Chymase inhibitor prevents the development and progression of non-alcoholic steatohepatitis in rats fed a high-fat and high-cholesterol diet

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-β,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. © 2017 the authors