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Bilirubin oxidation products (BOXes) are produced by biochemical oxidation involving free peroxynitrite
Author(s) -
Wurster William L.,
Loftspring M.,
PyneGeithman G. J.,
Clark J. F.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.758.16
Subject(s) - peroxynitrite , chemistry , in vivo , bilirubin , kinetics , biochemistry , medicine , superoxide , enzyme , physics , microbiology and biotechnology , quantum mechanics , biology
Bilirubin oxidation products (BOXes), 1‐(1,5‐dihydropyrrole‐2‐ylidene)acetamide are vasoactive molecules with clinical importance. They are found in the cerebrospinal fluid of patients who have had hemorrhagic strokes. These compounds exhibit biological activity. We report here the production of BOXes via oxidation of unconjugated bilirubin (UBR) by peroxynitrite (PN) under conditions approximating in vivo conditions. Using a mixture of PN, buffer, UBR and O 2 we have generated BOXes, confirmed by UV/Vis consistent with known BOXes mixtures, and by HPLC‐MS. The oxidation kinetics is rapid at pH 7.5. Simple agonists and antagonists of the reaction exist. This is the second report of BOXes production using a well‐defined biological reaction. Considering the complexity of the process of maintaining vascular tone, it is not surprising that multiple routes to vasospastic compounds may exist. Following subarachnoid hemorrhage the amounts of UBR in the spinal fluid and chemical species, such as PN, created by oxidative stress are undoubtedly present. The oxidation of UBR to yield bioactive molecules, such as BOXes, is an important discovery, which expands the role of UBR in pathological processes. Therefore, in vitro production of BOXes could imply a specific in vivo therapeutic target for preventing BOXes production and thereby treating or preventing cerebral vasospasm. NIH: NS050569.