ABSTRACT
We studied the role of the natural triterpenoid miliacin (3-3-methoxy-Al8-oleanene) in the regulation of oxidative stress in the liver of (CBAxC57B1(6))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 P-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.
Subject(s)
Cytochrome P-450 CYP2E1/metabolism , Glutathione Reductase/metabolism , Liver/enzymology , Oxidative Stress/drug effects , Triterpenes/pharmacology , Animals , Cytochrome P-450 CYP2E1/genetics , Gene Expression/drug effects , Glutathione Reductase/genetics , Isoenzymes/genetics , Isoenzymes/metabolism , Lipid Peroxidation , Male , Methotrexate/toxicity , MiceABSTRACT
Biodegradable polylactide microparticles with encapsulated cytotoxic protein viscumin were obtained via the ultrasound-assisted supercritical fluid technique. The size of the microparticles was 10-50 µM, as shown by electron microscopy. The time course of viscumin release from microparticles was studied using an immunoenzyme test system with anti-viscumin monoclonal antibodies. It was found that 99.91% of the cytotoxic protein was incorporated into polymer microparticles. Only 0.08% of the initially encapsulated viscumin was released from the microparticles following incubation for 120 h in a phosphate-buffered saline at neutral pH. Importantly, the method of ultrasonic dry supercritical fluid encapsulation failed to alter both the cytotoxic potency and the immunochemical properties of the encapsulated viscumin. Thus, this procedure can be used to generate biodegradable polylactide microparticles with encapsulated bioactive substances.