Photocatalytic actions of the pesticide metabolite 2-hydroxyquinoxaline: destruction of antioxidant vitamins and biogenic amines - implications of organic redox cycling.
Toxicity of the pesticide quinalphos may comprise secondary, delayed effects by its main metabolite 2-hydroxyquinoxaline (HQO). We demonstrate that HQO can destroy photocatalytically vitamins C and E, catecholamines, serotonin, melatonin, the melatonin metabolite AMK (N(1)-acetyl-5-methoxykynuramine), and unsubstituted and substituted anthranilic acids when exposed to visible light. In order to avoid HQO-independent ascorbate oxidation by light and to exclude actions by hydroxyl radicals, experiments on this vitamin were carried out in ethanolic solutions. Other substances tested (vitamin E, melatonin, anthranilic acids) were also photocatalytically destroyed by HQO in ethanol. After product analyses had indicated that HQO was not, or only poorly, degraded in the light, despite its catalytic action on other compounds, we followed directly the time course of HQO and ascorbate concentrations in ethanol. While ascorbate was largely destroyed, no change in HQO was demonstrable within 2 h of incubation. Destruction was not prevented by the singlet oxygen quencher DABCO. Obviously, HQO is capable of undergoing a process of organic redox cycling, perhaps via an intermediate quinoxaline-2-oxyl radical. Health problems from HQO intoxication may not only arise from the loss of valuable biomolecules, such as antioxidant vitamins and biogenic amines, but also from the formation of potentially toxic products. Dimerization and oligomerization are involved in several oxidation processes catalyzed by HQO, especially in the indoleamines, in dopamine, and presumably also in vitamin E. Melatonin oxidation by HQO did not only lead to the well-known - and usually protective - metabolite AFMK (N(1)-acetyl-N(2)-formyl-5-methoxykynuramine), but also to a high number of additional products, among them dimers and trimers. DABCO did not prevent melatonin destruction, but changed the spectrum of products. Serotonin was preferentially converted to a dimer, which can further oligomerize. Several indole dimers are known to be highly neurotoxic, as well as oxidation products formed from catecholamines via the adrenochrome/noradrenochrome pathway. Destruction of melatonin may cause deficiencies in circadian physiology, in immune functions and in antioxidative protection.
Behrends
Andreas
A
Institut für Zoologie, Anthropologie und Entwicklungsbiologie, Universität Göttingen, Göttingen, Germany.
Hardeland
Rüdiger
R
Ness
Heiko
H
Grube
Sascha
S
Poeggeler
Burkhard
B
Haldar
Chandana
C
D000588:Amines / Q000737:chemistry; D000975:Antioxidants / Q000737:chemistry; D001205:Ascorbic Acid / Q000737:chemistry / Q000378:metabolism; D002384:Catalysis; D002395:Catecholamines / Q000378:metabolism; D019281:Dimerization; D004298:Dopamine / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000737:chemistry; D007735:Kynuramine / Q000031:analogs & derivatives* / Q000737:chemistry; D008027:Light; D008550:Melatonin / Q000737:chemistry / Q000378:metabolism; D008956:Models, Chemical; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D011810:Quinoxalines / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013053:Spectrophotometry; D013997:Time Factors; D014466:Ultraviolet Rays; D014810:Vitamin E / Q000378:metabolism; D014815:Vitamins / Q000737:chemistry
D000588:Amines; D000975:Antioxidants; D002395:Catecholamines; D016166:Free Radical Scavengers; D016877:Oxidants; D010879:Piperazines; D011810:Quinoxalines; D014815:Vitamins; C098565:2-hydroxyquinoxaline; D014810:Vitamin E; D012701:Serotonin; D007735:Kynuramine; D000431:Ethanol; C041550:N-acetyl-N-formyl-5-methoxykynurenamine; D008550:Melatonin; D001205:Ascorbic Acid; D010100:Oxygen; D004298:Dopamine; C007306:triethylenediamine