{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T15:24:00Z","timestamp":1778167440020,"version":"3.51.4"},"reference-count":0,"publisher":"Cambridge University Press (CUP)","issue":"6","license":[{"start":{"date-parts":[[1999,6,1]],"date-time":"1999-06-01T00:00:00Z","timestamp":928195200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Parasitology"],"published-print":{"date-parts":[[1999,6]]},"abstract":"<jats:p>The aim of this investigation was to examine whether macrophage and <jats:italic>Leishmania major<\/jats:italic> glutathione were involved in \neither host or parasite protection against NO cytotoxicity. Buthionine sulfoximine (BSO), an inhibitor of \u03b3-glutamyl-cysteine synthase, caused a complete and irreversible depletion of macrophage glutathione, but only a 20% and reversible \ndecrease in <jats:italic>L. major<\/jats:italic> glutathione. Glutathione-depleted macrophages, when activated with IFN-\u03b3\/LPS, released less than \n60% of the NO produced by untreated macrophages, resulting in a corresponding decrease in their leishmanicidal activity. \nBSO-treated macrophages were more susceptible to the cytotoxic effects of the NO donor SNAP. Treatment of macrophages \nwith 1,3-<jats:italic>bis<\/jats:italic>(chloroethyl)-1-nitrosourea (BCNU), an inhibitor of glutathione reductase and trypanothione \nreductase or with Br-Octane, a glutathione-S-transferase substrate, resulted in a transient decrease in glutathione levels \nand did not increase the susceptibility of the macrophages to SNAP. Treatment of the promastigote forms of <jats:italic>L. major<\/jats:italic> \nwith BCNU resulted in an 80% decrease in total glutathione concentration with no concomitant change in viability. \nHowever, this treatment rendered the parasites more susceptible to SNAP. Finally, macrophage glutathione protected the \ninternalized <jats:italic>L. major<\/jats:italic> from SNAP. Overall, these results demonstrate that glutathione is an essential protective component \nagainst NO cytotoxicity on both macrophages and parasites.<\/jats:p>","DOI":"10.1017\/s0031182099004278","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:30:22Z","timestamp":1027762222000},"page":"559-566","source":"Crossref","is-referenced-by-count":33,"title":["Glutathione protects macrophages and <i>Leishmania major<\/i> \nagainst nitric oxide-mediated cytotoxicity"],"prefix":"10.1017","volume":"118","author":[{"given":"P. R. T.","family":"ROM\u00c3O","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. G.","family":"FONSECA","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. S.","family":"HOTHERSALL","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. A.","family":"NORONHA-DUTRA","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. H.","family":"FERREIRA","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F. Q.","family":"CUNHA","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[1999,6,1]]},"container-title":["Parasitology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0031182099004278","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,4,11]],"date-time":"2019-04-11T16:01:49Z","timestamp":1554998509000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0031182099004278\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,6]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1999,6]]}},"alternative-id":["S0031182099004278"],"URL":"https:\/\/doi.org\/10.1017\/s0031182099004278","relation":{},"ISSN":["0031-1820","1469-8161"],"issn-type":[{"value":"0031-1820","type":"print"},{"value":"1469-8161","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,6]]}}}