scholarly journals The Influence of Monoamine Oxidase Variants on the Risk of Betel Quid-Associated Oral and Pharyngeal Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Ping-Ho Chen ◽  
Bin Huang ◽  
Tien-Yu Shieh ◽  
Yan-Hsiung Wang ◽  
Yuk-Kwan Chen ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Betel Quid ◽  
International Agency ◽  
Pharyngeal Cancer ◽  
Oral Potentially Malignant Disorders ◽  
Group I ◽  
Oral And Pharyngeal Cancer ◽  
Mao A ◽  
Potentially Malignant

Betel quid (BQ) and areca nut (AN) (major BQ ingredient) are group I human carcinogens illustrated by International Agency for Research on Cancer and are closely associated with an elevated risk of oral potentially malignant disorders (OPMDs) and cancers of the oral cavity and pharynx. The primary alkaloid of AN, arecoline, can be metabolizedviathe monoamine oxidase (MAO) gene by inducing reactive oxygen species (ROS). The aim of this study was to investigate whether the variants of the susceptible candidate MAO genes are associated with OPMDs and oral and pharyngeal cancer. A significant trend of MAO-A mRNA expression was found inin vitrostudies. Using paired human tissues, we confirmed the significantly decreased expression of MAO-A and MAO-B in cancerous tissues when compared with adjacent noncancerous tissues. Moreover, we determined that MAO-A single nucleotide polymorphism variants are significantly linked with oral and pharyngeal cancer patients in comparison to OPMDs patients [rs5953210 risk G-allele, odds ratio = 1.76; 95% confidence interval = 1.02-3.01]. In conclusion, we suggested that susceptible MAO family variants associated with oral and pharyngeal cancer may be implicated in the modulation of MAO gene activity associated with ROS.

scholarly journals Adverse Health Effects of Betel Quid and the Risk of Oral and Pharyngeal Cancers

2017 ◽  
Vol 2017 ◽  
pp. 1-25 ◽  
Author(s):  
Ping-Ho Chen ◽  
Qaisar Mahmood ◽  
Gian Luigi Mariottini ◽  
Tai-An Chiang ◽  
Ka-Wo Lee
Keyword(s):  
Health Effects ◽  
Molecular Mechanisms ◽  
Betel Quid ◽  
Pharyngeal Cancer ◽  
Oral Potentially Malignant Disorders ◽  
Adverse Health Effects ◽  
Adverse Health ◽  
Close Relationship ◽  
Potentially Malignant ◽  
Comparison Data

Global reports estimate 600 million betel quid (BQ) chewers. BQ chewing has been demonstrated not only to be a risk factor for cancers of the oral cavity and pharynx and oral potentially malignant disorders (OPMD) but also to cause other cancers and adverse health effects. Herein, we summarized the international comparison data to aid in the understanding of the close relationship between the prevalence of BQ chewing, the occurrence of oral and pharyngeal cancers, and adverse health effects. Potential biomarkers of BQ carcinogens, such as areca nut, alkaloids, and 3-methylnitrosaminopropionitrile (MNPN), are closely associated with human health toxicology. Molecular mechanisms or pathways involving autophagy, hypoxia, COX-2, NF-κB activity, and stemness are known to be induced by BQ ingredients and are very closely related to the carcinogenesis of cancers of oral and pharynx. BQ abuse-related monoamine oxidase (MAO) gene was associated with the occurrence and progress of oral and pharyngeal cancers. In summary, our review article provides important insights into the potential roles of environmental BQ (specific alkaloid biomarkers and nitrosamine products MNPN) and genetic factors (MAO) and offers a basis for studies aiming to reduce or eliminate BQ-related OPMD and oral/pharyngeal cancer incidences in the future.

scholarly journals Cytochrome P450 Metabolism of Betel Quid-Derived Compounds: Implications for the Development of Prevention Strategies for Oral and Pharyngeal Cancers

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Che-Yi Lin ◽  
Tien-Szu Pan ◽  
Chun-Chan Ting ◽  
Shih-Shin Liang ◽  
Shu-Hung Huang ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Oral Cavity ◽  
Current Knowledge ◽  
Metabolic Activation ◽  
Screening Tests ◽  
Betel Quid ◽  
Diagnostic Tools ◽  
International Agency ◽  
Oral Potentially Malignant Disorders ◽  
Group I

Betel quid (BQ) products, with or without tobacco, have been classified by the International Agency for Research on Cancer (IARC) as group I human carcinogens that are associated with an elevated risk of oral potentially malignant disorders (OPMDs) and cancers of the oral cavity and pharynx. There are estimated 600 million BQ users worldwide. In Taiwan alone there are 2 million habitual users (approximately 10% of the population). Oral and pharyngeal cancers result from interactions between genes and environmental factors (BQ exposure). Cytochrome p450 (CYP) families are implicated in the metabolic activation of BQ- and areca nut-specific nitrosamines. In this review, we summarize the current knowledge base regardingCYPgenetic variants and related oral disorders. In clinical applications, we focus on cancers of the oral cavity and pharynx and OPMDs associated withCYPgene polymorphisms, includingCYP1A1,CYP2A6,CYP2E1, andCYP26B1. Our discussion ofCYPpolymorphisms provides insight into the importance of screening tests in OPMDs patients for the prevention of oral and pharyngeal cancers. Future studies will establish a strong foundation for the development of chemoprevention strategies, polymorphism-based clinical diagnostic tools (e.g., specific single-nucleotide polymorphism (SNP) “barcodes”), and effective treatments for BQ-related oral disorders.

scholarly journals In Vitro,In Vivo, and Clinical Studies of Tedizolid To Assess the Potential for Peripheral or Central Monoamine Oxidase Interactions

2013 ◽  
Vol 57 (7) ◽  
pp. 3060-3066 ◽  
Author(s):  
S. Flanagan ◽  
K. Bartizal ◽  
S. L. Minassian ◽  
E. Fang ◽  
P. Prokocimer
Keyword(s):  
Blood Pressure ◽  
Monoamine Oxidase ◽  
Clinical Research ◽  
Systolic Blood Pressure ◽  
Clinical Studies ◽  
Geometric Mean ◽  
Interaction Study ◽  
Mao B ◽  
Mao A

ABSTRACTTedizolid phosphate is a novel oxazolidinone prodrug whose active moiety, tedizolid, has improved potency against Gram-positive pathogens and pharmacokinetics, allowing once-daily administration. Given linezolid warnings for drug-drug and drug-food interactions mediated by monoamine oxidase (MAO) inhibition, including sporadic serotonergic toxicity, these studies evaluated tedizolid for potential MAO interactions.In vitro, tedizolid and linezolid were reversible inhibitors of human MAO-A and MAO-B; the 50% inhibitory concentration (IC50) for tedizolid was 8.7 μM for MAO-A and 5.7 μM for MAO-B and 46.0 and 2.1 μM, respectively, with linezolid. Tedizolid phosphate was negative in the mouse head twitch model of serotonergic activity. Two randomized placebo-controlled crossover clinical studies assessed the potential of 200 mg/day tedizolid phosphate (at steady state) to enhance pressor responses to coadministered oral tyramine or pseudoephedrine. Sensitivity to tyramine was determined by comparing the concentration of tyramine required to elicit a ≥30-mmHg increase in systolic blood pressure (TYR30) when administered with placebo versus tedizolid phosphate. The geometric mean tyramine sensitivity ratio (placebo TYR30/tedizolid phosphate TYR30) was 1.33; a ratio of ≥2 is considered clinically relevant. In the pseudoephedrine study, mean maximum systolic blood pressure was not significantly different when pseudoephedrine was coadministered with tedizolid phosphate versus placebo. In summary, tedizolid is a weak, reversible inhibitor of MAO-A and MAO-Bin vitro. Provocative testing in humans and animal models failed to uncover significant signals that would suggest potential for hypertensive or serotonergic adverse consequences at the therapeutic dose of tedizolid phosphate. Clinical studies are registered atwww.clinicaltrials.govas NCT01539473 (tyramine interaction study conducted at Covance Clinical Research Center, Evansville, IN) and NCT01577459 (pseudoephedrine interaction study conducted at Vince and Associates Clinical Research, Overland Park, KS).

SALIVARY CORTISOL LEVELS TO ESTABLISH A CAUSE AND EFFECT RELATIONSHIP IN PROGRESSION OF ORAL POTENTIALLY MALIGNANT DISORDERS

2021 ◽  
pp. 4-7
Author(s):  
Shefali Shefali ◽  
Saurabh Juneja ◽  
Anshi Jain ◽  
Devi Charan Shetty ◽  
Nikita Gulati
Keyword(s):  
Salivary Cortisol ◽  
Study Groups ◽  
Oral Potentially Malignant Disorders ◽  
Group Iii ◽  
Complex Interactions ◽  
Group I ◽  
Potentially Malignant Disorders ◽  
Potentially Malignant ◽  
Elisa Technique ◽  
Cortisol Levels

The progression and development of OPMDs is inuenced by a multitude of factors which include complex interactions between physiological, psychological, behavioral and social factors. The persistent activation of HPA axis through tobacco usage probably impairs immune response and has a role in progression of OPMDs. The quantication of salivary cortisol facilitates the assessment of nicotine impact on the oral mucosa and in the progression of OPMDs. This study was undertaken to estimate the salivary cortisol levels in the OPMDs with and without habits thereby signifying the importance of salivary cortisol in the causation of disease or as an effective biomarker for disease progression during the pathogenetic process of the disease. Salivary cortisol levels were estimated by ELISA technique in 29 cases of differing grades of oral potentially malignant disorders consisting of individuals with habit and lesions (Group I), 32 cases of individuals having habit without lesions (Group II) and 3 cases of individuals having lesion without habit (Group III) and 8 cases with neither habit nor lesions (Group IV). Salivary cortisol levels were correlated within the different study groups and were analyzed using SPSS (version 20). Salivary cortisol levels were raised in group I as compared to all other groups. Clarity in the present study has been achieved that salivary cortisol levels can be researched to the causation of the disease as an important step forward. This study could open up newer avenues in understanding the pathogenetic mechanisms in Oral Potentially malignant disorders.

scholarly journals Scope of Conventional and Fractal Morphometry in Oral Potentially Malignant Disorders and Oral Cancer

2021 ◽  
Vol 10 (6) ◽  
Author(s):  
Paresh Kumar Behera ◽  
Diksha Mohapatra
Keyword(s):  
Image Analysis ◽  
Fractal Dimension ◽  
Oral Cancer ◽  
World Health ◽  
Oral Potentially Malignant Disorders ◽  
Potentially Malignant Disorders ◽  
Risk Of Malignancy ◽  
Potentially Malignant ◽  
Health Organization

World Health Organization (WHO) defined the terminology ‘Oral Potentially malignant disorders’ (OPMD) as the presence of risk of malignancy in a lesion or condition either during the time of initial diagnosis or at a future date with the commonly accepted prevalence of 1–5%. All OPMDs may not transform into malignancy, many factors have been explored which effectively assess the risk of malignant transformation in OPMDs including many clinical, pathological and molecular factors. Qualitative & experimental factors of different cells in cytological preparations and/or biopsy specimens are reliable parameters for pathologists. The analysis and assessment of histological units can be enhanced by image analysis assisted by a computer that can be used for statistical comparisons. Fractal geometry is considered to be an ideal method of image analysis in quantitative microscopy & histopathology. Fractal dimension analysis is not only limited to determining cell and tumour types but can also be used for determining cellular behaviours in vitro such as cell migration, apoptosis and cellular differentiation, which can be a useful characterization of oral cancer lines and further help in the treatment planning. Keywords: Oral Cancer, Oral Potentially Malignant Disorders (OPMDs), Conventional morphometry, Fractal Dimension, Photomicrograph

scholarly journals ORAL POTENTIALLY MALIGNANT DISORDERS ASSOCIATED WITH BETEL QUID CHEWING HABIT IN SAMOSIR ISLAND, NORTH SUMATRA INDONESIA

2017 ◽  
Vol 20 (2) ◽  
pp. 72-79
Author(s):  
Indri Lubis ◽  
Ameta Primasari ◽  
Sayuti Hasibuan
Keyword(s):  
Health Centre ◽  
Betel Quid ◽  
Control Group ◽  
Oral Potentially Malignant Disorders ◽  
Public Health Centre ◽  
Increased Risk ◽  
Betel Quid Chewing ◽  
Potentially Malignant Disorders ◽  
Potentially Malignant ◽  
North Sumatra

Oral potentially malignant disorders have been associated with a betel quid chewing habit. To date, betel quid chewing has a major social and cultural role in the society of Samosir Island, North Sumatra, Indonesia. The purpose of the present study was to evaluate the occurrence of oral potentially malignant disorders associated with the habit of betel quid chewing in the society of Samosir Island, North Sumatra, Indonesia. This case-control study was conducted on all betel quid chewers in the working area of the Ambarita Public Health Centre in Samosir Regency, North Sumatra, Indonesia. All subjects were examined clinically for the presence of any oral lesions and interviewed for their betel quid chewing habit. Chi-square and Fisher’s exact tests were used to analyze the relationship between variables. Among the 51 subjects recruited in the study, 28 subjects suffered from oral potentially malignant disorders who had oral potentially malignant disorders such as submucous fibrosis and/or leukoplakia (the case group) whereas 23 subjects showed no clinically detectable oral potentially malignant disorders (the control group). An increased risk of oral potentially malignant disorders was associated with the habit of chewing areca nut and tobacco (OR=1.600; p=0.542), the duration of betel quid chewing more than 25 years (OR=4.379; p=0.023), and the frequency of betel quid chewing more than 6 times/day (OR=4.800; p=0.021). In conclusion, oral potentially malignant disorders were associated with chewing betel quid habit in the society of Samosir Island, North Sumatra, Indonesia.

scholarly journals Monoamine Oxidase Inhibitory Activity of Biflavonoids from Branches of Garcinia gardneriana (Clusiaceae)

2017 ◽  
Vol 12 (4) ◽  
pp. 1934578X1701200 ◽  
Author(s):  
Maria Angélica Recalde-Gil ◽  
Luiz Carlos Klein-Júnior ◽  
Carolina dos Santos Passos ◽  
Juliana Salton ◽  
Sérgio Augusto de Loreto Bordignon ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Inhibitory Activity ◽  
Ethanol Extract ◽  
Ethyl Acetate Fraction ◽  
Spectrometric Data ◽  
Mao B ◽  
Inhibitory Compounds ◽  
Mao A ◽  
Mao Activity

Garcinia gardneriana is chemically characterized by the presence of biflavonoids. Taking into account that flavonoids are able to inhibit monoamine oxidase (MAO) activity, in the present study, the chemical composition of the branches’ extract of the plant is described for the first time and the MAO inhibitory activity of the isolated biflavonoids was evaluated. Based on spectroscopic and spectrometric data, it was possible to identify volkesiflavone, morelloflavone (1), Gb-2a (2) and Gb-2a-7- O-glucoside (3) in the ethyl acetate fraction from ethanol extract of the branches. Compounds 1-3 were evaluated in vitro and demonstrated the capacity to inhibit MAO-A activity with an IC50 ranging from 5.05 to 10.7 μM, and from 20.7 to 66.2 μM for MAO-B. These inhibitions corroborate with previous IC50 obtained for monomeric flavonoids, with a higher selectivity for MAO-A isoform. The obtained results indicate that biflavonoids might be promising structures for the identification of new MAO inhibitory compounds.

scholarly journals Design, synthesis, molecular modelling and in vitro screening of monoamine oxidase inhibitory activities of novel quinazolyl hydrazine derivatives

2020 ◽  
Vol 7 (4) ◽  
pp. 200050
Author(s):  
Adel Amer ◽  
Abdelrahman H. Hegazi ◽  
Mohammed Khalil Alshekh ◽  
Hany E. A. Ahmed ◽  
Saied M. Soliman ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Monoamine Oxidase ◽  
In Vitro Screening ◽  
Phenyl Substituent ◽  
Design Synthesis ◽  
Mao B ◽  
Mao A ◽  
Ft Ir ◽  
Inhibitory Activities

A new series of N'-substituted benzylidene-2-(4-oxo-2-phenyl-1,4-dihydroquinazolin-3(2H)-yl)acetohydrazide ( 5a–5h ) has been synthesized, characterized by FT-IR, NMR spectroscopy and mass spectrometry and tested against human monoamine oxidase (MAO) A and B. Only (4-hydroxy-3-methoxybenzylidene) substituted compounds gave submicromolar inhibition of MAO-A and MAO-B. Changing the phenyl substituent to methyl on the unsaturated quinazoline ring ( 12a–12d ) decreased inhibition, but a less flexible linker ( 14a–14d ) resulted in selective micromolar inhibition of hMAO-B providing insight for ongoing design.

scholarly journals Expression of a Splice Variant of CYP26B1 in Betel Quid-Related Oral Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Ping-Ho Chen ◽  
Ka-Wo Lee ◽  
Cheng-Chieh Hsu ◽  
Jeff Yi-Fu Chen ◽  
Yan-Hsiung Wang ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Splice Variant ◽  
Full Length ◽  
Betel Quid ◽  
Human Gingival Fibroblast ◽  
Cancer Tissue ◽  
Gingival Fibroblast ◽  
Dependent Manner ◽  
Pharyngeal Cancer ◽  
Oral And Pharyngeal Cancer

Betel quid (BQ) is a psychostimulant, an addictive substance, and a group 1 carcinogen that exhibits the potential to induce adverse health effects. Approximately, 600 million users chew a variety of BQ. Areca nut (AN) is a necessary ingredient in BQ products. Arecoline is the primary alkaloid in the AN and can be metabolized through the cytochrome P450 (CYP) superfamily by inducing reactive oxygen species (ROS) production. Full-length CYP26B1 is related to the development of oral pharyngeal cancers. We investigated whether a splice variant of CYP26B1 is associated with the occurrence of ROS related oral and pharyngeal cancer. Cytotoxicity assays were used to measure the effects of arecoline on cell viability in a dose-dependent manner.In vitroandin vivostudies were conducted to evaluate the expression of the CYP26B1 splice variant. The CYP26B1 splice variant exhibited lower expression than did full-length CYP26B1 in the human gingival fibroblast-1 and Ca9-22 cell models. Increased expression of the CYP26B1 splice variant was observed in human oral cancer tissue compared with adjacent normal tissue, and increased expression was observed in patients at a late tumor stage. Our results suggested that the CYP26B1 splice variant is associated with the occurrence of BQ-related oral cancer.

Brain monoamine oxidase A in hyperammonemia is regulated by NMDA receptors

2009 ◽  
Vol 4 (3) ◽  
pp. 321-326
Author(s):  
Elena Kosenko ◽  
Yury Kaminsky
Keyword(s):  
Oxidative Stress ◽  
Nmda Receptor ◽  
Monoamine Oxidase ◽  
Nmda Receptors ◽  
Monoamine Oxidase A ◽  
Mk 801 ◽  
Mao A ◽  
Vitro Effect

AbstractMitochondrial enzyme monoamine oxidase A (MAO-A) generates hydrogen peroxide (H2O2) and is up-regulated by Ca2+ and presumably by ammonia. We hypothesized that MAO-A may be under the control of NMDA receptors in hyperammonemia. In this work, the in vivo effects of single dosing with ammonia and NMDA receptor antagonist MK-801 and the in vitro effect of Ca2+ on MAO-A activity in isolated rat brain mitochondria were studied employing enzymatic procedure. Intraperitoneal injection of rats with ammonia led to an increase in MAO-A activity in mitochondria indicating excessive H2O2 generation. Calcium added to isolated mitochondria stimulated MAO-A activity by as much as 84%. MK-801 prevented the in vivo effect of ammonia, implying that MAO-A activation in hyperammonemia is mediated by NMDA receptors. These data support the conclusion that brain mitochondrial MAO-A is regulated by the function of NMDA receptors. The enzyme can contribute to the oxidative stress associated with hyperammonemic conditions such as encephalopathy and Alzheimer’s disease. The attenuation of the oxidative stress highlights MAO-A inactivation and NMDA receptor antagonists as sources of novel avenues in the treatment of mental disorders.

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