Cobalt ameliorates renal injury in an obese, hypertensive type 2 diabetes rat model

Shuichi Ohtomo, Masaomi Nangaku, Yuko Izuhara, Shunya Takizawa, Charles Van Ypersele De Strihou, Toshio Miyata

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Background. Chronic renal hypoxia is suspected to play a pathogenic role in the genesis of diabetic nephropathy (DN). Cobalt enhances the activity of the hypoxia-inducible factor (HIF), a key factor in the defence against hypoxia. Its long-term effect on DN is evaluated. Methods. Cobalt chloride was given to hypertensive, type 2 diabetic rats with nephropathy (SHR/NDmcr-cp). Treatment was initiated at the age of 13 weeks and continued for 26 weeks. Results. Cobalt did not correct hypertension and metabolic abnormalities (obesity, hyperglycaemia and hyperlipidaemia) but reduced proteinuria as well as histological kidney injury. Cobalt upregulated renal HIF-1alpha and HIF-2alpha expression and increased the expression of HIF-regulated genes, including erythropoietin, vascular endothelial growth factor and heme oxygenase-1. The renal expression of transforming growth factor (TGF)-beta and connective tissue growth factor (CTGF) was significantly reduced by cobalt. The renal expression of NADPH oxidase, a marker of oxidative stress, and the renal content of pentosidine, a marker of advanced glycation, were also significantly reduced by cobalt. Conclusions. Cobalt achieved renal protection independently of metabolic status and blood pressure. Its effect was attributed to the upregulation of HIF and HIF-regulated genes and to a mitigated advanced glycation and oxidative stress.

Original languageEnglish
Pages (from-to)1166-1172
Number of pages7
JournalNephrology Dialysis Transplantation
Volume23
Issue number4
DOIs
Publication statusPublished - 2008 Apr 1
Externally publishedYes

Keywords

  • Chronic hypoxia
  • Cobalt chloride
  • Diabetic nephropathy
  • Hypoxia inducible factor
  • Oxidative stress

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

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