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, Katsuyuki Tanabe, K. Hirokoshi-Kawahara, Hitoshi Sugiyama, Y. Sakai, Hirofumi 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

Fingerprint

Epoprostenol
Medical problems
Type 1 Diabetes Mellitus
Rats
Kidney
Diabetic Nephropathies
Transforming Growth Factor beta1
Animals
Hepatocyte Growth Factor
Albuminuria
Macrophages
Thromboxanes
Streptozocin
Hypertrophy
Chronic Kidney Failure
Smooth Muscle Myocytes
Muscle
ONO 1301
Actins
Monocytes

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry

Cite this

Intermittent administration of a sustained-release prostacyclin analog ONO-1301 ameliorates renal alterations in a rat type 1 diabetes model. / Yamasaki, H.; Maeshima, Y.; Nasu, T.; Saito, D.; Tanabe, Katsuyuki; Hirokoshi-Kawahara, K.; Sugiyama, Hitoshi; Sakai, Y.; Makino, Hirofumi.

In: Prostaglandins Leukotrienes and Essential Fatty Acids, Vol. 84, No. 3-4, 03.2011, p. 99-107.

Research output: Contribution to journalArticle

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