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Intermittent administration of a sustained-release prostacyclin analog ONO-1301 ameliorates renal alterations in a

H Yamasaki1, Y Maeshima, T Nasu

  • 1Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.

Prostaglandins, Leukotrienes, and Essential Fatty Acids
|December 24, 2010
PubMed

Insights

This study shows that ONO-1301, a prostacyclin analog, effectively treats diabetic nephropathy in rats. It reduces kidney damage and fibrosis by increasing hepatocyte growth factor (HGF).

Area of Science:

  • Nephrology
  • Endocrinology
  • Pharmacology

Background:

  • Diabetic nephropathy is a leading cause of end-stage renal disease.
  • Current treatments for diabetic nephropathy are limited.
  • ONO-1301 is a novel prostacyclin analog with thromboxane synthase inhibitory activity.

Purpose of the Study:

  • To investigate the therapeutic potential of ONO-1301 in a rat model of type 1 diabetic nephropathy.
  • To evaluate the effects of sustained-release ONO-1301 (SR-ONO) on kidney damage markers.

Main Methods:

  • Streptozotocin (STZ)-induced diabetic rats were treated with SR-ONO every 3 weeks.
  • Kidney tissues were analyzed at Week 14 for pathological changes.
  • Levels of albuminuria, TGF-beta1, alpha-SMA, and HGF were measured.

Main Results:

  • SR-ONO significantly reduced albuminuria and glomerular hypertrophy.
  • It suppressed mesangial matrix accumulation and inflammatory cell infiltration.
  • SR-ONO increased glomerular HGF levels and counteracted TGF-beta1-induced fibrosis.

Conclusions:

  • Intermittent administration of SR-ONO shows therapeutic efficacy in diabetic nephropathy.
  • The mechanism may involve HGF induction, counteracting TGF-beta1's pro-fibrotic effects.
  • SR-ONO represents a potential treatment strategy for diabetic kidney disease.

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