EFFECTS OF THE ANTIOXIDANT (6,7-DIHYDROXYCOUMARIN) ESCULETIN ON THE GLUTATHIONE SYSTEM AND LIPID-PEROXIDATION IN MICE

The attempt to retard senescence by environmental manipulation include s the use of nutrients or drugs that decrease the oxidative damage to tissues associated with aging. The effects of esculetin treatment (25 mg/kg, orally for 30 days), a phenolic antioxidant compound, on the gl utathione system and lipid peroxidation were examined in liver superna tants from male C57BL/6J mice. The effects of esculetin were compared to treatment with 3,5-di-terc-butyl-4-hydroxytoluene (BHT), a well-kno wn synthetic phenolic antioxidant. Reduced glutathione (GSH) concentra tion in liver supernatants was only increased significantly in esculet in-treated mice compared to control animals, whereas the concentration of oxidized glutathione (GSSG) was significantly decreased by BHT tre atment compared to the control group. The GSSG/GSH ratio was significa ntly lower in esculetin and BHT groups than in the control group. The decrease in this ratio was greater in BHT-treated mice than in esculet in-treated mice. Increases in glutathione reductase (GR) activity were observed with both treatments, although BHT resulted in a superior in duction of this activity compared to esculetin. The extent of decline in the GSSG/GSH ratio was correlated with the increase in GR activity. The formation of thiobarbituric acid-reactive substances (TBARs), an index of stress, was lower following treatment with esculetin and BHT compared to control mice (although not significant). This index was ve ry similar for both treatments. Based on the level of TBARs obtained i n this study, the accumulation of lipid peroxides declines when the GS H levels are enhanced or GSSG levels are decreased. Finally, we found similar antioxidant effects in vivo with esculetin and BHT treatments and a decrease in the oxidative damage evaluated. The enhancement of g lutathione status following esculetin treatment could be a possible de fense strategy for the organism under 'stress conditions' and may be r elated to the delay of age-dependent degenerative disorders.