The effects of high-fat diet on the thiol disulfide homeostasis of rats were evaluated by activities of glutathione redox system functioning in the blood and liver. A short-term (30 days) high-fat diet inhibited activities of glutathione-dependent enzymes. High-fat loading for 90 days promoted the development of a compensatory response of the glutathione redox system and restoration of the thiol disulfide homeostasis. The compensatory processes in the glutathione system failed on day 180 of alimentary loading because of redox imbalance in the thiol disulfide metabolism.

We studied phospholipid composition of erythrocytes and the state of the glutathione redox system in rats during adaptation to cholesterol load for 180 days. The adaptive response is formed during the period from day 30 to day 90 of cholesterol load and is associated with increased relative content of phosphatidylethanolamine and phosphatidylinositol, activation of glutathione redox system enzymes (glutathione reductase and glutathione peroxidase), and enhanced production of glutathione.

We studied heme oxygenase-1 expression in rat liver during the development of nonalcoholic steatohepatitis simulated by feeding high-fat ration for 30, 90, and 180 days. Increased number of hepatocytes synthesizing heme oxygenase-1 was demonstrated at all stages of pathology development. Herewith, the intensity of enzyme expression by individual cells was reduced on experimental day 180 during the development of liver fibrosis.

The new model of nonalcoholic steatohepatitis in rats is based on alimentary effects of hypercaloric diet including much cholesterol and beef fat. This model reproduces structural and functional disorders in the liver, including hepatocyte fatty degeneration, parenchymatous necrosis and fibrosis paralleled by dyslipidemia and is intended for studies of the mechanisms of formation, progress, and therapy of liver diseases of noninfectious origin.