GLUTATHIONE AND N-ACETYLCYSTEINE PROTECTION AGAINST ACETALDEHYDE EMBRYOTOXICITY IN RAT EMBRYOS DEVELOPING IN-VITRO

Previous in vitro studies demonstrated that acetaldehyde (ACHO) is abl e to produce specific morphological alterations related to the foetal alcohol syndrome. Intracellular reduced glutathione (GSH) has been sho wn to modulate the embryotoxicity elicited by various chemicals in viv o and in vitro. The present study evaluates the role played by endogen ous and exogenous GSH and its precursor N-acetylcysteine (NAG) on the embryotoxicity induced by ACHO using the rat whole embryo culture syst em. In the first experiment embryos at gestation day (GD) 9.5 were cul tured in rat serum medium for 18 hr in the presence of 1 mM L-buthioni ne-S,R-solfoximine (BSO), a specific inhibitor of GSH synthesis. Follo wing pretreatment, conceptuses were cultured for a further 30 hr in th e presence of 30 mu g ACHO/ml. Pretreatment with BSO significantly enh anced the embryotoxic effects of ACHO and markedly reduced the GSH lev el only in the yolk sac. In the second experiment GSH or NAC (8 mu m) were added to the medium by two different procedures in an attempt to reduce ACHO-induced embryotoxicity. In one case the embryos were expos ed to ACHO for 8 hr and then transferred to media containing NAC or GS H for the remaining time of culture (22 hr); in another, the embryos w ere maintained for the entire culture period (30 hr) in a medium conta ining ACHO plus NAC or GSH. Only in the first case did exposure to NAC significantly reduce the frequency of abnormal embryos; in the second case the concurrent exposure to ACHO and thiols only marginally reduc ed ACHO-induced effects. Significant variations in the GSH content wer e recorded only at the level of the yolk sac. This result suggests tha t the yolk sac GSH can play a major role in the protection of the embr yo against the toxic effects produced by xenobiotics.