Beta-carotene cleavage products after oxidation mediated by hypochlorous acid--a model for neutrophil-derived degradation.
After beta-carotene failed in certain clinical efficacy trials, there is evidence that the carotenoid might even be harmful, especially to smokers, when given in high dosages. These negative effects might be mediated in part also by carotenoid cleavage products (CPs) having a high reactivity towards biomolecules. The authors postulate that in certain tissues oxidative, nonenzymatic cleavage of carotenoids is carried out primarily by oxidants liberated by polymorphonuclear leukocytes (PML). In this study, we show that beta-carotene is degraded by stimulated PML in vitro. This gives the pathophysiological meaning to our further experiments in which beta-carotene degradation by hypochlorous acid and consecutive CP formation were investigated. While formation of apo-carotenals under these conditions has been studied before, this was not the case for short chain products. Performing gas chromatography mass spectrometry, we were able to identify for the first time 5,6-epoxi-beta-ionone, ionene, beta-cyclocitral, beta-ionone, dihydroactinidiolide, and 4-oxo-beta-ionone as CPs formed after degradation of beta-carotene mediated by hypochlorous acid. Our findings may be of biological relevance because beta-carotene CPs are highly reactive and, therefore, potentially toxic.
Sommerburg
Olaf
O
Department of Pediatrics, University of Ulm, Ulm, Germany. olaf.sommerburg@t-online.de
Langhans
Claus-Dieter
CD
Arnhold
Jürgen
J
Leichsenring
Michael
M
Salerno
Costantino
C
Crifò
Carlo
C
Hoffmann
Georg F
GF
Debatin
Klaus-Michael
KM
Siems
Werner G
WG
D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006997:Hypochlorous Acid / Q000378:metabolism / Q000494:pharmacology*; D000432:Methanol / Q000737:chemistry; D008956:Models, Chemical; D009504:Neutrophils / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D019207:beta Carotene / Q000378:metabolism*
D005609:Free Radicals; D019207:beta Carotene; D006997:Hypochlorous Acid; D010100:Oxygen; D000432:Methanol