A Novel Vitamin K<sub>1</sub> 2,3-Epoxide Reductase (VKOR) Inhibitor, 3-Acetyl-5-Methyltetronic Acid, Reduces Experimental Glomerulonephritis
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- UCHIDA Masashi
- Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries, Inc., 6–10–1 Tebiro, Kamakura, Kanagawa 248–8555, Japan
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- SAKAGUCHI Yuka
- Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries, Inc., 6–10–1 Tebiro, Kamakura, Kanagawa 248–8555, Japan
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- MIYAMOTO Yohei
- Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries, Inc., 6–10–1 Tebiro, Kamakura, Kanagawa 248–8555, Japan
Bibliographic Information
- Other Title
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- A Novel Vitamin K₁ 2,3-Epoxide Reductase (VKOR) Inhibitor, 3-Acetyl-5-Methyltetronic Acid, Reduces Experimental Glomerulonephritis
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Abstract
Excessive proliferation of mesangial cells is observed in various types of glomerular disease including glomerulonephritis (GN), which is progressive in nature and eventually results in end-stage renal disease (ESRD). Vitamin K1 2,3-epoxide reductase (VKOR) and the vitamin K-dependent growth arrest-specific gene 6/Axl pathway play a key role in mesangial cell proliferation in GN. In the present study, we indicate the potential of a VKOR inhibitor, 3-acetyl-5-methyltetronic acid (AMT), to prevent the proliferation of glomerular mesangial cells and suppress the progression of GN. AMT was administered intravenously to rats once daily for 12 days and a mouse anti-Thy1 monoclonal antibody was injected intravenously after the AMT treatment on Day 6. Creatinine clearance (CCr) significantly increased and the albumin-to-creatinine ratio (ACR) significantly decreased in the AMT-treated group of the Thy-1 GN rats. In addition, glomerular and tubular damage was improved histopathologically in the AMT-treated group. AMT did not affect blood coagulation due to its unique pharmacokinetic properties. The concentration of AMT reached the IC50 for VKOR in kidney, but not in liver. A novel VKOR inhibitor, AMT, reduced renal mesangial cell proliferation and could be a supportive treatment for GN.
Journal
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- Journal of Veterinary Medical Science
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Journal of Veterinary Medical Science 74 (7), 863-869, 2012
JAPANESE SOCIETY OF VETERINARY SCIENCE
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Details 詳細情報について
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- CRID
- 1390282681406205440
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- NII Article ID
- 130001879778
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- NII Book ID
- AA10796138
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- COI
- 1:STN:280:DC%2BC38visFCqsA%3D%3D
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- ISSN
- 13477439
- 09167250
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- NDL BIB ID
- 023910760
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- PubMed
- 22322189
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed