ANETHOLE DITHIOLETHIONE PREVENTS OXIDATIVE DAMAGE IN GLUTATHIONE-DEPLETED ASTROCYTES

Astrocytes protect neurons against reactive oxygen species such as hyd rogen peroxide, a capacity which reportedly is abolished following los s of the antioxidant glutathione. Anethole dithiolethione, a sulfur-co ntaining compound which is used in humans, is known to increase cellul ar glutathione levels and thought thereby to protect against oxidative damage. In the present study we found that anethole dithiolethione in creased the glutathione content of cultured rat striatal astrocytes. T his effect was abolished by coincubation with the glutathione synthesi s inhibitor buthionine sulfoximine. Nevertheless, in the presence of b uthionine sulfoximine, despite the lack of an increase in the lowered glutathione level, anethole dithiolethione fully protected the astrocy tes against the enhanced toxicity of hydrogen peroxide. Thus, apparent ly other mechanisms than stimulation of glutathione synthesis are invo lved in the compound's protective action in astrocytes. Considering th e occurrence of lowered glutathione levels in neurodegenerative syndro mes, we conclude that further evaluation of the therapeutic potential of anethole dithiolethione is warranted. (C) 1997 Elsevier Science B.V .