Showing papers on "Arecoline published in 2016"

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

Abstract: 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 so...

Areca nut components stimulate ADAM17, IL-1α, PGE2 and 8-isoprostane production in oral keratinocyte: role of reactive oxygen species, EGF and JAK signaling.

Abstract: Betel quid (BQ) chewing is an etiologic factor of oral submucous fibrosis (OSF) and oral cancer. There are 600 million BQ chewers worldwide. The mechanisms for the toxic and inflammatory responses of BQ are unclear. In this study, both areca nut (AN) extract (ANE) and arecoline stimulated epidermal growth factor (EGF) and interleukin-1α (IL-1α) production of gingival keratinocytes (GKs), whereas only ANE can stimulate a disintegrin and metalloproteinase 17 (ADAM17), prostaglandin E2 (PGE2) and 8-isoprostane production. ANE-induced EGF production was inhibited by catalase. Addition of anti-EGF neutralizing antibody attenuated ANE-induced cyclooxygenase-2 (COX-2), mature ADAM9 expression and PGE2 and 8-isoprostane production. ANE-induced IL-1α production was inhibited by catalase, anti-EGF antibody, PD153035 (EGF receptor antagonist) and U0126 (MEK inhibitor) but not by α-naphthoflavone (cytochrome p450-1A1 inhibitor). ANE-induced ADAM17 production was inhibited by pp2 (Src inhibitor), U0126, α-naphthoflavone and aspirin. AG490 (JAK inhibitor) prevented ANE-stimulated ADAM17, IL-1α, PGE2 production, COX-2 expression, ADAM9 maturation, and the ANE-induced decline in keratin 5 and 14, but showed little effect on cdc2 expression and EGF production. Moreover, ANE-induced 8-isoprostane production by GKs was inhibited by catalase, anti-EGF antibody, AG490, pp2, U0126, α-naphthoflavone, Zinc protoporphyrin (ZnPP) and aspirin. These results indicate that AN components may involve in BQ-induced oral cancer by induction of reactive oxygen species, EGF/EGFR, IL-1α, ADAMs, JAK, Src, MEK/ERK, CYP1A1, and COX signaling pathways, and the aberration of cell cycle and differentiation. Various blockers against ROS, EGF, IL-1α, ADAM, JAK, Src, MEK, CYP1A1, and COX can be used for prevention or treatment of BQ chewing-related diseases.

Acquisition cancer stemness, mesenchymal transdifferentiation, and chemoresistance properties by chronic exposure of oral epithelial cells to arecoline.

Abstract: // Tung Yuan Wang 1, * , Chih-Yu Peng 1, 2, * , Shiuan-Shinn Lee 4 , Ming-Yung Chou 1, 2, 3 , Cheng-Chia Yu 1, 2, 3 , Yu-Chao Chang 1, 2 1 School of Dentistry, Chung Shan Medical University, Taichung, Taiwan 2 Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan 3 Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan 4 School of Public Health, Chung Shan Medical University, Taichung, Taiwan * These authors contributed equally to this work Correspondence to: Cheng-Chia Yu, email: ccyu@csmu.edu.tw Yu-Chao Chang, email: cyc@csmu.edu.tw Keywords: arecoline, cancer stemness, oral squamous cell carcinomas Received: November 09, 2015 Accepted: August 13, 2016 Published: August 20, 2016 ABSTRACT Oral squamous cell carcinoma (OSCC), one of the most deadliest malignancies in the world, is caused primarily by areca nut chewing in Southeast Asia. The mechanisms by which areca nut participates in OSCC tumorigenesis are not well understood. In this study, we investigated the effects of low dose long-term arecoline (10 μg/mL, 90-days), a major areca nut alkaloid, on enhancement cancer stemness of human oral epithelial (OE) cells. OE cells with chronic arecoline exposure resulted in increased ALDH1 population, CD44 positivity, stemness-related transcription factors (Oct4, Nanog, and Sox2), epithelial-mesenchymal transdifferentiation (EMT) traits, chemoresistance, migration/invasiveness/anchorage independent growth and in vivo tumor growth as compared to their untreated controls. Mechanistically, ectopic miR-145 over-expression in chronic arecoline-exposed OE (AOE) cells inhibited the cancer stemness and xenografic. In AOE cells, luciferase reporter assays further revealed that miR-145 directly targets the 3′ UTR regions of Oct4 and Sox2 and overexpression of Sox2/Oct4 effectively reversed miR-145-regulated cancer stemness-associated phenomenas. Additionally, clinical results further revealed that Sox2 and Oct4 expression was inversely correlated with miR-145 in the tissues of areca quid chewing-associated OSCC patients. This study hence attempts to provide novel insight into areca nut-induced oral carcinogenesis and new intervention for the treatment of OSCC patients, especially in areca nut users.

Proteomics Analysis Reveals Involvement of Krt17 in Areca Nut-Induced Oral Carcinogenesis.

Abstract: The areca nut is a known carcinogen that causes oral cancer in individuals in Southeast Asia, but the molecular mechanism that leads to this malignancy is still unclear. To mimic the habit of areca nut chewing, our laboratory has established four oral cancer cell sublines (SAS, OECM1, K2, C9), which have been chronically exposed to areca nut extract (ANE). To elucidate the molecular basis of areca nut-induced oral carcinogenesis, the differential proteomes between oral cancer cells and the ANE-treated sublines were determined using isobaric mass tag (iTRAQ) labeling and multidimensional liquid chromatography-mass spectrometry (LC-MS/MS). Over 1000 proteins were identified in four sublines, and 196 proteins were found to be differentially expressed in at least two ANE-treated sublines. A bioinformatic analysis revealed that these proteins participate in several pathways, and one of the most prominent pathways was the regulation of epithelial to mesenchymal transition (EMT). In all, 24 proteins including Krt17 were confirmed to be differentially expressed in the ANE-treated sublines. To reveal additional information on the mechanism of ANE-induced carcinogenesis, Krt17 was further investigated. Krt17 knockdown significantly suppressed ANE-induced cell migration and invasion and modulated the EMT process. Furthermore, in a murine model of carcinogen-induced (arecoline cocktail, an active compound of ANE) oral cancer, Krt17 was significantly up-regulated in all hyperplastic tissues and in carcinoma tissues (p < 0.001). In conclusion, we have identified a proteome of oral cancer cells that is associated with chronic areca nut exposure. Krt17 was demonstrated to contribute to areca nut-induced oral malignancy. The results of this study contribute to risk assessment, disease prevention and other clinical applications associated with areca nut-induced oral cancer.

Areca nut alkaloids induce irreparable DNA damage and senescence in fibroblasts and may create a favourable environment for tumour progression.

Abstract: Background Oral submucous fibrosis (OSMF) is a pre-malignant condition that is strongly associated with the areca nut alkaloids, arecoline (ARC) and arecaidine (ARD). The condition is characterised by the presence of senescent fibroblasts in the subepithelial mesenchyme which have the potential to promote malignancy in the neighbouring epithelial cells. We tested the hypothesis that areca nut alkaloids induce senescence in oral fibroblasts and promote the secretion of invasion-promoting transforming growth factor β (TGF-β) and matrix metalloproteinase-2 (MMP-2). Methods Two oral fibroblast lines were treated for 48h with ARC and ARD. Senescence-associated β-galactosidase (SA-βGal) activity, Ki67 (cycling cells), large 53BP1 foci (irreparable DNA strand breaks) and p16INK4A (late senescence) were used as markers of cellular senescence and were quantified using indirect immunofluorescence and the ImageJ program. TGF-β and MMP-2 levels were measured using ELISA. Statistical analyses were performed with the two-tailed unpaired t-test where n = 3 and the Wilcoxon–Mann–Whitney test where n = 6. Results ARC (100 and 300 μM) and ARD (30 and 100 μM) significantly (P < 0.05) induced fibroblast senescence, as determined by the increased expression of SA-βGal, 53BP1 staining and CDKN2A/p16INK4A; there was also a non-significant reduction in Ki67 staining. Treated cells also showed a three- fivefold increase in TGF-β and a small non-significant increase in MMP-2. Conclusions Areca nut alkaloids induce senescence in oral fibroblasts and promote increased secretion of TGF-β and perhaps MMP-2 that may create a tissue environment thought to be critical in the progression of OSMF to malignancy.

Pilot study of the pharmacokinetics of betel nut and betel quid biomarkers in saliva, urine, and hair of betel consumers

Abstract: Approximately 600 million people worldwide practise the carcinogenic habit of betel nut/quid chewing. Carcinogenic N-nitroso compounds have been identified in saliva or urine of betel chewers and the betel alkaloid arecoline in hair from habitual betel quid chewers. However, the pharmacokinetic parameters of these compounds have been little explored. Assessment of betel use by biomarkers is urgently needed to evaluate the effectiveness of cessation programmes aimed at reducing betel consumption to decrease the burden of cancers in regions of high betel consumption. In the search for biomarkers of betel consumption, we measured by liquid chromatography-mass spectrometry (LC-MS) the appearance and disappearance of betel alkaloids (characteristic for betel nuts), N-nitroso compounds, and chavibetol (characteristic for Piper Betle leaves) in saliva (n=4), hair (n=2), and urine (n=1) of occasional betel nut/quid chewers. The betel alkaloids arecoline, guvacoline, guvacine, and arecaidine were detected in saliva of all four participants and peaked within the first 2 h post-chewing before returning to baseline levels after 8 h. Salivary chavibetol was detected in participants consuming Piper Betle leaves in their quid and peaked ~1 h post-chewing. Urinary arecoline, guvacoline, and arecaidine excretion paralleled saliva almost exactly while chavibetol glucuronide excretion paralleled salivary chavibetol. No betel nut related compounds were detected in the tested hair samples using various extraction methods. From these preliminary results, we conclude that betel exposure can only be followed on a short-term basis (≤8 h post-chewing) using the applied biomarkers from urine and saliva while the feasibility of using hair has yet to be validated. Copyright © 2015 John Wiley & Sons, Ltd.

Elevated transglutaminase-2 expression mediates fibrosis in areca quid chewing-associated oral submucocal fibrosis via reactive oxygen species generation

Abstract: Objectives Transglutaminase-2 (TGM-2) protein is involved in the cross-linking of matrix proteins resulting in several fibrotic disorders and can be induced by reactive oxygen species (ROS) Little is known about its role in the development of oral submucocal fibrosis (OSF) Hence, we hypothesize that TGM-2 may have a role in the pathogenesis of areca quid chewing-associated OSF and arecoline, a major areca nut alkaloid, could regulate TGM-2 via ROS generation

Arecoline Induces Neurotoxicity to PC12 Cells: Involvement in ER Stress and Disturbance of Endogenous H2S Generation.

Abstract: Arecoline is a major alkaloid of areca nut and has been effect on central nervous system. Although arecoline-induced neurotoxicity has been reported, the possible underlying neurotoxic mechanisms have not yet been elucidated. Increasing evidences have shown that both excessive endoplasmic reticulum (ER) stress and disturbance of hydrogen sulfide (H2S) production are involved in the pathophysiology of numerous neurodegenerative diseases. Here, the purpose of present study was to verify whether ER stress and the disturbance of endogenous H2S generation are also involved in arecoline-caused neurotoxicity. We found that treatment of PC12 cells with arecoline induced the down-regulation of cells viability and up-regulation of apoptosis and the activity of caspase-3, indicating the neurotoxic role of arecoline to PC12 cells. In addition, arecoline also increased the expression of Bax (pro-apoptotic protein) and attenuated the expression of Bcl-2 (anti-apoptotic protein) in PC12 cells. Simultaneously, arecoline caused excessive ER stress in PC12 cells, as evidenced by the up-regulations of Glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP), and Cleaved caspase-12 expressions. Notably, the level of H2S in the culture supernatant and the expressions of cystathionine β-synthase and 3-mercaptopyruvate sulfurtransferase (two major enzymes for endogenous H2S generation in PC12 cells) were also reduced by arecoline treatment. These results indicate that arecoline-caused neurotoxicity to PC12 cells is involved in ER stress and disturbance of endogenous H2S generation and suggest that the modulation of ER stress and endogenous H2S generation may be potential therapeutic approach in treatment of arecoline-caused neurotoxicity.

Arecoline Alters Taste Bud Cell Morphology, Reduces Body Weight, and Induces Behavioral Preference Changes in Gustatory Discrimination in C57BL/6 Mice

Abstract: Arecoline, a major alkaloid in areca nuts, is involved in the pathogenesis of oral diseases. Mammalian taste buds are the structural unit for detecting taste stimuli in the oral cavity. The effects of arecoline on taste bud morphology are poorly understood. Arecoline was injected intraperitoneally (IP) into C57BL/6 mice twice daily for 1-4 weeks. After arecoline treatment, the vallate papillae were processed for electron microscopy and immunohistochemistry analysis of taste receptor proteins (T1R2, T1R3, T1R1, and T2R) and taste associated proteins (α-gustducin, PLCβ2, and SNAP25). Body weight, food intake and water consumption were recorded. A 2-bottle preference test was also performed. The results demonstrated that 1) arecoline treatment didn't change the number and size of the taste buds or taste bud cells, 2) electron microscopy revealed the change of organelles and the accumulation of autophagosomes in type II cells, 3) immunohistochemistry demonstrated a decrease of taste receptor T1R2- and T1R3-expressing cells, 4) the body weight and food intake were markedly reduced, and 5) the sweet preference behavior was reduced. We concluded that the long-term injection of arecoline alters the morphology of type II taste bud cells, retards the growth of mice, and affects discrimination competencies for sweet tastants.

What Is the ``Areca'' in ``Areca Nuts''? Extraction and Neuroactive Bioassay of Arecoline

Abstract: A series of three practical sessions are designed to give students firsthand experience with the preparation of natural product extracts and assay using a live tissue preparation. Areca or betel nuts are the seeds from the fruit of the Areca catechu palm tree that is known to contain a number of pharmacologically active alkaloids. The principal of these is arecoline that makes up to 1% of the dry nut. Arecoline is a potent spasmogenic agent, causing smooth muscle contraction via muscarinic acetylcholine receptor (mAChR) activation. The first session involves the preparation of methanolic extracts from whole areca nuts and TLC for the qualitative identification of arecoline present in the extract. The second session utilizes the spasmodic effects of arecoline on smooth muscle to allow students to perform a live tissue bioassay using guinea-pig ileum. This response is subsequently blocked by the mAChR antagonist atropine to investigate the mechanism underlying the measured response. The final session gives ...

Oral and Systemic Health Effects of Compulsive Areca Nut Use

Abstract: The areca nut is the fourth most used drug after nicotine, alcohol, and caffeine. Methods of use vary from being chewed alone to being an essential ingredient in a “quid” with tobacco frequently added to the mixture. Arecoline is the main alkaloid in the areca nut and readily crosses the blood–brain barrier. The effects are described as pleasurable and generally stimulating, inducing a sense of well-being, euphoria, heightened alertness, a warm sensation throughout the body, and an increased capacity to work. Adverse health effects range from premalignant and malignant oral lesions to vascular and neurological effects including tachycardia and palpitations, hypotension, sweating, dizziness, coma, and acute myocardial infarction. There is evidence for a dependency state associated with compulsive areca nut use; however, this is often mild. Withdrawal symptoms include: mood swings, anxiety, irritability, reduced concentration, and sleep deprivation. The ability to quit chewing becomes harder as the period of time of chewing and frequency of use increase.

Solid arecoline beverage and preparation method thereof

Abstract: The invention discloses a solid arecoline beverage and a preparation method thereof. The solid arecoline beverage is prepared through blending, granulation and drying from following raw materials in percentage by weight: 0.01%-20% of areca catechu biotin, 0-20% of sugar, 0.1%-20% of a sour agent, 0-20% of polyalcohol, 1%-50% of maltodextrin, 0.01%-0.5% of a taste masking agent and 1%-50% of water. The areca catechu biotin is added to the solid arecoline beverage, multiple nutritional substances, beneficial to a human body, in fresh areca catechu are reserved, and the areca catechu is prepared in a solid beverage form, so that areca catechu consumption is greatly facilitated.

Areca Nut Chewing Complicated with Non-Obstructive and Obstructive ST Elevation Myocardial Infarction.

Abstract: Areca nut chewing is one of the most prevalent substance abuse habits in the world, and it is associated with the risk of a variety of medical challenges including hypertension, arrhythmia, and coronary artery disease (CAD). However, ST elevation myocardial infarction (STEMI) is an extremely rare complication of areca nut chewing. Herein we report two cases where patients suffered from STEMI after areca nut chewing. The first case involved a patient with non-obstructive CAD and non-sustained ventricular tachycardia during hospitalization. The second case revealed left circumflex artery total occlusion, and primary percutaneous coronary interventionwas performed. Initially, the levels of arecoline and arecaidine plasma were checked in these two cases after admission. Although both cases revealed increased levels, the second case showed substantially higher values than the first case. In general, these two cases remind physicians that areca nut chewing may cause myocardial injury with different severity, although STEMI with true coronary obstruction remains an extremely rare but possible complication after areca nut chewing.

General Aspects of Areca Nut Addiction

Abstract: The Areca catechu nut has a long history of consumption throughout the world, especially in South East Asia. It is estimated to be consumed by 20% of the global population. This figure is on the rise due to migration of native users to developed countries. The literature reveals that areca nut consumption is linked to the dependency syndrome and exhibits cross-sensitivity with substances of abuse, such as cigarettes and alcohol. Additionally, its preparation practices and patterns of consumption resemble that of addictive substances, which reflect its liability for addiction. Its alkaloid, that is, arecoline, underlies most biological actions and needs to be explored from an addictive perspective. Preclinical data reveal that the nut's crude fraction inhibited whereas arecoline precipitated morphine-induced withdrawal. The major limitation in the literature is the lack of neurochemical evidence supporting its addictive potential, which needs to be evaluated to protect consumers from its health hazards.

[Effect of arecoline on proliferation and apoptosis of MCF-7 human breast cancer cells].

Abstract: Objective To observe the effects of arecoline on proliferation and apoptosis of MCF-7 human breast cancer cells and to ex-plore its possible mechanism. Methods Human breast cancer MCF-7 cells were treated with arecoline at the concentrations of 0,10,30,50, 100,300,500μmol/L, the cell proliferation were detected by MTT assay, cell apoptosis were analyzed by Hoechst 33342 staining and flow cy-tometry, the protein expression of Bax,Bcl-2 and P53 were detected by Western blot. Results Low concentration(0,10,30, 50 μmol/L) arecoline had no effect on the proliferation and apoptosis of MCF-7. However, high concentration(100,300,500μmol/L) arecoline inhibited proliferation and induced apoptosis of MCF-7 cells in a concentration-dependent manner, arecoline also significantly increased P53 and Bax protein expression and decreased Bcl-2 protein expression. Conclusions High concentration arecoline inhibited the proliferation and induced the apoptosis of MCF-7 cells, the mechanism was probably corrected with increasing P53 and Bax protein expression and decreasing Bcl-2 pro-tein expression.

Permeability characteristics of various types of areca nut preparations in Sprague–Dawley rat oral mucosa

Abstract: Background Oral submucous fibrosis is a potentially malignant oral disorder causatively linked to the habit of areca nut consumption. The various types of preparation of the nut alter the properties and consequently its capability to diffuse through the oral mucosa. Permeability of the nut through the mucosal tissue is an important factor in the production of lesions. Aims The present study attempts to evaluate the permeability of various areca nut preparations standardized against arecoline in the buccal mucosa of Sprague–Dawley rats. Apart from normal mucosal permeability, we also aimed to assess the lesional tissues induced by the application of the areca nut solutions. Materials and methods Healthy in-bred Sprague–Dawley rats aged 3–4 months and weighing 100–200 g were randomly selected and divided into five groups: the control group, the raw areca nut group, the boiled areca nut group, the roasted areca nut group and the pan masala and pure arecoline groups. Permeability was assessed using a Franz diffusion chamber over a period of 24–72 h. Histological assessment to determine depth in the tissue was also done. Results The highest average permeation depths were recorded in the boiled areca nut group (1178.21 μm), followed by the raw areca nut (1157.50 μm), the pan masala (1110.34 μm) and the roasted areca nut (1072.36 μm) groups, as compared with controls (350.79 μm). Overall, there occurred a mild increase in the permeation depths of the solutions in all groups at 72 h compared with 24 h. Statistical analysis revealed that the permeation values had a significant negative correlation with epithelial and keratin thickness. Conclusion There seems to be a time-dependent and solute (areca nut)-dependent pattern in the permeability characteristics. Diffusibility is continuous, persistent and progressive, and tissue reaction in the form of epithelial changes and fibrosis does not appear to be a significant barrier in the process. This study strongly supports the pathological changes seen in the disorders caused by the consumption of areca nut in humans.

Areca nut cataplasm, preparation method and application thereof

Abstract: The invention provides areca nut cataplasm, a preparation method thereof and application thereof in preparing medicine for expelling parasites, resisting depression and refreshing. The areca nut cataplasm has the advantages that medicinal value of areca nut is increased, damage to the oral cavity caused by arecoline is avoided, concentration of blood and intracerebral medicine is improved, and effects, on expelling parasites, resisting depression and refreshing, of areca nut are enhanced.

Arecoline beverage and preparation method thereof

Abstract: The invention discloses an arecoline beverage and a preparation method thereof The arecoline beverage is prepared from the following components in percentage by weight: 001-20% of areca nut biotin, 01-5% of siraitia grosvenorii, 0-5% of honey, 0-10% of sugar, 001-006% of sour materials, 0-5% of polyalcohol, 0-1% of caramel color and the balance being water, and is prepared through the following steps of dissolving, blending, fine filtration, deaeration, sterilization and filling According to the arecoline beverage disclosed by the invention, the areca nut biotin is added, so that varied nutrient substances which are beneficial to human bodies in fresh areca nuts are reserved, then the fresh areca nuts are made in the form of the beverage, the areca nuts are greatly convenient for people to eat, and dual requirements of consumers for the areca nuts and health are met

Evaluation of Histological Changes in the Salivary Glands of Sprague-Dawley rats Following Injections of Various Forms of Areca Nut Preparations

Abstract: Introduction: The habit of areca nut chewing impinges on the daily lives of about one-tenth of the world’s population. Areca nut is used in many forms ranging from raw to commercial varieties. The consumption of areca nut is found to have important effects on salivary glands leading to an altered salivary flow rate and pH of saliva. Areca nut consumption is significantly associated with the development of oral submucous fibrosis (OSF). OSF in the early stages is characterized by an increased salivation and advanced stages by an increased dryness of the oral mucosa. Aims and Objectives: The present study aimed to evaluate the histopathological tissue changes in the rat submandibular salivary glands subjected to various forms of areca nut (raw, roasted, and boiled), pan masala extracts, and pure arecoline solution over a period of 36-week. Materials and Methods: 3-4 months old Sprague-Dawley rats were randomly selected and divided into six groups - Control, raw areca nut, boiled areca nut, roasted areca nut, pan masala, and pure arecoline groups; treated with the respective solutions. The control group was treated with distilled water. Rats were sacrificed randomly at an interval of every 6 weeks and submandibular glands dissected out and assessed for any histological changes. Results: Significant histological changes were observed in the rat submandibular tissues including fusion and dilatation of acini and ducts with pooling of the salivary secretions in the initial weeks of treatment and degenerative changes in the later weeks. Among all the groups, the pure arecoline treated group showed significant and early degenerative changes in comparison to the other groups. Conclusion:Chronic consumption of areca nut in various forms leads to deleterious effects on the salivary gland histology leading to degeneration of acini and ductal structures. This degenerative effect leads to an overall decreased salivary output reflecting as dryness of mucosa in the advanced stages of OSF and probably to a decreased local immunity and hence an increased propensity for malignant transformation in the later stages of OSF.

Processes and methods of manufacture of arecoline

Abstract: Processes and methods of manufacturing an areca fruit product. One process may include the steps of providing a plurality of areca fruits, drying the plurality of areca fruits, dehusking the plurality of areca fruits to obtain a plurality of areca nuts, chopping, shredding or grinding the plurality of areca nuts into a multiplicity of areca nut particles, introducing the multiplicity of areca nut particles into a tank containing water, agitating the multiplicity of areca nut particles to create a slurry, determining an amount of arecoline in the slurry and pumping the water having the predetermined amount of arecoline through a filter and into a holding tank and concentrating the arecoline in an evaporator. Additional steps include fermentation, distillation, pasteurization, and cold pressing of the arecoline to produce a synthetic nicotine and/or botanical pesticide.

Effect of Calcium Channel Blockers on Increased Plasma Testosterone Level Induced by Arecoline in Male Albino Rats

Abstract: Background: Arecoline is one of the major components of betel nuts, which have been consumed as chewing gum in Southeast Asia. Arecoline might affect the endocrine system but the mechanism is still unclear.Some studies suggest that calcium channels may play a role in this effect. Aim: The present study was carried out to investigate the effect of calcium channel blockers on increased plasma testosterone level induced by Arecoline of betel nuts in rats. Methods: 80 male albino rats were divided into 8 equal groups as follows: control group; arecoline group; Human chorionic ganadotropin (HCG) group; arecoline + HCG group; nifedipine group; nifedipine + arecoline group; tetrandrine group and tetrandrine + arecoline group. After 2 hours of injection, rats were sacrificed and blood samples were collected and plasma was separated for determination of testosterone, androstendione and leutinizing hormone (LH). Results: Arecoline with and without HCG resulted in significant increase of plasma testosterone and androsteindione, and only significant increase after HCG injection of LH levels. Injection of nifedipine or tetrandrine alone caused non-significant change in plasma testosterone and androsteindione compared with the control group. Injection of nifedipine or tetrandrine with arecoline resulted in significant reduction in plasma testosterone and androsteindione levels compared with arecoline treated group. Conclusion: Arecoline caused significant increase in testosterone secretion in male albino rats that may be due to calcium channel activation in Leydig cells.