Different Doxorubicin Formulations Affect Plasma 4-Hydroxy-2-Nonenal and Gene Expression of Aldehyde Dehydrogenase 3A1 and Thioredoxin Reductase 2 in Rat
|Článek v odborném periodiku
|Časopis / Zdroj
|Fakulta / Pracoviště MU
|Doxorubicin; Drug nanotransporters; Oxidative stress; 4-hydroxy-2-nonenal; Thioredoxin reductase 2; Aldehyde dehydrogenase 3A1
|Increased oxidative stress is indisputably an important mechanism of doxorubicin side effects, especially its cardiotoxicity. To prevent Impairment of non-tumnrous tissue and to Improve the specificity in targeting the tumor tissue, new drug nanotransporters are developed. In many cases predinical therapeutic advantage has been shown when compared with the administration of conventional drug solution. Three forms of doxorubicin - conventional (DOX), encapsulated In liposomes (lipoDOX) and in apoferritin (apoDQX) were applied to Wistar rats. After 24 h exposition, the plasma level of 4-hydroxy-2-nonenal (4-HNE) as a marker of lipoperoxidalion and tissue gene expression of thioredoxln reductase 2 (TXNRDZ} and aldehyde dehydrogenase 3A1 (ALDH3AI) as an important part of antioxidative system were determined. Only conventional DOX significantly increases the level of 4-HNE; encapsulated forms on the other hand show significant decrease in plasma levels of 4-HNE In comparison with DOX. They also cause significant decrease In gene expression of ALDH3A1 and TXNRD2 In liver as a main detoxification organ, and a mild Influence on the expression of these enzymes in left heart ventride as a potential target of toxiclty. Thus, 4-HNE seems to be a good potential biomarker of oxidative stress induced by various forms of doxorubicin.