Showing papers on "Arecoline published in 2003"

Roles of keratinocyte inflammation in oral cancer: regulating the prostaglandin E2, interleukin-6 and TNF-α production of oral epithelial cells by areca nut extract and arecoline

Abstract: Betel quid (BQ) chewing is an etiologic factor of oral cancer and submucus fibrosis (OSF). Keratinocyte inflammation is crucial for the pathogenesis of cancer and tissue fibrosis. We found that areca nut (AN) extract (100-400 micro g/ml) induced PGE2 production by KB cells by 2.34- to 23.1-fold and also TNF-alpha production by gingival keratinocytes (GK). Arecoline (0.2-1.2 mM) elevated PGE2 production by KB cells by 2.5- to 6.1-fold. AN extract (200-400 micro g/ml) also induced IL-6 production by GK (7.5- to 8.4-fold) and KB cells. In contrast, arecoline (0.1-1.2 mM) suppressed IL-6 production by GK and KB cells, with 42-81 and 41-63% inhibition, respectively. A 48 h exposure of GK to 800-1200 micro g/ml AN extract led to 37-69% cell death. Arecoline cytotoxicity to GK was noted at concentrations of 0.8-1.2 mM, which led to 28-38% cell death. AN extract (400-800 micro g/ml) induced Cox-2 and IL-6 mRNA expression and also COX-2 protein production by KB cells. IL-6 (5-100 ng/ml) suppressed GK growth by 20-33%, but enhanced oral fibroblast (OMF) and KB cell growth. PGE2 (0.05-5 micro g/ml) and anti-IL-6 antibody (ab) (50-1000 ng/ml) showed little effect on GK and KB cell growth. Incubation of GK and KB cells with aspirin, anti-IL-6 ab and anti-TNF-alpha ab showed little effect on arecoline- and AN-induced cytotoxicity, cell cycle arrest and apoptosis. Exposure to anti-TNF-alpha ab slightly affected arecoline- and AN-modulated PGE2 and IL-6 production by GK and KB cells. Arecoline- and AN-conditioned medium decreased phytohemagglutinin-mediated CD4+ and CD8+ T cell activation. These results indicate that BQ chewing contributes to the pathogenesis of cancer and OSF by impairing T cell activation and by induction of PGE2, TNF-alpha and IL-6 production, which affect oral mucosal inflammation and growth of OMF and oral epithelial cells.

The up-regulation of cyclooxygenase-2 expression in human buccal mucosal fibroblasts by arecoline: a possible role in the pathogenesis of oral submucous fibrosis.

Abstract: Background: Aberrant and persistent tissue inflammation are believed to play an important role on the occurrence of tissue fibrosis. Cyclooxygenase (COX)-2 is an inducible enzyme responsible for prostaglandin synthesis in certain inflammatory diseases. The purpose of this study was to compare COX-2 expression in normal human buccal mucosa and oral submucous fibrosis (OSF) specimens and further explore the potential mechanism that may lead to induce COX-2 expression. Methods: Fifteen OSF specimens and six normal buccal mucosa were examined by immunohistochemistry. Primary human buccal mucosa fibroblasts (BMFs) were established and challenged with arecoline analyzed by reverse transcriptase polymerase chain reaction. Furthermore, to elucidate whether induction of COX-2 is associated with cytotoxicity, aspirin (a non-selective inhibitor of COX enzyme) and NS-398 (a selective COX-2 inhibitor), were added to test their protective effects. Results: COX-2 expression was significantly higher in OSF specimens and expressed mainly by epithelial cells, endothelial cells, and cells with fibroblast morphology. In vitro studies indicated that BMFs did not express COX-2 constitutively. However, when the cells were treated with 80 µg/ml arecoline, COX-2 expression was up-regulated as early as half an hour. This indicates that COX-2 expression is an early cellular response and regulated by arecoline at transcriptional level. In addition, pre-treatment with glutathione (GSH) precursor, 2-oxothiazolidine-4-carboxylic acid (OTZ), led to a decrease in induction of COX-2 mRNA by arecoline. GSH synthesis inhibitor, buthionine sulfoximine (BSO), was found to increase arecoline-induced COX-2 mRNA levels. Moreover, both of aspirin and NS-398 at non-cytotoxic doses are not able to prevent arecoline-induced cytotoxicity. This indicates that arecoline cytotoxicity is not directly via the induction of COX-2 expression. Conclusions: Taken together, these results suggest that COX-2 expression is significantly up-regulated in OSF tissues from areca quid chewers and arecoline may among other constituents be responsible for the enhanced COX-2 expression in vivo. The regulation of COX-2 expression induced by arecoline is critically dependent on the cellular GSH concentration.

Chronic lithium administration potentiates brain arachidonic acid signaling at rest and during cholinergic activation in awake rats

Abstract: Studies were performed to determine if the reported ‘proconvulsant’ action of lithium in rats given cholinergic drugs is related to receptor-initiated phospholipase A2 signaling via arachidonic acid. Regional brain incorporation coefficients k* of intravenously injected [1-14C]arachidonic acid, which represent this signaling, were measured by quantitative autoradiography in unanesthetized rats at baseline and following administration of subconvulsant doses of the cholinergic muscarinic agonist, arecoline. In rats fed LiCl for 6 weeks to produce a therapeutically relevant brain lithium concentration, the mean baseline values of k* in brain auditory and visual areas were significantly greater than in rats fed control diet. Arecoline at doses of 2 and 5 mg/kg intraperitoneally increased k* in widespread brain areas in rats fed the control diet as well as the LiCl diet. However, the arecoline-induced increments often were significantly greater in the LiCl-fed than in the control diet-fed rats. Lithium's elevation of baseline k* in auditory and visual regions may correspond to its ability in humans to increase auditory and visual evoked responses. Additionally, its augmentation of the k* responses to arecoline may underlie its reported ‘proconvulsant’ action with cholinergic drugs, as arachidonic acid and its eicosanoid metabolites can increase neuronal excitability and seizure propagation.

Genotoxic effect of raw betel-nut extract in relation to endogenous glutathione levels and its mechanism of action in mammalian cells.

Abstract: The mutagenic and carcinogenic potency of betel-nut components is well established. This study was undertaken to determine the genotoxic potency of an aqueous extract of raw betel nut (AEBN) in relation to the endogenous glutathione (GSH) level in mouse bone marrow cells (BMC) and human peripheral blood lymphocytes (PBLs), and to find out whether arecoline (ARC), an alkaloid of betel nut, could generate reactive oxygen species (ROS) in these cells. It was observed that AEBN has genotoxic properties, which is further enhanced by depletion of endogenous GSH levels. However, the degree of enhancement varies with the type of parameter and cell system studied. The present data indicate that the generation of ROS by ARC could partially contribute to the induction of chromosomal aberrations (CAs), since the frequency of ARC-induced CAs was reduced either by post-treatment with superoxide dismutase (SOD) or in anoxic conditions. However, the induction of sister chromatid exchanges (SCEs) probably involves p53-dependent changes in cell proliferation and allowing some repair of DNA damage. The extent of damage for each parameter was higher when the mice were exposed to AEBN for 30 days than 5 days. Longer exposure showed higher level of p53 expression in mouse BMC, which could block the damaged cells from proliferation and allow the cells to repair the DNA damage.

Quantification of arecoline (areca nut alkaloid) in neonatal biological matrices by high‐performance liquid chromatography/electrospray quadrupole mass spectrometry

Abstract: A high-performance liquid chromatography (HPLC) method with mass spectrometric detection is described for determination of arecoline in newborn meconium, urine and cord serum, using pilocarpine as internal standard. The analytes were extracted from neonatal biological matrices with chloroform/isopropanol (95:5, v/v) at alkaline pH. Extracts were analyzed by HPLC coupled to an electrospray (ESI) interface and a quadrupole mass spectrometer. Chromatography was performed on a C8 reversed-phase column using 10 mM ammonium acetate (pH 4.3)/acetonitrile (90:10, v/v) as mobile phase. The mass spectrometer was operated in selected ion monitoring mode. The method was validated over the concentration range 0.005–1.00 μg/g meconium, 0.004–1.00 μg/mL cord serum and 0.001–1.00 μg/mL urine. Mean recoveries ranged between 86.5 and 90.7% for arecoline in the different biological matrices, with precision always better than 10%. The quantification limits of arecoline were 0.005 μg/g meconium, 0.004 μg/mL cord serum, and 0.001 μg/mL urine. The method was applied to the analysis of neonatal biological matrices to assess eventual fetal exposition to arecoline. Two newborns from Asian mothers who declared areca nut consumption presented arecoline in meconium with concentrations in the range 0.006–0.008 μg/g; also the urine from one neonate tested positive for the drug. Copyright © 2003 John Wiley & Sons, Ltd.

Areca nut, energy metabolism and hunger in Asian men

Abstract: Background : The nut of the Areca catechu palm has long been attributed effects on hunger and the digestive process. Objectives : The objectives were to assess experimentally effects of areca nut on fasting and postprandial energy metabolism, substrate utilization and hunger. Subjects and methods : Two randomized, placebo-controlled, double-blind studies were undertaken. In study 1, eight Indian men received bioadhesive gels delivering 0, 5, 10 or 20 mg arecoline to the buccal sulcus after an overnight fast. Resting energy expenditure and substrate utilization were determined by ventilated hood calorimetry over 6 h during which hunger was rated on five occasions. In study 2, 15 Indian men received gels delivering 0 or 10 mg arecoline after consuming a 2.5 MJ meal, and the same protocol was then applied as in study 1. Results : Fasting resting energy expenditures exceeded basal metabolic rate (BMR) by 5.4 - 0.8% (Mean - SE) after placebo, and 5.1 - 0.7% after 20 mg arecoline, but by 0.9 - 0.8% ...

Composition for skin whitening containing Arecoline

Abstract: PURPOSE: A skin whitening composition containing, as an active ingredient, arecoline capable of being obtained from Areca catechu L. is provided. The composition prevents pigmentation by inhibiting the formation of melamine without adverse effect and is thus effective for skin whitening or improvement of chloasma or freckles. CONSTITUTION: The skin whitening composition contains 0.000001 to 10% by weight of arecoline(1,2,5,6-tetrahydro-1-methyl-3-pyridinecarboxylic acid methyl ester) of the formula(1) commonly known as an agent for treating disorders caused by cerebral ischemia including stroke, alcohol craving, decreased memory function etc., based on the total weight of the composition. The arecoline is obtained by extracting Areca catechu L. in a solvent selected from the group consisting of C1-4 lower alcohol, ethyl acetate, acetone, ether, benzene, chloroform, hexane, cyclohexane and petroleum ether.