Effect of Hachimijiogan against Renal Dysfunction and Involvement of Hypoxia‐Inducible Factor‐1α in the Remnant Kidney Model

Hiroshi Oka,Michiko Jo,Naotoshi Shibahara,Hirozo Goto,Ikuo Saiki,Hiroaki Sakurai,Yutaka Shimada,Keiichi Koizumi,Shin Nakamura,Yue Zhou,Takako Fujimoto,Koichi Tsuneyama

doi:10.1155/2011/348686

Abstract

In chronic renal failure, hypoxia of renal tissue is thought to be the common final pathway leading to end-stage renal failure. In this study the effects of hachimijiogan, a Kampo formula, were studied with respect to hypoxia-inducible factor (HIF). Using remnant kidney rats, we studied the effects of hachimijiogan on renal function in comparison with angiotensin II receptor blocker. The result showed that oral administration of hachimijiogan for seven days suppressed urinary protein excretion and urinary 8-OHdG, a marker of antioxidant activity, equally as well as oral administration of candesartan cilexetil. In contrast, the protein volume of HIF-1α in the renal cortex was not increased in the candesartan cilexetil group, but that in the hachimijiogan group was increased. In immunohistochemical studies as well, the expression of HIF-1α of the high-dose hachimijiogan group increased compared to that of the control group. Vascular endothelial growth factor and glucose transporter 1, target genes of HIF-1α, were also increased in the hachimijiogan group. These results suggest that hachimijiogan produces a protective effect by a mechanism different from that of candesartan cilexetil.

Highlights

In recent years, it has been clear that chronic kidney disease (CKD) is an important risk factor for cardiovascular diseases and mortality and has been the focus of considerable attention [1]
We studied the effects of hachimijiogan on renal function in comparison with angiotensin II receptor blocker
Vascular endothelial growth factor and glucose transporter 1, target genes of hypoxia-inducible factor (HIF)-1α, were increased in the hachimijiogan group. These results suggest that hachimijiogan produces a protective effect by a mechanism different from that of candesartan cilexetil

Summary

Introduction

It has been clear that chronic kidney disease (CKD) is an important risk factor for cardiovascular diseases and mortality and has been the focus of considerable attention [1]. There are various causes for the early stage of CKD, but there is a common pathway in advanced CKD as represented by interstitial fibrosis, glomerular sclerosis, and nephron destruction [3]. It has been reported that chronic hypoxia in the kidney is the final common pathway to end-stage renal failure [4, 5]. Activation of HIF stimulates numerous downstream target genes and protects tissue from hypoxia [6]. This effect is suggested by reports, which showed that cobalt ameliorates renal injury of renal disease model rats [7], and vascular

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Discussion

Conclusion