Chymase inhibitor prevents the development and progression of non-alcoholic steatohepatitis in rats fed a high-fat and high-cholesterol diet.
J Pharmacol Sci
; 134(3): 139-146, 2017 Jul.
Article
en En
| MEDLINE
| ID: mdl-28673635
ABSTRACT
The effect of the chymase inhibitor TY-51469 on the development and progression of non-alcoholic steatohepatitis (NASH) was evaluated in rats fed a high-fat and high-cholesterol (HFC) diet. To evaluate the preventive effect of TY-51469 on the development of NASH, stroke-prone spontaneously hypertensive rat 5 (SHRSP5)/Dmcr rats were fed either a normal or HFC diet for 8 weeks, and concurrently administered either placebo or TY-51469 (1 mg/kg per day). To evaluate the effect of TY-51469 on the survival rate, TY-51469 was administered either concurrently with HFC diet (pretreated group) or 8 weeks after HFC diet at which point NASH had developed (posttreated group). Eight weeks after HFC diet, significant increases of steatosis, fibrosis and chymase-positive cells were observed in liver from the placebo-treated rats. Significant increases of myeloperoxidase, transforming growth factor-ß, matrix metalloproteinase-9, and collagen I mRNA levels were also observed. However, all parameters were significantly attenuated in the TY-51469-treated group. A survival rate of the placebo-treated group fed the HFC diet was 0% at 14 weeks. In comparison, the rates of TY-51469-pretreated and TY-51469-posttreated groups were 100% and 50% at 14 weeks, respectively. Chymase inhibitor may be applicable to preventing the development and progression of NASH.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sulfonamidas
/
Tiofenos
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Colesterol en la Dieta
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Inhibidores Enzimáticos
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Quimasas
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Dieta Alta en Grasa
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Enfermedad del Hígado Graso no Alcohólico
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Pharmacol Sci
Asunto de la revista:
FARMACOLOGIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Japón