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 includes 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 glutathione system and lipid peroxidation were examined in liver supernatants from male C57BL/6J mice. The effects of esculetin were compared to treatment with 3,5-di-terc-butyl-4-hydroxytoluene (BHT), a well-known synthetic phenolic antioxidant. Reduced glutathione (GSH) concentration in liver supernatants was only increased significantly in esculetin-treated mice compared to control animals, whereas the concentration of oxidized glutathione (GSSG) was significantly decreased by BHT treatment compared to the control group. The GSSG/GSH ratio was significantly lower in esculetin and BHT groups than in the control group. The decrease in this ratio was greater in BHT-treated mice than in esculetin-treated mice. Increases in glutathione reductase (GR) activity were observed with both treatments, although BHT resulted in a superior induction 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 very similar for both treatments. Based on the level of TBARs obtained in this study, the accumulation of lipid peroxides declines when the GSH 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 glutathione status following esculetin treatment could be a possible defense strategy for the organism under 'stress conditions' and may be related to the delay of age-dependent degenerative disorders.