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EF6265, a Novel Plasma Carboxypeptidase B Inhibitor, Protects Against Renal Dysfunction in Rat Thrombotic Glomerulonephritis Through Enhancing Fibrinolysis

EF6265, a Novel Plasma Carboxypeptidase B Inhibitor, Protects Against Renal Dysfunction in Rat Thrombotic Glomerulonephritis Through Enhancing Fibrinolysis

Yuko Muto, Kokichi Suzuki, Hiroyuki Iida, Hidemi Ishii

Nephron Exp Nephrol. 2007;106(4):e113-21.

PMID: 17622739

Abstract:

Background/aim:
Plasma carboxypeptidase B is a physiological fibrinolysis inhibitor. In the present study, the effects of EF6265, a novel specific plasma carboxypeptidase B inhibitor, on renal dysfunction in a rat thrombotic glomerulonephritis model were examined.
Methods:
The model was induced by injection of anti-glomerular basement membrane serum and lipopolysaccharide to rats. Renal microthrombosis was histologically evaluated by phosphotungstic acid-hematoxylin staining for fibrin thrombi. Renal dysfunction was evaluated on the basis of plasma levels of blood urea nitrogen as well as renal edemas and urine volume.
Results:
The glomerular microthrombi observed in a positive control group were significantly reduced after a short-term treatment (4 h) with EF6265 at a dose which enhanced fibrinolysis. The elevation of blood urea nitrogen and renal edema formation decreased, and the reduction of the urine volume improved after a long-term treatment (21 h) with EF6265. In addition, EF6265 had a protective activity against multiple organ dysfunction, because it reduced plasma lactate dehydrogenase and alanine aminotransferase levels and mortality in this model.
Conclusion:
EF6265, which inhibits plasma carboxypeptidase B, showed a protective effect on thrombotic renal dysfunction in thrombotic glomerulonephritis through enhancing the fibrinolysis.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42412297	CARBOXYPEPTIDASE-B rat			Price

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