Zinc (Zn) is one of the essential trace elements and has numerous physiological functions. Zn acts as an antioxidant and also as a part of other antioxidant related proteins, such as metallothionein (MT) and Zn-copper superoxide dismutase. Zn deficiency often occurs in patients with diabetes. Therefore, the effect of Zn deficiency or Zn supplementation on diabetes-induced cardiac and renal pathogeneses has been explored. Diabetes was induced by streptozotocin (STZ) in mice and rats. Zn deficiency was induced by chronic treatment of diabetic mice with Zn chelator N,N,N,N-Tetrakis(2-pyridylmethyl)-1,2-ethylenediamine (TPEN) for 4 months. For Zn supplementation study, diabetic mice or rats were treated with Zn for 3 months. Inflammation, fibrosis, and histopathological changes in the heart and kidney of these diabetic mice and rats were examined by western blotting assay, immunohistochemical and fluorescent staining. Results showed that diabetes induced cardiac and renal oxidative damage, inflammation and fibrosis, which were reversed by Zn supplementation that also induced cardiac and renal MT synthesis. Furthermore, Zn deficiency was found to significantly enhance the renal damage induced by diabetes. Several clinical observations also support the preventive effect of Zn in the development of diabetic cardiomyopathy and nephropathy. Therefore, Zn plays an important role in the protection of the heart and kidney against diabetes-induced oxidative damage, inflammation, and fibrosis. These studies suggested that diabetic patients should be monitored and treated for Zn deficiency to avoid the acceleration of diabetes-induced cardiac and renal injury.
[1]Jilin Univ, Hosp 2, Dept Nephrol, Changchun 130041, Jilin Province, Peoples R China.
[2]Univ Louisville, Dept Pediat, KCHRI, Louisville, KY 40292 USA.
[3]Jilin Prov Peoples Hosp, Dept Nephrol, Changchun, Peoples R China.
[4]Wenzhou Med Coll, Chinese Amer Res Inst Diabet Complicat, Wenzhou, Peoples R China.
[5]Jilin Univ, Hosp 1, Urinary Dis Diag & Treatment Ctr, Changchun 130041, Jilin Province, Peoples R China.
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