title: Iron toxicity mediated by oxidative stress enhances tissue damage in an animal model of diabetes.
abstract: Although iron is a first-line pro-oxidant that modulates clinical manifestations of various systemic diseases, including diabetes, the individual tissue damage generated by active oxidant insults has not been demonstrated in current animal models of diabetes. We tested the hypothesis that oxidative stress is involved in the severity of the tissues injury when iron supplementation is administered in a model of type 1 diabetes. Streptozotocin (Stz)-induced diabetic and non-diabetic Fischer rats were maintained with or without a treatment consisting of iron dextran ip at 0.1 mL day(-1) doses administered for 4 days at intervals of 5 days. After 3 weeks, an extensive increase (p < 0.001) in the production of reactive oxygen species (ROS) in neutrophils of the diabetic animals on iron overload was observed. Histological analysis revealed that this treatment also resulted in higher (p < 0.05) tissue iron deposits, a higher (p < 0.001) number of inflammatory cells in the pancreas, and apparent cardiac fibrosis, as shown by an increase (p < 0.05) in type III collagen levels, which result in dysfunctional myocardial. Carbonyl protein modification, a marker of oxidative stress, was consistently higher (p < 0.01) in the tissues of the iron-treated rats with diabetes. Moreover, a significant positive correlation was found between ROS production and iron pancreas stores (r = 0.42, p < 0.04), iron heart stores (r = 0.54, p < 0.04), and change of the carbonyl protein content in pancreas (r = 0.49, p < 0.009), and heart (r = 0.48, p < 0.02). A negative correlation was still found between ROS production and total glutathione content in pancreas (r = -0.50, p < 0.03) and heart (r = -0.45, p < 0.04). In conclusion, our results suggest that amplified toxicity in pancreatic and cardiac tissues in rats with diabetes on iron overload might be attributed to increased oxidative stress.
authors.affiliation: Program of Health and Nutrition, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil.
authors.forename: Ana Flávia S
authors.initials: AF
authors.lastname: Sampaio
authors.forename: Maisa
authors.initials: M
authors.lastname: Silva
authors.forename: Waleska C
authors.initials: WC
authors.lastname: Dornas
authors.forename: Daniela C
authors.initials: DC
authors.lastname: Costa
authors.forename: Marcelo E
authors.initials: ME
authors.lastname: Silva
authors.forename: Rinaldo C
authors.initials: RC
authors.lastname: Dos Santos
authors.forename: Wanderson G
authors.initials: WG
authors.lastname: de Lima
authors.forename: Maria Lúcia
authors.initials: ML
authors.lastname: Pedrosa
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D019190:Iron Overload / Q000139:chemically induced / Q000150:complications / Q000378:metabolism; D007505:Iron-Dextran Complex / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism; D013311:Streptozocin; D014018:Tissue Distribution
chemical_list: D017382:Reactive Oxygen Species; D013311:Streptozocin; D007505:Iron-Dextran Complex