Intermittent administration of a sustained-release prostacyclin analog ONO-1301 ameliorates renal alterations in a rat type 1 diabetes model

H. Yamasaki, Y. Maeshima, T. Nasu, D. Saito, K. Tanabe, K. Hirokoshi-Kawahara, H. Sugiyama, Y. Sakai, H. Makino

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Diabetic nephropathy is the most common pathological disorder predisposing end-stage renal disease. ONO-1301 is a novel sustained-release prostacyclin analog possessing thromboxane (TX) synthase inhibitory activity. Here, we aimed to investigate the therapeutic efficacies of ONO-1301 in a rat type 1 diabetic nephropathy model. Streptozotocin (STZ)-induced diabetic rats received injections of slow-release form of ONO-1301 (SR-ONO) every 3 weeks. Animals were sacrificed at Week 14. SR-ONO significantly suppressed albuminuria, glomerular hypertrophy, mesangial matrix accumulation, glomerular accumulation of monocyte/macrophage, increase in glomerular levels of pro-fibrotic factor transforming growth factor (TGF)-beta1 and the number of glomerular alpha-smooth muscle actin (SMA)+ cells in diabetic animals. The glomerular levels of hepatocyte growth factor (HGF) were significantly increased in SR-ONO-treated diabetic animals. Taken together, these results suggest the potential therapeutic efficacy of intermittent administration of SR-ONO in treating diabetic nephropathy potentially via inducing HGF, thus counteracting the pro-fibrotic effects of TGF-beta1.

Original languageEnglish
Pages (from-to)99-107
Number of pages9
JournalProstaglandins Leukotrienes and Essential Fatty Acids
Volume84
Issue number3-4
DOIs
Publication statusPublished - Mar 2011

Keywords

  • Diabetic nephropathy
  • HGF
  • ONO-1301
  • Prostacyclin
  • TGF-beta1

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology

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