{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T23:58:52Z","timestamp":1790985532131,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2002,5,8]],"date-time":"2002-05-08T00:00:00Z","timestamp":1020816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2002,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Oxidative stress contributes to the development of early transplant failure. As nitric oxide synthases (NOS) can act as sources of superoxide, we investigated the effect of the NOS cofactor tetrahydrobiopterin (BH4) on oxyradical production and early rejection in a rat kidney transplantation model. Allograft transplantation (Brown Norway to Lewis) showed more renal superoxide production and monocyte infiltration when compared with isografts (Lewis to Lewis). Administration of the stable BH4 precursor sepiapterin had no effect on superoxide production in the isografts (51\u00b110 vs. 69\u00b117 cps\/10 mg protein), but led to a marked decrease in superoxide production in the allografts (116\u00b111 vs. 60\u00b16 cps\/10 mg protein;\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05) and was accompanied by a reduction in periarterial macrophage infiltration (3.3\u00b10.7 vs. 1.3\u00b10.3 cells\/vessel;\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05) and an increase in NO production (78\u00b122 vs. 173\u00b112 AU\/g kidney) (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.01). In vitro experiments confirm that iNOS can produce superoxide mainly from the heme domain, whereas BH4 administration can reverse this superoxide production in the presence of adequate anti\u2010oxidant defense. Our findings support the hypothesis that BH4 can be used to modulate the function of the inflammatory iNOS isoform and suggest a potential therapeutic role for sepiapterin in early allograft rejection.\n                  <\/jats:p>","DOI":"10.1096\/fj.01-0890fje","type":"journal-article","created":{"date-parts":[[2002,7,28]],"date-time":"2002-07-28T18:39:25Z","timestamp":1027881565000},"page":"1135-1137","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Anti\u2010inflammatory effects of tetrahydrobiopterin on early rejection in renal allografts: modulation of inducible nitric oxide synthase"],"prefix":"10.1096","volume":"16","author":[{"given":"Albert","family":"Huisman","sequence":"first","affiliation":[{"name":"Department of Vascular Medicine University Medical Center  Utrecht the Netherlands"},{"name":"Department of Clinical Chemistry University Medical Center  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Vos","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension University Medical Center  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernst E.","family":"Van Faassen","sequence":"additional","affiliation":[{"name":"Debye Institute Section Interface Physics Utrecht University  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaap A.","family":"Joles","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension University Medical Center  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann\u2010Josef","family":"Gr\u00f6ne","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Pathology German Cancer Institute  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Martasek","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Faculty of Medicine I Charles University  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton\u2010Jan","family":"Van Zonneveld","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine University Medical Center  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anatoly F.","family":"Vanin","sequence":"additional","affiliation":[{"name":"Institute of Chemical Physics Russian Academy of Sciences  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ton J.","family":"Rabelink","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine University Medical Center  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,5,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.14.5.815"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.13.11.1371"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.060002786.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198501173120305"},{"key":"e_1_2_7_6_1","doi-asserted-by":"crossref","DOI":"10.1016\/S0021-9258(19)51062-6","article-title":"Determination of the mechanism of free radical generation in human aortic endothelial cells exposed to anoxia and reoxygenation","volume":"269","author":"Zweier J. 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