Intracerebral injection of low amounts of norharman induces moderate Parkinsonism-like behavioral symptoms in rat

Esmaeili, Mohammad; Movahedi, Mohadeseh; Faraji, Ayda; Haghdoost-Yazdi, Hashem

doi:10.1016/j.ntt.2012.07.001

Cited by 14 publications

(6 citation statements)

References 39 publications

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“…By this way, OCT inhibition may contribute to the possible neurotoxicity of HAAs, including PhIP, Trp-P-1 and Trp-P-2 (Cruz-Hernandez et al, 2018;Naoi et al, 1989). In particular, OCT inhibition by harmane and norharmane may be involved in the neurological diseases thought to be promoted by these two HAAs, such as essential tremor and the Parkinson disease (Esmaeili et al, 2012;Lavita et al, 2016). Whether HAAs may in vivo reach concentrations required for inhibiting activities of OCTs remains however a key-point to consider.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of organic cation transporter (OCT) activities by carcinogenic heterocyclic aromatic amines

Sayyed

Camillerapp

Vée

et al. 2019

Toxicology in Vitro

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Carcinogenic heterocyclic aromatic amines (HAAs) interact with some drug transporters, like the efflux pump BCRP and the organic anion transporters OAT1 and OAT3. The present study was designed to determine whether they can also target activities of the organic cation transporters (OCTs), using mainly OCT1-, OCT2- and OCT3-overexpressing HEK293 cells. Fifteen HAAs were demonstrated to differently alter OCT activities; with a cut-off of at least 50% reduction of transporter activity by 100 μM HAAs, 5/15 HAAs, including Trp-P-1 and Trp-P-2, inhibited activities of OCT1, OCT2 and OCT3, whereas 7/15 HAAs, including PhIP and MeIQx, blocked those of OCT2 and OCT3, 1/15 HAAs reduced those of OCT1 and OCT2 and 2/15 HAAs, including AαC, only that of OCT2. IC values of Trp-P-1 and Trp-P-2 towards OCT activities were found to be in the 2-6 μM range, likely not relevant for human exposure to HAAs through smoking or the diet. Trp-P-1 and Trp-P-2 additionally failed to trans-stimulate OCT1 and OCT2 activities and exhibited similar accumulation in OCT1/2-transduced HEK293 cells and control HEK293-MOCK cells. These data demonstrate that HAAs, notably Trp-P-1 and Trp-P-2, interact with OCT1/2, without however being transported, thus likely discarding a major role for OCT1/2 in HAA systemic toxicokinetics.

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Section: Discussionmentioning

confidence: 99%

Inhibition of organic cation transporter (OCT) activities by carcinogenic heterocyclic aromatic amines

Sayyed

Camillerapp

Vée

et al. 2019

Toxicology in Vitro

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“…A single intracerebral injection of norharmane in rats induces moderate Parkinsonism-like behavioral symptoms. 62 Systematically administered norharmane, 2mono-N-methylated norharmanium cation (2-MeNH + ), and 9-mono-N′-methylnorharman (9-MeNH)-induced bradykinesia in mice. 63 Harmane and harmaline exposure impaired memory formation and caused amnesia in rodents.…”

Section: Haa Brain Entrymentioning

confidence: 99%

Potential Role of Heterocyclic Aromatic Amines in Neurodegeneration

Syeda

Cannon

2022

Chem. Res. Toxicol.

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Heterocyclic aromatic amines (HAAs) are mainly formed in the pyrolysis process during high-temperature cooking of meat. Meat consumption is very typical of the western diet, and the amount of meat consumption in the eastern countries is growing rapidly; HAAs represents widespread exposure. HAAs are classified as possible human carcinogens; numerous epidemiological studies have demonstrated regular consumption of meat with HAAs as risk factor for cancers. Specific HAAs have received major attention. For example, 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine has been extensively studied as a genotoxicant and mutagen, with emergent literature on neurotoxicity. Harmane has been extensively studied for a role in essential tremors and potentially Parkinson's disease (PD). Harmane levels have been demonstrated to be elevated in blood and brain in essential tremor patients. Meat consumption has been implicated in the etiology of neurodegenerative diseases; however, the role of toxicants formed during meat preparation has not been studied. Epidemiological studies are currently examining the association between HAAs and risk of neurodegenerative diseases such as essential tremors and PD. Studies from our laboratory and others have provided strong evidence that HAA exposure produces PD and Alzheimer's disease-relevant neurotoxicity in cellular and animal models. In this review, we summarize and critically evaluate previous studies on HAA-induced neurotoxicity and the molecular basis of potential neurotoxic effects of HAAs. The available studies provide strong support for the premise that HAAs may impact neurological function and that addressing gaps in understanding of adverse neurological outcomes is critical to determine whether these compounds are modifiable risk factors.

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“…In recent years, interest in the investigation of norharman has increased due to its occurrence in food and in environmental samples, and because it is also an endogenous compound in the human body. 8,[16][17][18][19] Norharman is considered an endogenous neurotoxin that induces idiopathic Parkinson's disease 20,21 and there are reports linking this compound to various biochemical, pharmacological and toxic effects, 22 suggesting that this compound may be neurotoxic. These reports show the importance in the development of methods for identification and quantification of norharman for the study P. edulis rinds as a source of this compound.…”

Section: Introductionmentioning

confidence: 99%

SBSE(EG-Silicone)-UFLC-MS/MS and HPLC-Flu Analysis of Norharman in Passiflora edulis Rinds

Freire

Colombo

Yariwake

2019

J. Braz. Chem. Soc.

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Previous studies on Passiflora edulis (sour passion fruit) rinds reported some biological activities and there is a growing interest on rinds flour as a possible functional food, but its alkaloid composition was not detailed investigated. This work reports on for the first time in the literature the identification of norharman in P. edulis rinds, by using stir bar sorptive extraction combined with ultra-fast liquid chromatography coupled to tandem mass spectrometry [SBSE(EG-Silicone)-UFLC-MS/MS)]. This β-carboline alkaloid is suspected to be neurotoxic. Therefore, another purpose of this study was to develop methods of targeted quantification of norharman in P. edulis rinds extracts using polydimethylsiloxane as stationary phase (SBSE(PDMS)) and a copolymer of polydimethylsiloxane and polyethylene glycol as stationary phase (SBSE(EG-Silicone)) combined with high performance liquid chromatography with fluorescence detection (HPLC-Flu) and ultra-fast liquid chromatography coupled with tandem mass spectrometry (UFLC-MS/MS). Norharman extraction by SBSE(PDMS) and SBSE(EG-Silicone) was optimized and compared, and the analytical performance of SBSE(EG-Silicone) method was superior to that of SBSE(PDMS). The analysis of a sample of dried P. edulis rind indicated (332.16 ± 8.43) pg g-1 of norharman.

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Intracerebral injection of low amounts of norharman induces moderate Parkinsonism-like behavioral symptoms in rat

Cited by 14 publications

References 39 publications

Inhibition of organic cation transporter (OCT) activities by carcinogenic heterocyclic aromatic amines

Inhibition of organic cation transporter (OCT) activities by carcinogenic heterocyclic aromatic amines

Potential Role of Heterocyclic Aromatic Amines in Neurodegeneration

SBSE(EG-Silicone)-UFLC-MS/MS and HPLC-Flu Analysis of Norharman in Passiflora edulis Rinds

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