Iron toxicity mediated by oxidative stress enhances tissue damage in an animal model of diabetes.

Sampaio, Ana Flávia Santos; Silva, Maísa; Dornas, Waleska Claudia Amaral; Costa, Daniela Caldeira; Silva, Marcelo Eustáquio; Santos, Rinaldo Cardoso dos; Lima, Wanderson Geraldo de; Pedrosa, Maria Lúcia

Iron toxicity mediated by oxidative stress enhances tissue damage in an animal model of diabetes.

Date

2014

Authors

Sampaio, Ana Flávia Santos

Silva, Maísa

Dornas, Waleska Claudia Amaral

Costa, Daniela Caldeira

Silva, Marcelo Eustáquio

Santos, Rinaldo Cardoso dos

Lima, Wanderson Geraldo de

Pedrosa, Maria Lúcia

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 ratsweremaintainedwith orwithout 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 proteinmodification, amarker of oxidative stress, was consistently higher (p\0.01) in the tissues of the iron-treated rats with diabetes. Moreover, a significant positive correlationwas found betweenROS production andironpancreas 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.

Keywords

Heart, Pancreas, Reactive oxygen species

Citation

SAMPAIO, A. F. S. et al. Iron toxicity mediated by oxidative stress enhances tissue damage in an animal model of diabetes. BioMetals, v. 27, p. 349-361, 2014. Disponível em: <http://link.springer.com/article/10.1007%2Fs10534-014-9717-8>. Acesso em: 19 fev. 2017.