Effect of arsenical drugs on glutathione metabolism of Litomosoides carinii.
Despite centuries of therapeutic use, the mechanism of action of arsenicals against various diseases remains unknown. Because of the known inhibition of sulfhydryl-containing enzymes by arsenicals, we investigated the possibility that the anti-filarial effects of arsenical drugs might be exerted specifically through impairment of parasite thiol metabolism. We find: (1) arsenicals readily inhibit glutathione reductase of Litomosoides carinii but have little effect upon mammalian enzyme. (2) Administration of Melarsen B to filaria-infected gerbils causes decreases in filarial - but not host - glutathione reductase and reduced glutathione. (3) Such in vivo treatment does not, however, acutely affect parasite energy (ATP) metabolism. These results support the proposition that arsenicals may act through preferential interference with parasite thiol metabolism. The much greater susceptibility of parasite glutathione reductase to inhibition by arsenicals suggests that this enzyme may be a useful point of attack for new drugs.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001152:Arsenicals / Q000494:pharmacology*; D004912:Erythrocytes / Q000469:parasitology; D005370:Filarioidea / Q000187:drug effects* / Q000378:metabolism; D005849:Gerbillinae; D005978:Glutathione / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism; D013997:Time Factors
D001152:Arsenicals; D000255:Adenosine Triphosphate; D005980:Glutathione Reductase; D005978:Glutathione