Rat HMGCoA reductase activation in thioacetamide-induced liver injury is related to an increased reactive oxygen species content

Background/Aims: In thioacetamide-induced liver injury a modification of isoprenoid content and an increase of reactive oxygen species has been described. We have examined how reactive oxygen species influence the 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate limiting enzyme of the isoprenoid biosynthetic pathway, to verify if changes of that enzyme activity are involved in the changed lipid composition of the liver. Methods: In chronic and acute thioacetamide-treated rat liver we measured the reactive oxygen species content, the activation state and K-M, the level and degradation rate of the hepatic reductase, its short term regulatory enzymes and the liver lipid profile. Results: In thioacetamide-treated rat liver, the reactive oxygen species content is high and the reductase is fully activated with no modifications in its K-M and its short term regulatory enzymes. The reductase level is reduced in chronic thioacetamide treated rats and its degradation rate is altered. Conclusions: The data show a relationship between reactive oxygen species production and altered 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. It is suggested that reducing the levels of reactive oxygen species may improve the altered lipid profile found in liver injury. (C) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.