dc.creatorDiaz, Edith Graciela
dc.creatorMontalto, Maria
dc.creatorCastro, Jose Alberto
dc.date.accessioned2019-09-02T20:33:55Z
dc.date.accessioned2022-10-15T01:18:21Z
dc.date.available2019-09-02T20:33:55Z
dc.date.available2022-10-15T01:18:21Z
dc.date.created2019-09-02T20:33:55Z
dc.date.issued2004-05
dc.identifierDiaz, Edith Graciela; Montalto, Maria; Castro, Jose Alberto; Reactions of Nifurtimox with critical sulfhydryl-containing biomolecules: Their potential toxicology relevance; John Wiley & Sons Ltd; Journal of Applied Toxicology; 24; 3; 5-2004; 189-195
dc.identifier0260-437X
dc.identifierhttp://hdl.handle.net/11336/82773
dc.identifierCONICET Digital
dc.identifierCONICET
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/4329108
dc.description.abstractNifurtimox (Nfx) is a drug used in the treatment of Chagas' disease, an endemic parasitic disease from Latin American countries. It produces undesirable side-effects in patients, frequently forcing the treatment to be stopped. Its toxic mechanism is not fully understood. In this work we describe purely chemical reactions of Nfx with relevant cellular sulfhydryl (SH) compounds. The compounds tested were glutathione (GSH), cysteine (RSH), lipoic acid (LA) and coenzyme A (CoA). All reacted with Nfx to give nitrite (NO2-). The relative reaction rates were CoA>LA>GSH>RSH. In studies with GSH and RSH the formation of nitrite was accompanied by decreases in Nfx concentration and increases in the formation of a reaction product revealed by HPLC. We failed to show the presence of liver cytosolic GST (GSH transferase activity)-mediated formation of NO2 - from Nfx. These NO2--releasing processes occurred under in vivo conditions in Nfx-treated Sprague-Dawley male rats (240-260 g body weight) at a dose of 100 mg Nfx kg-1 p.o. In urine samples NO2- excretion was accompanied by unchanged drug and two unidentified more polar metabolites detectable by HPLC. The Nfx reactions with critical SH from molecules such as GSH, RSH, LA and CoA, and potentially others containing SH residues (e.g. enzymes or structural proteins), might have toxicological relevance not only for the Nfx side-effects but also for the chemotherapeutic effects on Trypanosoma cruzi. In addition, Nfx reactions with GSH might be crucial in Nfx detoxification.
dc.languageeng
dc.publisherJohn Wiley & Sons Ltd
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/jat.970
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1002/jat.970
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectADVERSE EFFECTS
dc.subjectCHAGAS'S DISEASE
dc.subjectCHEMOTHERAPEUTIC EFFECTS
dc.subjectNIFURTIMOX
dc.subjectNITRITE ANION
dc.subjectSULFHYDRYL COMPOUNDS
dc.titleReactions of Nifurtimox with critical sulfhydryl-containing biomolecules: Their potential toxicology relevance
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:ar-repo/semantics/artículo
dc.typeinfo:eu-repo/semantics/publishedVersion


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