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

研究成果: Article査読

116 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1166-1172
ページ数7
ジャーナルNephrology Dialysis Transplantation
23
4
DOI
出版ステータスPublished - 2008 4月
外部発表はい

ASJC Scopus subject areas

  • 腎臓病学
  • 移植

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