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Photosensitized transformation of adrenochrome.

The methylene blue-sensitized photooxidation of adrenochrome was studied by steady-state kinetics. The buffered, aqueous system was irradiated with light longer than 600 nm, wavelengths at which only the sensitizer absorbs. During irradiation, disappearance of adrenochrome and the formation of adrenochrome-melanin was observed. Calculated rate constants were determined on the basis of spectroscopic measurements. It was found that the observed transformation reaction steps are pH dependent. The participation of two types of photosensitized mechanism has been evidenced. Type II, singlet oxygen mechanism, predominates at pH below 9, whereas above pH 9, Type I applies. We observed the so-called "isotope effect" and a decrease of photooxidation rate in the presence of azide ion, a well-known singlet oxygen quencher, indicating the participation of singlet oxygen.

Adrenochrome↗

[NADPH2 and organic hydroperoxide-dependent oxidation of adrenaline to adrenochromes in liver and brain microsomes].

It was shown that oxidation of adrenaline to adrenochrome in microsomal membranes of the brain and liver in the presence of NADP . H2 or NAD . H2 is mainly accounted for by the formation of a superoxide anion radical. The formation of adrenochrome from adrenalin was found to depend on organic hydroperoxides (natural and synthetic). The organic hydroperoxide-dependent oxidation of adrenochrome involves singlet oxygen. In microsomal fractions of the liver the organic peroxide-dependent oxidation of adrenalin was catalyzed by cytochrome P-450.

Adrenochrome↗

[Effect of adrenochrome on the neuronal membrane of the mollusk Helix pomatia].

The influence of adrenochrome on the electrical characteristics of Helix pomatia neurons was examined. Application of adrenochrome transformed neuronal regular rhythmic activity into bursting one. Anomalous rectification was seen. The voltage clamp technique showed that the action of adrenochrome lowered both inward and outward currents.

Action Potentials↗

Adrenochrome reaction implicates oxygen radicals in metabolism of cyclosporine A and FK-506 in rat and human liver microsomes.

The role of oxygen radicals in the metabolism of cyclosporine A (CyA), FR900506 (FK-506) and carbon tetrachloride (CCl4) catalyzed by the cytochrome P450 system was investigated in vitro in rat and human microsomal preparations. Varying concentrations of CyA, FK-506 and CCl4 (100 microM-1.0 mM) were added to microsomal preparations, and lipid peroxidation was measured by malondialdehyde (MDA) formation as detected by the thiobarbituric acid assay. The effects of oxygen radical scavengers [superoxide dismutase (SOD) and catalase (CAT)] and an antioxidant [glutathione (GLUT)] were tested on various incubations of CyA, FK-506 and CCl4 to assess the role of oxygen radicals in lipid peroxidation. CyA-dependent MDA formation was moderately inhibited by SOD in the rat model and increased by SOD in the human model. In both models, CAT slightly inhibited CyA-dependent MDA formation and GLUT significantly inhibited MDA formation. FK-506-dependent MDA formation, studied only in the rat model, paralleled CyA-induced MDA formation but showed greater inhibition with CAT and less inhibition with SOD or GLUT. In both models, CCl4-dependent MDA formation was significantly inhibited by GLUT and showed no sensitivity to SOD or CAT. In addition, the adrenochrome reaction, which measures the oxidation of epinephrine to adrenochrome, was used to measure the increased oxygen radical-flux resulting from the metabolism of CyA, FK-506 and CCl4. CyA with epinephrine showed the highest oxidative activity, followed by FK-506 and then CCl4, which showed the least formation of adrenochrome. These results indicated a role for oxygen radicals in CyA and FK-506 metabolism.

Adrenochrome↗

Radical anions from one-electron-reduced adrenochrome. Detection and identification by electron spin resonance spectroscopy.

Free radicals from the one-electron reduction of adrenochrome have been studied in aqueous solutions. These radicals have been detected and identified by electron spin resonance spectroscopy, using spin stabilization methods (complexation with diamagnetic metal ions) to enhance radical concentrations. It is shown that the radicals have a characteristic ESR spectrum enabling their identification in complex systems. The spin density distribution in the radicals has been studied as a function of complexing metal ions and solvent composition. In the presence of oxidants (e.g., oxygen) the spectrum of the radical is replaced by that derived from the one-electron exidation of adrenochrome.

Adrenochrome↗

Redox cycling of adrenaline and adrenochrome catalysed by mitochondrial Complex I.

Complex I in bovine heart submitochondrial particles catalyses the NADH-supported generation of superoxide anion; adrenaline is oxidised by superoxide to adrenochrome that, on its hand, is reduced by Complex I, thus establishing a redox cycle that amplifies the superoxide production. The routes in Complex I for superoxide formation and for adrenochrome reduction appear to be different, since they have a different sensitivity to Complex I inhibitors. The results are discussed in terms of current assays for superoxide detection and of pathologies linked to catecholamine oxidation.

Adrenochrome↗

Schizophrenia and cancer: the adrenochrome balanced morphism.

Cancer might be expected to be more common amongst schizophrenics than the general population. They frequently live in selenium deficient regions, have seriously compromised antioxidant defense systems and chain-smoke. The available literature on the cancer-schizoprenia relationship in patients from England, Wales, Ireland, Denmark, USA and Japan, however, strongly suggests that the reverse is true. One of the authors (Hoffer) has treated 4000 schizophrenics since 1952. Only four of these patients has developed cancer. Since low cancer incidence has been recorded amongst patients treated by both conventional physicians using pharmaceuticals and by orthomolecular doctors who emphasize vitamins and minerals, it follows that this depressed cancer incidence must be related to the biochemistry of the disorder itself. Taken as a whole, therefore, the evidence seems to suggest that schizophrenics, their siblings and parents are less susceptible to cancer than the general population. These relationships seem compatible with one or more genetic risk factors for schizophrenia that offer(s) a selective advantage against cancer. There is experimental evidence that appears to support this possibility. Matrix Pharmaceuticals Inc. has received a US patent covering the composition of IntraDose Injectable Gel. This gel contains cisplatin and epinephrine (adrenaline) and is designed to be injected directly into tumour masses. Cisplatin is a very powerful oxidant which will almost certainly rapidly convert the adrenaline to adrenochrome. While the manufacturers of IntraDose consider cisplatin to be the active cytotoxic agent in IntraDose, it seems more likely that adrenochrome and its derivatives may, in fact, be more effective. IntraDose gel has undergone or is undergoing a series of Phase III open-label clinical studies, being injected into patients' tumours that have been identified as the most troublesome by their physicians. The results have been impressive for breast cancer, malignant melanoma, esophageal cancer and cancer of the head, neck and liver. The evidence suggests that there are balanced morphisms in schizophrenia that result in above normal exposure to catecholamine derivatives. Since such catecholamines are both hallucinogenic and anticarcinogenic abnormally high exposure to them simultaneously increases susceptibility to schizophrenia and reduces the probability of developing cancer. These observations have significant implications for the treatment of both illnesses.

Adrenochrome↗

[Effect of adrenochrome on electrical characteristics of Helix pomatia mollusk neurons].

Helix pomatia neurons were used as test-objects in the study of adrenochrome effect on nerve tissue by the microelectrode technique and voltage clamp. The action of adrenochrome consists in slow de- and hyperpolarization of the neuronal membrane and in the appearance of periodic short-term shifts in the membrane potential. The lowering of the action potential amplitude is as consequence of the decreased maximal conduction of inward current ionic channels.

Action Potentials↗

The role of adrenochrome in stimulating the oxidation of catecholamines.

Adrenochrome, a stable oxidation product formed after oxidation of adrenaline, strongly stimulates oxygen uptake occurring during the autoxidation of adrenaline, other catecholamines and ascorbate. Oxygen consumed is converted to hydrogen peroxide suggesting the occurrence of a redox cycling process. The reduction of adrenochrome operated by adrenaline is accelerated by the exclusion of oxygen indicating that the oxidation of adrenaline occurs directly and superoxide anion does not necessarily mediate it. Oxygen consumption, observed in the catecholamine/adrenochrome and ascorbate/adrenochrome systems, is due to the autoxidation of leucoadrenochrome that, at variance with adrenaline, easily autoxidizes also at physiological pH. Therefore, in these systems, leucoadrenochrome appears to be the major determinant of the production of superoxide anion.

Journal Article↗

In vitro haemolysis from adrenochrome in the blood of schizophrenic patients, revised.

The recently reported abnormal in vitro haemolysis from catecholamine metabolites in schizophrenia was tested. We did not find the postulated increase in haemolysis, though the exchange of plasma for Ringer solution renders some patients' erythrocytes more susceptible to the effects of adrenochrome. The possibility of a subgroup of schizophrenia with a defect in membrane stability is discussed.

Adolescent↗

Formation of adrenochrome by bovine cardiac sarcolemma.

A sarcolemma preparation from bovine heart was able to promote adrenaline oxidation especially when NADH and NADPH were added. The superoxide anion O(2) was demonstrated to be involved in the activation of adrenochrome production.

Adrenochrome↗

Partial characterization of the 1-anilino-8-naphthalene sulfonate-adrenochrome semicarbazide interaction site in erythrocyte ghost membrane fragments.

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. No large conformational alterations in the membrane were detected by these techniques. Noncompetitive quenching of ANS fluorescence by ADCS suggests ADCS to interact with the membrane at sites close to the ANS binding domain.

Adrenochrome↗

Effects of combination of immunomodulators and an adrenochrome derivative on survival of irradiated mice.

PURPOSE: The combined effects of immunomodulators (lithium or OK432) and an adrenochrome derivative (AMM), an agent found to activate granulocyte-macrophage colony stimulating activity, on the survival of irradiated ddY mice is described. METHODS AND MATERIALS: ddY mice at 4-5 weeks old were whole body irradiated with X rays at 8.5 Gy. Sole injection and combined injection of AMM and/or one of the immunomodulators were performed before or after irradiation. Then, survival was monitored daily for 30 days after irradiation. RESULTS: Lithium at 60 mg/kg had no radioprotective effect; rather it accelerated radiation induced death. Sole treatment with AMM (100 mg/kg) had no effect on survival of irradiated mice. However, combination of both drugs caused a slight radioprotection. OK432 (25 KE/kg), which activates a variety of cellular effector cells had radioprotective effect. When combined with AMM, however, it totally lost radioprotective effect. CONCLUSION: Lithium chloride cannot be used as a radioprotector because of its adverse effect. Combination with AMM showed slight radioprotection, but the extent thereof may not be clinically useful. OK432 was proved to be a potent radioprotector. However, combination with AMM should be avoided, since the radioprotection was totally eliminated.

Adjuvants, Immunologic↗

Persistent corneal erosion secondary to tarsal adrenochrome deposit.

A 64-year-old man with open-angle glaucoma had used topically applied epinephrine for 13 years. He developed a foreign-body sensation and persistent superotemporal corneal erosion as a result fo an adrenochrome deposit on the upper tarsus. Removal of the deposit ended the corneal erosion and returned visual acuity to normal.

Adrenochrome↗

Noradrenaline, propranolol and adrenochrome interactions with the dynamic of haemolymph lipids in worker honeybees.

Injection of worker honeybees with noradrenaline, in vivo, depresses the haemolymph levels of phospholipid, steroid and triacylglycerols. The major fatty acids fraction shows large amplitude variations which seem to be dependent on several distinct factors. Adrenochrome exhibits a tendency to induce global hypoglycemic effects without evident correlation with the other hormones, whereas propranolol counteracts the effects of noradrenaline, particularly for phospholipids, steroids and diacylglycerols. The results suggest that the major lipoproteic complex is partly under the control of low specificity adrenoceptors.

Adrenochrome↗

Adrenochrome staining of soft contact lenses.

A clinical case of adrenochrome staining of a soft contact lens is described. A laboratory model for such staining is then described in which a soft lens is boiled in a basic, saturated solution of L-DOPA. Repetition of this process in fresh solutions of L-DOPA can achieve any level of black staining desired. The lens can then be made transparent by immersing it in a 3% solution of hydrogen.

Adrenochrome↗