Cholesterol-induced stimulation of postinflammatory liver fibrosis

We studied the effect of high-cholesterol diet and factors inhibiting 3-hydroxy-3-methyl-glutaryl coenzyme A reductase on the development of liver fibrosis in C57Bl/6 mice with CCl₄-or zymosan-induced hepatitis. Feeding a high-cholesterol diet led to a sharp increase in collagen content in the liver tissue of animals with CCl₄-induced or zymosan-induced hepatitis. Atorvastatin and calcitriol produced less pronounced fibrogenic effects. Mevalonate partially prevented the development of cholesterol-induced fibrogenesis. High-cholesterol diet led to accumulation of oxysterols, cholesterol esters, and triglycerides and increased the expression of transforming growth factor-β₁ mRNA in liver tissue. Cholesterol-induced potentiation of the fibrogenic response is probably associated with transforming growth factor-β₁ induction due to accumulation of lipids and oxysterols in the liver. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 145, No. 6, pp. 638–641, June, 2008