Diabetogenic effects and pancreatic oxidative damage in rats subchronically exposed to arsenite.
Recent epidemiologic studies have associated chronic inorganic arsenic ((i)As) exposure with an increase in the prevalence of diabetes mellitus. Currently, the diabetogenic mechanism caused by (i)As exposure is unclear. However, it is recognized that (i)As contributes to oxidative stress in several organs and systems through generation of reactive oxygen species (ROS). ROS can function as signaling molecules to activate a number of cellular stress-sensitive pathways linked to insulin resistance and decreased insulin secretion. Male Wistar rats were administered sodium arsenite at 1.7 mg/kg (12 h), or water (controls) orally for 90 days. At the end of the 90 days of (i)As exposure hyperglycemia, hyperinsulinemia and low insulin sensitivity, evaluated by the homeostasis model assessment of insulin resistance, was observed. Arsenicals in pancreas of rats exposed to (i)As were significantly higher than the control group, being dimethyl and trimethyl metabolites the predominant arsenic species. The activity of pancreatic thioredoxin reductase was lower than the control group. Also, the levels of total glutathione and lipoperoxidation in pancreas increased significantly relative to the control group indicating the presence of stress and oxidative damage, respectively. These results represent an attempt to establish an animal model for in vivo studies of diabetogenic effects of chronic arsenic exposure.
Izquierdo-Vega
Jeannett A
JA
Sección Externa de Toxicología, Cinvestav, Col. San Pedro Zacatenco, Mexico DF.
Soto
Claudia A
CA
Sanchez-Peña
Luz C
LC
De Vizcaya-Ruiz
Andrea
A
Del Razo
Luz M
LM
D000818:Animals; D018053:Arsenites / Q000493:pharmacokinetics / Q000633:toxicity*; D001786:Blood Glucose / Q000032:analysis; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000633:toxicity; D005934:Glucagon / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D007150:Immunohistochemistry; D007333:Insulin Resistance; D015227:Lipid Peroxidation; D008297:Male; D023421:Models, Animal; D018384:Oxidative Stress; D010179:Pancreas / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017670:Sodium Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism
D018053:Arsenites; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D017670:Sodium Compounds; C017947:sodium arsenite; D005934:Glucagon; D013880:Thioredoxin-Disulfide Reductase; D005978:Glutathione