The natural triterpenoid miliaсin prevents methotrexate-induced oxidative stress and normalizes the expression of genes encoding the cytochrome P-450 2E1 isoform and glutathione reductase in the liver

Abstract

We studied the role of the natural triterpenoid miliacin (3-β-метокси-Δ¹⁸-oleanene) in the regulation of oxidative stress in the liver of (СВАхС₅7В1₆)F₁ mice exposed to methotrexate. Miliacin attenuated methotrexate-induced lipid peroxidation as determined by an attenuation of thiobarbituric acid-reacting products in the liver. Furthermore, miliacin normalized the expression of genes encoding the 2e1 isoform of cytochrome Р-450 and glutathione reductase that were dramatically dysregulated by methotrexate. These results established the role of miliacin in modulation of redox genes, thereby providing evidence for a new mechanism of organ protection by this triterpenoid.