Developmental toxicity of arecoline, the major alkaloid in betel nuts, in zebrafish embryos

Chang, Bei‐En; Liao, Mei-Hui; Kuo, Mark Yen‐Ping; Chen, Chi-Hsiang

doi:10.1002/bdra.10136

Cited by 35 publications

(23 citation statements)

References 54 publications

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“…Arecoline-treated embryos exhibited general developmental retardation. By using RT-PCR, in situ hybridization, and antioxidant-protection experiments, Chang et al (2004) indicated that the mechanism underlying growth retardation by arecoline in embryos is predominately due to a general cytotoxic effect induced by depletion of intracellular thiols. Besides, a study by Hung et al (2011) demonstrated that, in human umbilical vein endothelial cells (HUVECs), arecoline stimulated the production of ROS and expressions of ICAM and VCAM.…”

Section: Toxicologymentioning

confidence: 99%

The pharmacology, toxicology and potential applications of arecoline: a review

Liu

Peng

et al. 2016

Pharmaceutical Biology

115

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Context: Arecoline is an effective constituent of Areca catechu L. (Arecaceae) with various pharmacological effects. However, investigations also revealed that long use of arecoline could arouse some oral diseases. Objective: The present review gathers the fragmented information available in the literature (before 1 October 2015) regarding pharmacology and toxicology of arecoline. We also discussed the potential developments and applications of arecoline in the future. Methods: All the available information regarding the arecoline is compiled from scientific databases, including Science Direct, PubMed, Web of Science, Scopus, etc. Results: Previous research demonstrated that arecoline is one of the major effective constituents in A. catechu. Additionally, arecoline has a wide spectrum of pharmacological activities including effects on nervous, cardiovascular, digestive and endocrine systems and anti-parasitic effects. What's more, arecoline is reported to be the primary toxic constituent of A. catechu, and the main toxic effects include oral submucous fibrosis (OSF), oral squamous cell carcinoma (OSCC) and genotoxicity. Conclusion: Arecoline has great potential to be a therapeutic drug for various ailments. However, further investigations are needed in the future to reduce or eliminate its toxicities before developing into new drug. ARTICLE HISTORY

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Section: Toxicologymentioning

confidence: 99%

The pharmacology, toxicology and potential applications of arecoline: a review

Liu

Peng

et al. 2016

Pharmaceutical Biology

115

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“…1, 2, 26–28 This discrepancy can be due to the analyses of raw areca nut in earlier studies and the fact that the total amount and composition of alkaloids varies with the age of areca fruit. For instance, arecoline levels in the nut rise during the maturation period but drop significantly in the matured nut.…”

Section: Resultsmentioning

confidence: 97%

Analysis of Alkaloids in Areca Nut-Containing Products by Liquid Chromatography–Tandem Mass Spectrometry

Jain

Garg

Parascandola

et al. 2017

J. Agric. Food Chem.

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Chewing of areca nut in different forms, such as betel quid or commercially-produced pan masala and gutkha, is common practice in the Indian subcontinent and many parts of Asia, and is associated with a variety of negative health outcomes, particularly oral and esophageal cancers. Areca nut-specific alkaloids arecoline, arecaidine, guvacoline, and guvacine have been implicated in both the abuse liability and the carcinogenicity of areca nut. Therefore, variations in the levels of areca alkaloids could potentially contribute to variations in addictive and carcinogenic potential across areca nut-containing products. Here, we have developed an accurate and robust liquid chromatography-tandem mass-spectrometry (LC-MS/MS) method for simultaneous quantitation of all four areca alkaloids and applied this method to the analysis of a range of products obtained from India, China, and USA. The results of the analyses revealed substantial variations in the levels of alkaloids across the tested products, with guvacine being the most abundant (1.39-8.16 mg/g), followed by arecoline (0.64-2.22 mg/g), arecaidine (0.14-1.70 mg/g) and guvacoline (0.17-0.99 mg/g). Substantial differences in the relative contribution of individual alkaloids to the total alkaloid content were also observed among the different products. Our results highlight the need for systematic surveillance of constituent levels in areca nut-containing products and better understanding of the relationship between the chemical profile and the harmful potential of these products.

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“…Currently, the zebrafish embryo model is being utilized extensively (e.g., Oberemm et al, 1997;Papendorf et al, 1997;Chang et al, 2004;Lefebvre et al, 2004;see Teraoka et al, 2003) to identify developmental toxicity of sublethal doses of naturally occurring toxins. However, in this case, although lower concentrations of the pahayokolide A produced lower numbers of dead embryos, no specific or consistent effect on embryo development, such as morphological malformation or apparent dysfunction of developmental processes, were observed.…”

Section: Discussionmentioning

confidence: 99%

Pharmacology and toxicology of pahayokolide A, a bioactive metabolite from a freshwater species of Lyngbya isolated from the Florida Everglades

Berry

Gantar

Gawley

et al. 2004

Comparative Biochemistry and Physiology Part C: Toxicology &

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The genus of filamentous cyanobacteria, Lyngbya, has been found to be a rich source of bioactive metabolites. However, identification of such compounds from Lyngbya has largely focused on a few marine representatives. Here, we report on the pharmacology and toxicology of pahayokolide A from a freshwater isolate, Lyngbya sp. strain 15−2, from the Florida Everglades. Specifically, we investigated inhibition of microbial representatives and mammalian cell lines, as well as toxicity of the compound to both invertebrate and vertebrate models. Pahayokolide A inhibited representatives of Bacillus, as well as the yeast, Saccharomyces cerevisiae. Interestingly, the compound also inhibited several representatives of green algae that were also isolated from the Everglades. Pahayokolide A was shown to inhibit a number of cancer cell lines over a range of concentrations (IC 50 varied from 2.13 to 44.57 μM) depending on the cell-type. When tested against brine shrimp, pahayokolide was only marginally toxic at the highest concentrations tested (1 mg/mL). The compound was, however, acutely toxic to zebrafish embryos (LC 50 =2.15 μM). Possible biomedical and environmental health aspects of the pahayokolides remain to be investigated; however, the identification of bioactive metabolites such as these demonstrates the potential of the Florida Everglades as source of new toxins and drugs.

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Developmental toxicity of arecoline, the major alkaloid in betel nuts, in zebrafish embryos

Cited by 35 publications

References 54 publications

The pharmacology, toxicology and potential applications of arecoline: a review

The pharmacology, toxicology and potential applications of arecoline: a review

Analysis of Alkaloids in Areca Nut-Containing Products by Liquid Chromatography–Tandem Mass Spectrometry

Pharmacology and toxicology of pahayokolide A, a bioactive metabolite from a freshwater species of Lyngbya isolated from the Florida Everglades

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