Exposure to β-carbolines norharman and harman

Pfau, Wolfgang; Skog, Kerstin

doi:10.1016/j.jchromb.2003.10.044

Cited by 198 publications

(184 citation statements)

References 98 publications

(171 reference statements)

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“…Similarly, β-carboline alkaloids produce toxic damage with significant loss of cerebellar Purkinje cells (Du et al, 1997;Milner et al, 1995;O'Hearn and Molliver, 1997;Robertson, 1980;Sinton et al, 1989). While β-carboline alkaloids are produced endogenously in the human body (Gearhart et al, 2000;Wakabayashi et al, 1997), one study estimated that dietary sources were fifty times greater than endogenous sources (Pfau and Skog, 2004). β-carboline alkaloids are primarily found in muscle foods (beef, chicken, pork, fish) at ng/g concentrations and cooking leads to increased concentrations (Gross et al, 1993;Layton et al, 1995;Skog, 1993;Skog et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…Brain concentrations are several fold higher than those in the blood in both exposed (i.e., harmane-injected) laboratory animals and in control animals (Anderson et al, 2006;Zetler et al, 1972). Although harmane is produced endogenously, it is also present in the diet (especially in meats but also in other foods) and exogenous exposure is thought to be the main source of the body's harmane (Pfau and Skog, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor

Louis

2008

NeuroToxicology

127

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Essential tremor (ET) is a widespread late-life neurological disease. Genetic and environmental factors likely play an etiological role. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing neurotoxin. In 2002, we demonstrated elevated blood harmane concentrations in an initial sample of 100 ET cases compared to 100 controls. Between 2002 and 2007, we assembled a new and larger sample of ET cases and controls. We now attempt to replicate our previous findings. Cases and controls were frequency-matched on age, gender, and race. Blood harmane concentrations were quantified by high performance liquid chromatography. Subjects comprised 150 ET cases and 135 controls (mean age 65.3 ± 15.5 vs. 65.5 ± 14.2 years, p = 0.94). Mean log blood harmane concentration was ∼50% higher in cases than controls (0.50 ± 0.54 g -10 /ml vs. 0.35 ± 0.62 g -10 /ml, p = 0.038). In a logistic regression analysis, log blood harmane concentration was associated with ET (OR adjusted 1.56, 95% CI 1.01 -2.42, p = 0.04), and odds of ET was 1.90 (95% CI 1.07 -3.39, p = 0.029) in the highest vs. lowest log blood harmane tertile. Log blood harmane was highest in ET cases with familial ET (0.53 ± 0.57 g -10 /ml), intermediate in cases with sporadic ET (0.43 ± 0.45 g -10 /ml) and lowest in controls (0.35 ± 0.62 g -10 /ml) (test for trend, p = 0.026). Blood harmane appears to be elevated in ET. The higher concentrations in familial ET suggests that the mechanism may involve genetic factors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor

Louis

2008

NeuroToxicology

127

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“…Harman and norharman are additional biologically active components of cigarette smoke (Pfau & Skog, 2004), although there is very little research on their interaction with nicotine. These compounds are MAO inhibitors (Herraiz, 2004) and may contribute to the MAO inhibition observed in smokers at the concentrations present in cigarette smoke (Rommelspacher, Meier-Henco, Smolka, & Kloft, 2002).…”

Section: Could Other Constituents Of Tobacco Impact the Threshold Formentioning

confidence: 99%

Impact of Tobacco Regulation on Animal Research: New Perspectives and Opportunities

Donny

Taylor

LeSage

et al. 2012

Nicotine & Tobacco Research

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Introduction: The Family Smoking Prevention and Tobacco Control Act in the United States and the World Health Organization Framework Convention on Tobacco or Health ratified by over 170 countries render scientific investigations into the abuse liability, harm, and effects of tobacco more critical than ever. A key area to explore relates to the potential regulation of nicotine content in cigarettes. Determining the nicotine content per cigarette below which smokers reliably reduce their consumption of and dependence on cigarettes, an idea proposed almost 20 years ago (Benowitz & Henningfield, 1994), could be a powerful approach to reduce the abuse liability and consequent harm from cigarettes. However, this approach is laden with potentially complex issues. Many of these complications can be studied using animal models, but they require a particular perspective.

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“…Alcohol metabolism may lead to the formation of a beta-carboline compound called harman (33,34), and alcoholic beverages frequently contain harman (35), which has moderate affinity for MAO-A. To avoid temporary occupancy effects of harman (10), [ 11 C]-harmine PET scanning was timed at a point when harman levels were negligible (36), which was verified by plasma sampling.…”

Section: Protocol On Day Of Pet Imagingmentioning

confidence: 99%

Greater Monoamine Oxidase A Binding in Alcohol Dependence

Matthews

Kish

et al. 2014

Biological Psychiatry

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Background-Alcohol dependence (AD) is a multiorgan disease in which excessive oxidative stress and apoptosis are implicated. Monoamine oxidase A (MAO-A) is an important enzyme on the outer mitochondrial membrane that participates in the cellular response to oxidative stress and mitochondrial toxicity. It is unknown whether MAO-A levels are abnormal in AD. We hypothesized that MAO-A V T , an index of MAO-A level, is elevated in the prefrontal cortex (PFC) during AD, because markers of greater oxidative stress and apoptosis are reported in the brain in AD and a microarray analysis reported greater MAO-A messenger RNA in the PFC of rodents exposed to alcohol vapor.

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Exposure to β-carbolines norharman and harman

Cited by 198 publications

References 98 publications

Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor

Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor

Impact of Tobacco Regulation on Animal Research: New Perspectives and Opportunities

Greater Monoamine Oxidase A Binding in Alcohol Dependence

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