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Tomas Herraiz - One of the best experts on this subject based on the ideXlab platform.

  • Oxidative metabolism of the bioactive and naturally occurring Beta-Carboline alkaloids, norharman and harman, by human cytochrome P450 enzymes.
    Chemical research in toxicology, 2008
    Co-Authors: Tomas Herraiz, Hugo Guillén, Vicente J. Arán
    Abstract:

    Norharman and harman are naturally occurring Beta-Carboline alkaloids exhibiting a wide range of biological, psychopharmacological, and toxicological actions. They occur in foods and tobacco smoke and also appear endogenously in humans. In this research, metabolic and kinetic studies with cytochrome P450 enzymes and human liver microsomes showed that Beta-Carbolines were efficiently oxidized to several ring-hydroxylated and N-oxidation products that were subsequently identified and quantified. 6-Hydroxy- Beta-Carboline (6-hydroxynorharman and 6-hydroxyharman) was a major metabolite efficiently produced (high kcat and low Km) by P450 1A2 and 1A1 and to a minor extent by P450 2D6, 2C19 and 2E1. 3-Hydroxy-Beta-Carboline (3-hydroxynorharman and 3-hydroxyharman), another major metabolite, was specifically produced by P450 1A2 and 1A1, whereas Beta-Carboline-N(2)-oxide (harman-2-oxide and norharman-2-oxide) was produced by P450 2E1. The same pattern of metabolism was confirmed for human liver microsomes. Oxidative metabolism for harman was slightly higher than norharman, but norharman showed lower Km values. The oxidation of Beta-Carbolines is a detoxication route performed mainly by P450 1A2 and 1A1, with the participation of P450 2D6, 2C19, and 2E1, as additional contributors. Then, individual variations in the levels and activity of these P450s may influence biotransformation of Beta-Carboline alkaloids and their ultimate biological effects. Beta-Carbolines were previously reported as comutagens and/or inhibitors of mutagens activated by P450 1A enzymes such as heterocyclic amines and polycyclic hydrocarbons. Results in this work show that Beta-Carbolines are good ligands and substrates for P450 1A2/1A1, contributing to the explanation of some of their toxicological effects.

  • identification and occurrence of beta carboline alkaloids in raisins and inhibition of monoamine oxidase mao
    Journal of Agricultural and Food Chemistry, 2007
    Co-Authors: Tomas Herraiz
    Abstract:

    Monoamine oxidase (MAO) is a mitochondrial enzyme involved in the oxidative catabolism of neurotransmitters and xenobiotic amines, including vasopressor and neurotoxic amines, and a current target for antidepressant and neuroprotective drugs. Raisin extracts and homogenates exhibited reversible in vitro inhibition of MAO isozymes, particularly MAO-A, suggesting the presence of MAO-inhibiting substances. Chromatographic and spectrometric studies showed the occurrence of aromatic Beta-Carboline alkaloids in raisins, and norharman and harman were identified as the key contributors to MAO inhibition. On average, harman ranged from 6 to 644 ng/g and norharman from 2 to 120 ng/g. Several technological variables appeared to determine the presence of these compounds in raisins. Dark-brown raisins (i.e., sun-dried) contained much higher levels than golden raisins. Tetrahydro-Beta-Carboline-3-carboxylic acid compounds that are direct precursors of aromatic Beta-Carbolines were also identified in raisins and appeared in a higher amount, reaching up to 50 microg/g. Beta-Carbolines were isolated from raisins and acted as good competitive inhibitors of MAO-A (harman) and MAO-B (norharman) isozymes. These results suggest that Beta-Carboline alkaloids and perhaps raisins containing a high level of Beta-Carbolines might exhibit potential activity as MAO inhibitors. The results also show that some raisins can be a source of dietary exposure to bioactive Beta-Carbolines.

  • Analysis of monoamine oxidase enzymatic activity by reversed-phase high performance liquid chromatography and inhibition by Beta-Carboline alkaloids occurring in foods and plants.
    Journal of chromatography. A, 2005
    Co-Authors: Tomas Herraiz, Carolina Chaparro
    Abstract:

    Monoamine oxidase (MAO) is a flavin adenine dinucleotide (FAD)-containing enzyme located at the outer membranes of mitochondria that catalyzes the oxidative deamination of biogenic and xenobiotic amines. We have used a chromatographic method to measure MAO-enzymatic activity by using kynuramine as a non-selective substrate with its MAO-oxidation product subsequently analyzed by RP-HPLC-DAD and HPLC-mass spectrometry (MS). This method was applied to study the kinetic parameters, inhibition and reaction products of MAO recombinant enzymes in presence of tetrahydro-Beta-Carboline and Beta-Carboline alkaloids occurring in foods, plants and mammals. Analysis by HPLC showed that tetrahydro-Beta-Carbolines or Beta-Carbolines were not modified by MAO. Several Beta-Carbolines such as tryptoline (1,2,3,4-tetrahydro-Beta-Carboline) and 1-methyltryptoline (1-methyl-1,2,3,4-tetrahydro-Beta-Carboline) were inhibitors of MAO-A; instead their corresponding 6-hydroxy-derivatives (6-hydroxytryptoline and 6-hydroxy-1-methyltryptoline) lacked this activity. Tetrahydro-Beta-Carboline-3-carboxylic acids were unable to inhibit MAO enzymes. In contrast, their oxidation products, i.e. the fully aromatic Beta-Carbolines (norharman and harman), acted as good inhibitors of MAO. Two tetrahydro-Beta-Carbolines (i.e. tryptoline and 1-methyltryptoline) occurring in foods were isolated by solid-phase extraction (SPE) and RP-HPLC from selected samples of sausages and the corresponding extracts exhibited good inhibition properties over MAO-A. These results suggest that Beta-Carbolines from foods, plants, and mammals may exert inhibitory actions on MAO enzymes.

  • Endogenous and dietary indoles: a class of antioxidants and radical scavengers in the ABTS assay.
    Free radical research, 2004
    Co-Authors: Tomas Herraiz, Juan Galisteo
    Abstract:

    Indoles are very common in the body and diet and participate in many biochemical processes. A total of twenty-nine indoles and analogs were examined for their properties as antioxidants and radical scavengers against 2,2'-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) ABTS*+ radical cation. With only a few exceptions, indoles reacted nonspecifically and quenched this radical at physiological pH affording ABTS. Indoleamines like tryptamine, serotonin and methoxytryptamine, neurohormones (melatonin), phytohormones (indoleacetic acid and indolepropionic acid), indoleamino acids like L-tryptophan and derivatives (N-acetyltryptophan, L-abrine, tryptophan ethyl ester), indolealcohols (tryptophol and indole-3-carbinol), short peptides containing tryptophan, and tetrahydro-Beta-Carboline (pyridoindole) alkaloids like the pineal gland compound pinoline, acted as radical scavengers and antioxidants in an ABTS assay-measuring total antioxidant activity. Their trolox equivalent antioxidant capacity (TEAC) values ranged from 0.66 to 3.9 mM, usually higher than that for Trolox and ascorbic acid (1 mM). The highest antioxidant values were determined for melatonin, 5-hydroxytryptophan, trp-trp and 5-methoxytryptamine. Active indole compounds were consumed during the reaction with ABTS*+ and some tetrahydropyrido indoles (e.g. harmaline and 1-methyl-1,2,3,4-tetrahydro-Beta-Carboline-3-carboxylic acid ethyl ester) afforded the corresponding fully aromatic Beta-Carbolines (pyridoindoles), that did not scavenge ABTS*+. Radical scavenger activity of indoles against ABTS*+ was higher at physiological pH than at low pH. These results point out to structural compounds with an indole moiety as a class of radical scavengers and antioxidants. This activity could be of biological significance given the physiological concentrations and body distribution of some indoles.

  • Tetrahydro-Beta-Carboline-3-carboxylic acid compounds in fish and meat: possible precursors of co-mutagenic Beta-Carbolines norharman and harman in cooked foods.
    Food additives and contaminants, 2000
    Co-Authors: Tomas Herraiz
    Abstract:

    The presence of tetrahydro-Beta-Carbolines and Beta-Carbolines was studied in raw, cooked and smoked fish and meat. 1,2,3,4-Tetrahydro-Beta-Carboline-3-carboxylic acid (THCA) usually was the major Beta-Carboline found, whereas 1-methyl-1,2,3,4-tetrahydro-Beta-Carboline-3-carboxylic acid (MTCA) appeared in smoked and 'well done' cooked samples. THCA was detected in raw fish (nd-2.52 micrograms/g), cooked fish (nd-6.43 micrograms/g), cooked meats (nd-0.036 microgram/g), smoked fish (0.19-0.67 microgram/g) and smoked meats (0.02-1.1 micrograms/g). Smoked and cooked samples contained higher amounts of THCA and MTCA than raw products. Deep cooking of fish and meat increased both THCA and MTCA, and this was accompanied by the formation of more Beta-Carbolines, norharman and harman. The tetrahydro-Beta-Carbolines THCA and MTCA were chemical precursors of the co-mutagens norharman and harman during cooking. These and previous results confirm that foods are an important source of Beta-Carbolines in humans.

Yoon Young Jang - One of the best experts on this subject based on the ideXlab platform.

  • Protective effect of harmaline and harmalol against dopamine‐ and 6‐hydroxydopamine‐induced oxidative damage of brain mitochondria and synaptosomes, and viability loss of PC12 cells
    European Journal of Neuroscience, 2001
    Co-Authors: Yoon Young Jang
    Abstract:

    : The present study elucidated the protective effect of Beta-Carbolines (harmaline, harmalol and harmine) against oxidative damage of brain mitochondria, synaptosomes and PC12 cells induced by either dopamine or 6-hydroxydopamine. Harmaline, harmalol and antioxidant enzymes (superoxide dismutase/SOD and catalase) decreased the alteration of mitochondrial swelling and membrane potential induced by 200 microM dopamine or 100 microM 6-hydroxydopamine. Deprenyl attenuated the dopamine-induced mitochondrial dysfunction but did not reduce the effect of 6-hydroxydopamine. While Beta-Carbolines inhibited the electron flow in mitochondria, they did not enhance the depressant effect of catecholamines. Beta-Carbolines and antioxidant enzymes reversed the depression of synaptosomal Ca2+ uptake induced by 10 microM catecholamines. The compounds inhibited the catecholamine-induced thioredoxin reductase inhibition, thiol oxidation and carbonyl formation in mitochondria and synaptosomes. Beta-Carbolines decreased the reactive species-induced deoxyribose degradation. Harmaline and harmalol reduced the catecholamine-induced loss of the transmembrane potential and of cell viability in PC12 cells. Beta-Carbolines alone did not show a significant cytotoxic effect on PC12 cells. The results suggest that Beta-Carbolines may attenuate the dopamine- or 6-hydroxydopamine-induced alteration of brain mitochondrial and synaptosomal functions, and viability loss in PC12 cells, by a scavenging action on reactive oxygen species and inhibition of thiol oxidation.

  • protective effect of harmaline and harmalol against dopamine and 6 hydroxydopamine induced oxidative damage of brain mitochondria and synaptosomes and viability loss of pc12 cells
    European Journal of Neuroscience, 2001
    Co-Authors: Yoon Young Jang
    Abstract:

    : The present study elucidated the protective effect of Beta-Carbolines (harmaline, harmalol and harmine) against oxidative damage of brain mitochondria, synaptosomes and PC12 cells induced by either dopamine or 6-hydroxydopamine. Harmaline, harmalol and antioxidant enzymes (superoxide dismutase/SOD and catalase) decreased the alteration of mitochondrial swelling and membrane potential induced by 200 microM dopamine or 100 microM 6-hydroxydopamine. Deprenyl attenuated the dopamine-induced mitochondrial dysfunction but did not reduce the effect of 6-hydroxydopamine. While Beta-Carbolines inhibited the electron flow in mitochondria, they did not enhance the depressant effect of catecholamines. Beta-Carbolines and antioxidant enzymes reversed the depression of synaptosomal Ca2+ uptake induced by 10 microM catecholamines. The compounds inhibited the catecholamine-induced thioredoxin reductase inhibition, thiol oxidation and carbonyl formation in mitochondria and synaptosomes. Beta-Carbolines decreased the reactive species-induced deoxyribose degradation. Harmaline and harmalol reduced the catecholamine-induced loss of the transmembrane potential and of cell viability in PC12 cells. Beta-Carbolines alone did not show a significant cytotoxic effect on PC12 cells. The results suggest that Beta-Carbolines may attenuate the dopamine- or 6-hydroxydopamine-induced alteration of brain mitochondrial and synaptosomal functions, and viability loss in PC12 cells, by a scavenging action on reactive oxygen species and inhibition of thiol oxidation.

Karl-heinz Sontag - One of the best experts on this subject based on the ideXlab platform.

  • Biochemical lesions of the nigrostriatal system by TaClo (1-trichloromethyl-1,2,3,4-tetrahydro-Beta-Carboline) and derivatives.
    Journal of neural transmission. Supplementum, 1995
    Co-Authors: C. Grote, Hans-willi Clement, Wolfgang Wesemann, Gerhard Bringmann, Doris Feineis, P. Riederer, Karl-heinz Sontag
    Abstract:

    In vivo voltammetry with carbon fibre electrodes was used to study the effects of highly halogenated tetrahydro-Beta-Carbolines on the striatal dopamine (DA) metabolism of the rat. As representatives of chloral-derived heterocycles, "TaClo" (1-trichloro-1,2,3,4-tetrahydro-Beta-Carboline) and its N-methylated derivative. "N-methyl-TaClo", were investigated. After intranigral injection of 10 micrograms TaClo, the DA activity in the ipsilateral striatum was reduced compared with the intact side. Application of N-methyl-TaClo (10 micrograms) resulted in a nearly total reduction of the DOPAC signal. Furthermore, also "TaBro" (1-tribromomethyl-1,2,3,4-tetrahydro-Beta-Carboline), the bromal-derived analogue of TaClo, was tested. The impairment of the DA metabolism in rats achieved with 10 micrograms TaBro was found to be between that observed after application of TaClo and N-methyl-TaClo, respectively. The results demonstrate the toxic potential of chloral- and bromal-derived Beta-Carbolines towards dopaminergic neurons.

T Herraiz - One of the best experts on this subject based on the ideXlab platform.

Carolina Chaparro - One of the best experts on this subject based on the ideXlab platform.

  • Analysis of monoamine oxidase enzymatic activity by reversed-phase high performance liquid chromatography and inhibition by Beta-Carboline alkaloids occurring in foods and plants.
    Journal of chromatography. A, 2005
    Co-Authors: Tomas Herraiz, Carolina Chaparro
    Abstract:

    Monoamine oxidase (MAO) is a flavin adenine dinucleotide (FAD)-containing enzyme located at the outer membranes of mitochondria that catalyzes the oxidative deamination of biogenic and xenobiotic amines. We have used a chromatographic method to measure MAO-enzymatic activity by using kynuramine as a non-selective substrate with its MAO-oxidation product subsequently analyzed by RP-HPLC-DAD and HPLC-mass spectrometry (MS). This method was applied to study the kinetic parameters, inhibition and reaction products of MAO recombinant enzymes in presence of tetrahydro-Beta-Carboline and Beta-Carboline alkaloids occurring in foods, plants and mammals. Analysis by HPLC showed that tetrahydro-Beta-Carbolines or Beta-Carbolines were not modified by MAO. Several Beta-Carbolines such as tryptoline (1,2,3,4-tetrahydro-Beta-Carboline) and 1-methyltryptoline (1-methyl-1,2,3,4-tetrahydro-Beta-Carboline) were inhibitors of MAO-A; instead their corresponding 6-hydroxy-derivatives (6-hydroxytryptoline and 6-hydroxy-1-methyltryptoline) lacked this activity. Tetrahydro-Beta-Carboline-3-carboxylic acids were unable to inhibit MAO enzymes. In contrast, their oxidation products, i.e. the fully aromatic Beta-Carbolines (norharman and harman), acted as good inhibitors of MAO. Two tetrahydro-Beta-Carbolines (i.e. tryptoline and 1-methyltryptoline) occurring in foods were isolated by solid-phase extraction (SPE) and RP-HPLC from selected samples of sausages and the corresponding extracts exhibited good inhibition properties over MAO-A. These results suggest that Beta-Carbolines from foods, plants, and mammals may exert inhibitory actions on MAO enzymes.