Intracellular and extracellular redox environments surrounding redox-sensitive contrast agents under oxidative Atmosphere.

Abstract:

:In vivo redox reactions of nitroxyl contrast agents in bile and blood under an oxidative atmosphere were investigated using normal healthy Wistar rats. Differences in intracellular and extracellular volumes in redox environments are discussed. Pharmacokinetic profiles of two nitroxyl contrast agents, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl (carbamoyl-PROXYL), 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL), in bile and blood were monitored by an electron paramagnetic resonance spectrometer when the rat was breathing 100% O(2) or was subcutaneously administrated 0.2 mmol/kg body weight of ferric citrate. Re-oxidation of hydroxylamines to nitroxyl radicals was caused in bile under 100% O(2) breathing, but not in blood. The administration of ferric citrate caused marked re-oxidation in bile, but a slight reduction in blood. Tissue H(2)O(2) level may partly play a role in the intracellular re-oxidation process. Tissue Fe(3+) concentration can work more effectively for the intracellular re-oxidation of hydroxylamines. The intracellular environment is susceptible to oxidation compared with the extracellular environment under conditions such as 100% O(2) breathing or iron overload.

journal_name

Biol Pharm Bull

authors

Okajo A,Ui I,Manda S,Nakanishi I,Matsumoto K,Anzai K,Endo K

doi

10.1248/bpb.32.535

subject

Has Abstract

pub_date

2009-04-01 00:00:00

pages

535-41

issue

4

eissn

0918-6158

issn

1347-5215

pii

JST.JSTAGE/bpb/32.535

journal_volume

32

pub_type

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