Disease relevance of CCRIS 3473

• Urinary 6-hydroxymelatonin excretion in patients with orthostatic hypotension [1].
• Twenty-four hour urinary excretion of 6-hydroxymelatonin sulfate in Down syndrome subjects [2].
• The mutagenicity of melatonin and its major metabolite 6-hydroxymelatonin were evaluated using the Ames test and three strains of Salmonella typhimurium--TA 97, TA 98, and TA 100 [3].
• Inhibition of human chorionic gonadotrophin-induced hypertrophy of the ovaries and uterus in immature mice by some pineal indoles, 6-hydroxymelatonin and arginine vasotocin [4].
• The protective effect of melatonin, 6-hydroxymelatonin and N-acetylserotonin against alpha-naphthylisothiocyanate (ANIT)-induced liver injury was investigated and compared in rats injected once with the hepatotoxicant (75 mg/kg body weight) [5].

Psychiatry related information on CCRIS 3473

• Levels of the melatonin metabolite, 6-hydroxymelatonin sulfate, were measured in overnight urine from 31 prepubertal children with major depressive disorder and 15 normal control children with very low family loading for affective disorder [6].
• Urinary 6-hydroxymelatonin sulfate excretion in intellectually disabled subjects with sleep disorders and multiple medications: validation of measurements in urine extracted from diapers [7].

High impact information on CCRIS 3473

• BACKGROUND: Melatonin is a hormone that is metabolized by cytochrome P450 (CYP) 1A2 to its main primary metabolite 6-hydroxymelatonin [8].
• Melatonin and conjugated 6-hydroxymelatonin were analyzed by liquid chromatography-mass spectrometry in blood samples taken between 0.5 and 6.5 hours after drug intake [8].
• To determine whether melatonin pharmacokinetics change during puberty, we infused melatonin iv in 9 prepubertal, 8 pubertal, and 16 adult subjects and measured melatonin in serum and saliva, and 6-hydroxymelatonin sulfate in urine [9].
• The present study investigated whether 6-hydroxymelatonin (6-OHM) can reduce Fe2+-induced lipid peroxidation and necrotic cell damage in the rat hippocampus in vivo [10].
• Melatonin production during childhood and adolescence: a longitudinal study on the excretion of urinary 6-hydroxymelatonin sulfate [11].

Biological context of CCRIS 3473

• It is noteworthy that 6-hydroxymelatonin can efficiently induce DNA damage via non-o-quinone type of redox cycle [12].
• Cytochrome P450 reductase efficiently enhanced 6-hydroxymelatonin-induced oxidative DNA damage and oxygen consumption, suggesting the formation of redox cycle [12].
• Melatonin and 6-hydroxymelatonin were potent displacers of 2-[125I]iodomelatonin binding in the AP (IC50 20 and 500 pM, respectively) while N-acetylserotonin exhibited only a modest potency (IC50 25 nM) [13].
• A systematic study of cross-reactions with 14 compounds (indole, aromatic and imidazole derivatives) showed that the antibody had a high specificity for melatonin, low reactivities with 6-hydroxymelatonin and N-acetylserotonin and no detectable reactivity with 12 other derivatives [14].
• The present study therefore investigates the possible manner in which 6-hydroxymelatonin protects against oxidative stress induced by cyanide in rat brain homogenates [15].

Anatomical context of CCRIS 3473

• Understanding 6-hydroxymelatonin (6HM) sulfation is deemed important to explaining normal and oncostatic actions of the pineal gland [16].
• The 6-hydroxymelatonin-induced 8-oxodG formation in HL-60 cells significantly decreased by the addition of bathocuproine or o-phenanthroline [12].
• Furthermore, 6-hydroxymelatonin significantly increased the formation of 8-oxodG in human leukemia cell line HL-60 but not in HP100, a hydrogen peroxide (H2O2)-resistant cell line derived from HL-60 [12].
• Formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a characteristic oxidative DNA lesion, in calf thymus DNA was significantly increased by 6-hydroxymelatonin in the presence of Cu(II) [12].
• 6-hydroxymelatonin, although able to provide partial protection against the ANIT-induced hepatic injury, probably through its antioxidant properties by mechanisms that are unclear, was unable to reduce neutrophil infiltration [5].

Associations of CCRIS 3473 with other chemical compounds

• Melatonin was found to be almost exclusively metabolized by CYP1A2 to 6-hydroxymelatonin and N-acetylserotonin with a minimal contribution of CYP2C19 [17].
• Neither 6-hydroxymelatonin nor serotonin affected MBH cyclo-oxygenase pathway in vitro [18].
• They showed high affinities toward p-nitrophenol and 6-hydroxymelatonin as found in human ST1A3 [19].
• Liver homogenates were used to monitor the in vitro conversion of melatonin or 6-hydroxymelatonin to 6-sulfatoxymelatonin [20].
• Using a new radioimmunoassay for 6-hydroxymelatonin sulphate (aMT6s), the major melatonin metabolite, we have shown that the urinary aMT6s rhythm is closely correlated to that of melatonin in plasma and is completely suppressed by an acute dose of atenolol (100 mg per os), a peripheral beta-adrenergic antagonist [21].

Gene context of CCRIS 3473

• 6-Hydroxymelatonin was glucuronidated largely by UGT1A9 and UGT1A10 but not at all by UGT1A6 [22].
• The subcutaneous implantation of either melatonin or 6-hydroxymelatonin (1 mg/wk in beeswax) prevented the atrophy of the reproductive organs and the decrease in the stores of pituitary prolactin [23].

Analytical, diagnostic and therapeutic context of CCRIS 3473

• In our HPLC program for indoles the cyclic 2-hydroxymelatonin eluted at 25 min, separately from synthetic indoles, between 6-hydroxymelatonin (19 min) and melatonin (35 min) [24].
• To purify solubilized receptors, a novel affinity chromatography resin was developed by coupling 6-hydroxymelatonin with Epoxy-activated Sepharose 6B [25].
• The effect of presynaptic catecholamine depletion on 6-hydroxymelatonin sulfate: a double blind study of alpha-methyl-para-tyrosine [26].
• Comparison of the new RIA using 125I-aMT6s with the RIA using 3H-aMT6s label gave good correlation, as did comparison with a gas chromatography mass spectroscopy (GCMS) for total free and conjugated 6-hydroxymelatonin [27].
• Electrical stimulation of the PVN during the early lights-on period significantly elevated urinary 6-hydroxymelatonin content to nearly 50% of night levels; stimulation during the lights-off period did not produce significant changes [28].

References