Effect of sesquiterpene lactones on antioxidant enzymes and some drug-metabolizing enzymes in rat liver and kidney.

Previously we have reported that several sesquiterpene lactones isolated from Helenium aromaticum and Telekia speciosa showed pro-oxidative properties and caused glutathione level depletion in rat liver in vivo. In the present study we examined the in vivo effect of these lactones on antioxidant enzyme systems and some drug metabolizing enzymes in the liver and the kidney of rats. We found that the majority of the compounds increased the hepatic activity of glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT), but superoxide dismutase (SOD) activity was distinctly lowered by five lactones. A few of the compounds tested caused a decrease in the hepatic cytochrome P450 content and reduced the activity of NADPH-cytochrome P450 reductase, aminopyrine demethylase, aniline hydroxylase and glutathione-S-transferase. Results for the kidney showed fewer changes in activities of both classes of enzymes when compared to the liver. Not all lactones affected the enzymes under test, the most active were: linifolin, helenalin, mexicanin 1 and telekin. 6 alpha-Hydroxy-2,3-dihydroaromaticin behaved differently towards monooxygenases since it induced the activity of aminopyrine demethylase and aniline hydroxylase.

Effect of several sesquiterpene lactones on lipid peroxidation and glutathione level.

Seven sesquiterpene lactones isolated from Helenium aromaticum: helenalin, mexicanin I, linifolin A, geigerinin, and from Telekia speciosa: 6 alpha-hydroxy-2,3-dihydroaromaticin, asperilin, telekin have been tested for their hydroxyl radical scavenging activity and effect on lipid peroxidation. All compounds were found to be potent hydroxyl radical scavengers but did not affect lipid peroxidation in vitro. In vivo they exerted pro-oxidative properties and caused glutathione level depletion and elevation in glutathione peroxidase activity.