosmetics, construction materials, wood finishers, adhesives, floorings and paints. DEHP is an endocrine disruptor and it has a continuum of influence on various organ systems in human beings and experimental animals. However, specific effects of DEHP on insulin signaling in adipose tissue are not known. Adult male albino rats of Wistar strain were divided into four groups. Control, DEHP treated (dissolved in olive oil at a dose of 10, and 100 mg/kg body weight, respectively, once daily through gastric intubations for 30 days) and DEHP + vitamin E (50 mg/kg body weight) and C (100 mg/kg body weight) dissolved in olive oil and distilled water, respectively, once daily through gastric intubations for 30 days. After the completion of treatment, adipose tissue was dissected out to assess various parameters. DEHP treatment escalated H(2)O(2) and hydroxyl radical levels as well as lipid peroxidation in the adipose tissue. DEHP impaired the expression of insulin signaling molecules and their phosphorelay pathways leading to diminish plasma membrane GLUT4 level and thus decreased glucose uptake and oxidation. Blood glucose level was elevated as a result of these changes. Supplementation of vitamins (C & E) prevented the DEHP-induced changes. It is concluded that DEHP-induced ROS and lipid peroxidation disrupts the insulin signal transduction in adipose tissue and favors glucose intolerance. Antioxidant vitamins have a protective role against the adverse effect of DEHP.
authors.affiliation: Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Sekkizhar Campus, Taramani, Chennai 600113, India.
authors.forename: Parsanathan
authors.initials: P
authors.lastname: Rajesh
authors.forename: Sampath
authors.initials: S
authors.lastname: Sathish
authors.forename: Chinnapaiyan
authors.initials: C
authors.lastname: Srinivasan
authors.forename: Jayaraman
authors.initials: J
authors.lastname: Selvaraj
authors.forename: Karundevi
authors.initials: K
authors.lastname: Balasubramanian
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants; D019390:Arrestins / Q000096:biosynthesis / Q000187:drug effects; D001205:Ascorbic Acid / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance / Q000517:prevention & control; D051275:Glucose Transporter Type 4 / Q000096:biosynthesis / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D015398:Signal Transduction / Q000187:drug effects; D051780:Sterol Regulatory Element Binding Protein 1 / Q000096:biosynthesis / Q000187:drug effects; D014810:Vitamin E / Q000494:pharmacology*; D000071557:beta-Arrestins
chemical_list: D000975:Antioxidants; D019390:Arrestins; D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D017382:Reactive Oxygen Species; C495694:Slc2a4 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D000071557:beta-Arrestins; D014810:Vitamin E; D006861:Hydrogen Peroxide; D004051:Diethylhexyl Phthalate; D005947:Glucose; D001205:Ascorbic Acid