Disease relevance of Adrenochrome

• We tested the in vivo activation of leukocytes by measuring plasma oxidation of adrenaline to adrenochrome in patients suffering from cerebral ischemia, cerebral hemorrhage, and transient ischemic attacks and in healthy subjects [1].
• RESULTS: Adrenochrome monoaminoguanidine methanesulfonate+cytochrome C augumented NK activity in KSN nude mice, protected potent NK cells in patients with lung cancer against RT and sensitized the human lung cancer xenografts to RT [2].
• It is suggested that sudden death due to arrhythmias in patients following the first attack of myocardial infarction of during other stressful situations may be linked to the formation of adrenochrome from abnormally high catecholamine levels in blood [3].
• Single intravenous injection of adrenochrome (10 to 50 mg/kg body weight), an oxidation product of catecholamines, has been shown to induce arrhythmias and cause death in anesthetized rats in a dose-dependent manner [3].
• Procaine, hypocalcemia, magnesium, fluoride, adrenochrome, and tetrodotoxin have been used to induce metabolic arrest of the heart and increase its tolerance to ischemia [4].

High impact information on Adrenochrome

• The autooxidation of epinephrine to adrenochrome is mediated by superoxide anions and inhibited by captopril, SQ 14,534, and zofenopril, with similar IC50 values of 8 to 10 microM, but not by enalaprilat or teprotide (IC50 greater than 1000 microM) [5].
• Homogenates of normal human granulocytes were found to catalyze the oxidation of epinephrine to adrenochrome [6].
• The oxidation of adrenaline to adrenochrome has been shown to reflect the activation of leukocytes in vivo [1].
• The oxidation product of adrenaline, adrenochrome, is less active as a substrate for GST M2-2, and more efficiently conjugated by GST M1-1 [7].
• The fallacy of using adrenochrome reaction for measurement of reactive oxygen species formed during cytochrome p450-mediated metabolism of xenobiotics [8].

Chemical compound and disease context of Adrenochrome

• Nuclear membranes from many tumors contain an unusual redox chain discovered originally in the Hepatoma 22a nuclear membranes which catalyzes superoxide dismutase-sensitive adrenaline oxidation to adrenochrome in the presence of either NADPH or NADH as electron donor, the reaction being inhibited by cyanide and azide [9].

Biological context of Adrenochrome

• Inhibition of kidney cortex gluconeogenesis by adrenochrome and indile 2-carboxylic acid [10].
• We have examined the effects of adrenochrome and other metabolites of epinephrine on the ultrastructure and contractile activity of isolated rat hearts perfused under conditions in which the heart rate and coronary flow were controlled [11].
• Sulfinpyrazone, which is an inhibitor of platelet aggregation, was found to protect animals from these adrenochrome effects [3].
• The depressant effects of adrenochrome on mitochondrial oxidative phosphorylation were additive to those seen with calcium [12].
• The left ventricular pressure (LVP) was significantly enhanced by adrenochrome (p < 0.05), but it fell thereafter to below its initial value in hearts treated with adrenochrome 10(-4) M [13].

Anatomical context of Adrenochrome

• Effects of adrenochrome on calcium accumulating and adenosine triphosphatase activities of the rat heart microsomes [14].
• Effect of adrenochrome on calcium accumulation by heart mitochondria [15].
• Adrenochrome-induced coronary artery constriction in the rat heart [16].
• It is proposed that cardiodepressant action of adrenochrome may partly be explained on the basis of its inhibitory effect on the calcium transporting ability of the sarcoplasmic reticulum [14].
• Adrenochrome concentrations of 10 or 25 mg/L altered the appearance of mitochondria after 30 minutes of perfusion [11].

Associations of Adrenochrome with other chemical compounds

• Our results indicated that adrenochrome was moderately stable in phosphate buffer but degraded rapidly (over 50% consumed in less than 2 min) by (cloned and expressed) CYP3A4 and CYP reductase in the presence of NADPH [8].
• O2-. production was demonstrated by cytochrome c reduction, adrenochrome formation and the effect of superoxide dismutase [17].
• Furthermore, both epinephrine and adrenochrome were found to be inhibitors of CYP3A4-mediated oxidation of testosterone [8].
• The adrenochrome reaction (oxidation of epinephrine to adrenochrome) has been widely employed as a standard assay for reactive oxygen species, produced under a variety of conditions, including those produced during cytochrome P450 (CYP)-mediated oxidation of substrates such as cyclosporine [8].
• It appears that captopril, in this respect, acted as a nonspecific antioxidant, probably by reducing an intermediate in the complex oxidation of epinephrine to adrenochrome [18].

Gene context of Adrenochrome

• A marked difference in the inhibitory effect of superoxide dismutase on oxygen consumption during adrenochrome reduction catalyzed by NADPH-cytochrome P450 reductase and DT-diaphorase was also observed [19].
• Catalase different significantly with respect to NADPH and NADH oxidation during reduction of adrenochrome catalyzed by NADPH-cytochrome P450 reductase and DT-diaphorase [19].
• Superoxide dismutase, catalase, and azide inhibited by 70-95% the oxidation of adrenaline to adrenochrome, either by cells or medium [20].
• HPLC of an extract of synovial fluid from a patient with rheumatoid arthritis, a fluid that contains polymorphonuclear leukocytes, showed a peak identical to that of the adrenochrome standard [20].
• Together, these results lead to the conclusion that the use of adrenochrome reaction for measurement of reactive oxygen species formed during CYP3A4-mediated metabolism of xenobiotics is inappropriate [8].

Analytical, diagnostic and therapeutic context of Adrenochrome

• Increasing the Ca2+ or K+ concentration or decreasing the Na+ concentration of the adrenochrome-containing perfusion medium partially maintained contractile force but increased the severity of ultrastructural damage [21].
• Adrenochrome-treatment (10(-6) M or 10(-4) M) was started after a reperfusion period of 20 min [13].
• The cAMP level in the heart was determined by radioimmunoassay 2 and 30 min after administration of IPRO, oxidized IPRO, or adrenochrome at a single dose of 10.0 mg X kg-1 [22].
• A histochemical adrenochrome oxidation method localized epinephrine exclusively in the corneal epithelium and anterior stromal lamellae after iontophoresis [23].
• The effect of adrenochrome semicarbazide on the conformation of erythrocyte ghost membranes has been studied by ANS fluorescence, lipid and sulfhydryl spin labels and circular dichroism [24].

References