title: Intermittent administration of a sustained-release prostacyclin analog ONO-1301 ameliorates renal alterations in a rat type 1 diabetes model.
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.
authors.affiliation: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yamasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Maeshima
authors.forename: T
authors.initials: T
authors.lastname: Nasu
authors.forename: D
authors.initials: D
authors.lastname: Saito
authors.forename: K
authors.initials: K
authors.lastname: Tanabe
authors.forename: K
authors.initials: K
authors.lastname: Hirokoshi-Kawahara
authors.forename: H
authors.initials: H
authors.lastname: Sugiyama
authors.forename: Y
authors.initials: Y
authors.lastname: Sakai
authors.forename: H
authors.initials: H
authors.lastname: Makino
mesh_terms: D000818:Animals; D003404:Creatinine / Q000652:urine; D003692:Delayed-Action Preparations; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000378:metabolism; D011725:Pyridines / Q000008:administration & dosage* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D003404:Creatinine; D003692:Delayed-Action Preparations; D006442:Glycated Hemoglobin; D017228:Hepatocyte Growth Factor; D011725:Pyridines; D053773:Transforming Growth Factor beta1; C105488:ONO 1301