Toxicity of aromatic disulphides. I. Generation of superoxide radical and hydrogen peroxide by aromatic disulphides in vitro.
The aromatic thiol, thiophenol, is readily autoxidized at neutral pH in a reaction which generates superoxide radical and hydrogen peroxide. The oxidation product, diphenyl disulphide, may be reduced back to thiophenol by glutathione and in the presence of an excess of the latter thiol a reduction/autoxidation cycle for generation of 'active oxygen' species is established. The autoxidation reaction is strongly catalysed by haematin; haemoglobin is also an effective mediator of 'active oxygen' generation from the diphenyl disulphide/glutathione couple, being oxidized to methaemoglobin in the process. Certain derivatives of diphenyl disulphide also generate superoxide radical and hydrogen peroxide in the presence of glutathione, although the rate of the reaction is strongly influenced by the nature of the substituent groups. Among the ring-substituted derivatives of diphenyl disulphide investigated, the rate of 'active oxygen' production decreased in the order 4-amino greater than 2-amino greater than 4-methyl greater than unsubstituted greater than 4-nitro greater than 2-carboxyl; little reaction was detected with the homologous compound, dibenzyl disulphide.
D000818:Animals; D002374:Catalase / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D004220:Disulfides / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D066298:In Vitro Techniques; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010636:Phenols / Q000378:metabolism*; D051381:Rats; D013438:Sulfhydryl Compounds; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides; D013997:Time Factors; D014969:Xanthine Oxidase / Q000378:metabolism
D004220:Disulfides; D006454:Hemoglobins; D010636:Phenols; D013438:Sulfhydryl Compounds; D013481:Superoxides; D009249:NADP; C042983:thiophenol; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D005978:Glutathione