Impaired Insulin Signaling Molecules in Triceps Muscle of Diethyl Hexyl Phthalate Treated Rat is Amelioreted by Antioxidant Vitamins

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Karundevi Balasubramanian


Available toxicological testing in animals and in vitro test, supported by limited human data, provide
evidence linking Diethyl hexyl phthalate (DEHP) and its metabolites to a wide range of adverse effects in
the reproductive tracts, liver, skeletal muscle, lungs, kidney and fetus. Recently there has been growing
concern for the impact of plastic; polyvinylchloride (PVC) based endocrine disruptors like DEHP affects
the function of endocrines and other organs in human beings and animals. Previous studies have shown
that exposure to DEHP results in elevated level of blood glucose, decrease in serum insulin and
testosterone level. However, specific effects of DEHP on insulin signaling molecules in triceps muscle;
an organ involved in the regulation of glucose homeostasis has received only little attention. Healthy
adult male albino rats of Wistar strain (Rattus norvegicus) were divided into four groups: Group I:
Control; Groups II and III: DEHP treated (dissolved in olive oil at a dose of 10 and 100 mg/kg body
weight, respectively, once daily through oral intubation for 30 days); and Group IV: DEHP (100 mg/kg
body weight) plus vitamins E (50 mg/kg body weight) and C (100 mg/kg body weight) dissolved in olive
oil and distilled water, respectively, once daily through oral intubation for 30 days. After the completion
of treatments, animals were euthanized and perfused (whole body); triceps was dissected out and
subjected to assessment of various parameters. Our results demonstrate that DEHP treatment induces
ROS and lipid peroxidation. Furthermore, DEHP treatment significantly decreased the levels of insulin
receptor, membrane GLUT4 protein as well as it reduces glucose uptake, oxidation and glycogen in
skeletal muscle due to decreased serum insulin level. Antioxidant vitamins (C & E) have significant
protective role against the adverse effect of DEHP on these tissues of adult male albino rat. All together,
these results suggest that DEHP exposure induces lipid peroxidation which disrupts the membrane
integrity and thus the insulin receptor and membrane GLUT4 proteins leading to reduced glucose
oxidation in triceps muscle. Supplementation of vitamins (C & E) prevented the DEHP-induced changes.

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