Original Paper

Amelioration of Established Diabetic Nephropathy by Combined Treatment with SMP-534 (Antifibrotic Agent) and Losartan in db/db Mice
Eiji Sugaru^a, Tsutomu Nakagawa^a, Michiko Ono-Kishino^a, Jun Nagamine^a, Teruhisa Tokunaga^b, Makoto Kitoh^c, W. Ewan Hume^b, Ryu Nagata^b, Mutsuo Taiji<sup>a

a</sup>Pharmacology Research Laboratories;
^bChemistry Research Laboratories, and
^cTechnology Research and Development Center, Chemical Synthesis Laboratories, Dainippon Sumitomo Pharma Co., Ltd, Drug Research Division, Osaka, Japan

Address of Corresponding Author

Nephron Exp Nephrol 2007;105:e45-e52 (DOI: 10.1159/000097603)

  Key Words

• Diabetic nephropathy
• Fibrosis
• Losartan
• Urinary albumin
• Established renal lesion

  Abstract

Background/Aims: Diabetic nephropathy is the main cause of end-stage renal disease. Previously we have demonstrated that SMP-534 (an antifibrotic agent) prevents the development of diabetic nephropathy in db/db mouse and that combined treatment with SMP-534 and losartan (antihypertensive agents) markedly prevents the development of diabetic nephropathy compared with single treatment. SMP-534 or losartan was prophylactically administered to db/db mice before the onset of diabetic nephropathy. In the present study, we evaluated the efficacy of combined treatment when administration was started after the onset of diabetic nephropathy. Methods:db/db mice were raised untreated until 17 weeks of age, by which time increase of urinary albumin was noted, and then treated with SMP-534 and/or losartan for another 8 weeks. Biochemical and histological analyses were performed at 25 weeks of age. Results: Combined treatment with SMP-534 and losartan markedly prevented the increase ofurinary albumin and ameliorated the progression of mesangial matrix expansion, even when administration was started long after the increase of urinary albumin. Conclusion: The study results indicate that a combination of SMP-534 and losartan might be a valuable therapeutic approach for the treatment of diabetic nephropathy even when administration is started after the onset of diabetic nephropathy.

Copyright © 2007 S. Karger AG, Basel

  Author Contacts

Mutsuo Taiji, PhD
Dainippon Sumitomo Pharma Co., Ltd, Drug Research Division
Pharmacology Research Laboratories, Discovery Pharmacology Group I
3-1-98 Kasugadenaka, Konohana-ku, Osaka 554-0022 (Japan)
Tel. +81 6 6466 5264, Fax +81 6 6466 5182, E-Mail mutsuo-taiji@ds-pharma.co.jp

  Article Information

Received: March 20, 2006
Accepted: August 25, 2006
Published online: November 30, 2006
Number of Print Pages : 8
Number of Figures : 5, Number of Tables : 1, Number of References : 36