Showing papers on "Arecoline published in 2006"

A metabolomic approach to the metabolism of the areca nut alkaloids arecoline and arecaidine in the mouse.

Abstract: The areca alkaloids comprise arecoline, arecaidine, guvacoline, and guvacine. Approximately 600 million users of areca nut products, for example, betel quid chewers, are exposed to these alkaloids, principally arecoline and arecaidine. Metabolism of arecoline (20 mg/kg p.o. and i.p.) and arecaidine (20 mg/kg p.o. and i.p.) was investigated in the mouse using a metabolomic approach employing ultra-performance liquid chromatography-time-of-flight mass spectrometric analysis of urines. Eleven metabolites of arecoline were identified, including arecaidine, arecoline N-oxide, arecaidine N-oxide, N-methylnipecotic acid, N-methylnipecotylglycine, arecaidinylglycine, arecaidinylglycerol, arecaidine mercapturic acid, arecoline mercapturic acid, and arecoline N-oxide mercapturic acid, together with nine unidentified metabolites. Arecaidine shared six of these metabolites with arecoline. Unchanged arecoline comprised 0.3-0.4%, arecaidine 7.1-13.1%, arecoline N-oxide 7.4-19.0%, and N-methylnipecotic acid 13.5-30.3% of the dose excreted in 0-12 h urine after arecoline administration. Unchanged arecaidine comprised 15.1-23.0%, and N-methylnipecotic acid 14.8%-37.7% of the dose excreted in 0-12 h urine after arecaidine administration. The major metabolite of both arecoline and arecaidine, N-methylnipecotic acid, is a novel metabolite arising from carbon-carbon double-bond reduction. Another unusual metabolite found was the monoacylglyceride of arecaidine. What role, if any, that is played by these uncommon metabolites in the toxicology of arecoline and arecaidine is not known. However, the enhanced understanding of the metabolic transformation of arecoline and arecaidine should contribute to further research into the clinical toxicology of the areca alkaloids.

Genetic damage in cultured human keratinocytes stressed by long-term exposure to areca nut extracts.

Abstract: Chewing betel quid (BQ) is a popular habit worldwide A causal association between BQ chewing and oral cancer has been well documented Emerging evidence indicates that sustained exposure to stress induces epigenetic reprogramming of some mammalian cells and increases the mutation rate to accelerate adaptation to stressful environments In this study, we first confirmed that 24-h treatment with areca nut extracts (ANE; a major component of BQ) at doses over 40 μg/ml induced mutations at the hypoxanthine phosphoribisyltransferase ( HPRT ) locus in human keratinocytes (HaCaT cells) We then investigated whether the stress of long-term exposure to sublethal doses of ANE (0, 5 and 20 μg/ml for 35 passages) could enhance genetic damage to HaCaT cells Compared to cells exposed to 0 or 5 μg/ml ANE, cells exposed to 20 μg/ml ANE were slightly but significantly more resistant to a 72-h treatment with ANE and its major ingredients, arecoline and arecaidine, but did not develop cross-resistance to other BQ ingredients or alcohol The cells that received 20 μg/ml ANE for 35 passages also had a significantly increased mutation frequency at the HPRT locus and an increased frequency in the appearance of micronuclei compared to lower doses Moreover, increased intracellular levels of reactive oxygen species and 8-hydroxyguanosine in cells exposed to 20 μg/ml ANE suggested that long-term ANE exposure results in the accumulation of oxidative damage However, cells subjected to long-term treatment of 20 μg/ml ANE contained higher levels of glutathione than unexposed cells Therefore, after long-term exposure to sublethal doses of ANE, intracellular antioxidative activity may also be enhanced in response to increased oxidative stress These results suggest that stress caused by long-term ANE exposure enhances oxidative stress and genetic damage in human keratinocytes

Areca-Nut Abuse and Neonatal Withdrawal Syndrome

Abstract: Areca-nut chewing occurs widely in South Asia and the Indian subcontinent. Here we present a case of neonatal withdrawal syndrome in an infant born to a woman who was a chronic areca-nut user. Arecoline, the principal neuroactive alkaloid in areca nuts, was found in the mother's placenta.

Resting and arecoline‐stimulated brain metabolism and signaling involving arachidonic acid are altered in the cyclooxygenase‐2 knockout mouse

Abstract: Studies were performed to determine if cyclooxygenase (COX)-2 regulates muscarinic receptor-initiated signaling involving brain phospholipase A2 (PLA2) activation and arachidonic acid (AA; 20 : 4n-6) release. AA incorporation coefficients, k* (brain [1-14C]AA radioactivity/integrated plasma radioactivity), representing this signaling, were measured following the intravenous injection of [1-14C]AA using quantitative autoradiography, in each of 81 brain regions in unanesthetized COX-2 knockout (COX-2(-/-)) and wild-type (COX-2(+/+)) mice. Mice were administered arecoline (30 mg/kg i.p.), a non-specific muscarinic receptor agonist, or saline i.p. (baseline control). At baseline, COX-2(-/-) compared with COX-2(+/+) mice had widespread and significant elevations of k*. Arecoline increased k* significantly in COX-2(+/+) mice compared with saline controls in 72 of 81 brain regions, but had no significant effect on k* in any region in COX-2(-/-) mice. These findings, when related to net incorporation rates of AA from brain into plasma, demonstrate enhanced baseline brain metabolic loss of AA in COX-2(-/-) compared with COX-2(+/+) mice, and an absence of a normal k* response to muscarinic receptor activation. This response likely reflects selective COX-2-mediated conversion of PLA2-released AA to prostanoids.

Arecoline inhibits catecholamine release from perfused rat adrenal gland.

Abstract: To study the effect of arecoline, an alkaloid isolated from Areca catechu, on the secretion of catecholamines (CA) evoked by cholinergic agonists and the membrane depolarizer from isolated perfused rat adrenal gland. Adrenal glands were isolated from male Sprague-Dawley rats. The adrenal glands were perfused with Krebs bicarbonate solution by means of a peristaltic pump. The CA content of the perfusate was measured directly using the fluorometric method. Arecoline (0.1–1.0 mmol/L) perfused into an adrenal vein for 60 min produced dose- and time-dependent inhibition in CA secretory responses evoked by acetylcholine (ACh) (5.32 mmol/L), 1.1-dimethyl-4-phenyl piperazinium iodide (DMPP) (100 μmol/L for 2 min) and 3-(m-choloro-phenyl-carbamoyl-oxy)-2-butynyl trimethyl ammonium chloride (McN-A-343) (100 μmol/L for 2 min). However, lower doses of arecoline did not affect CA secretion of high K+ (56 mmol/L); higher doses greatly reduced CA secretion of high K+. Arecoline also failed to affect basal catecholamine output. Furthermore, in adrenal glands loaded with arecoline (0.3 mmol/L), CA secretory response evoked by Bay-K-8644 (10 μmol/L), an activator of L-type Ca2+ channels, was markedly inhibited, whereas CA secretion by cyclopiazonic acid (10 μmol/L), an inhibitor of cytoplasmic Ca2+-ATPase, was not affected. Nicotine (30 μmol/L), which was perfused into the adrenal gland for 60 min, however, initially enhanced ACh-evoked CA secretory responses. As time elapsed, these responses became more inhibited, whereas the initially enhanced high K+-evoked CA release diminished. CA secretion evoked by DMPP and McN-A-343 was significantly depressed in the presence of nicotine. Arecoline dose-dependently inhibits CA secretion from isolated perfused rat adrenal gland evoked by activation of cholinergic receptors. At lower doses arecoline does not inhibit CA secretion through membrane depolarization, but at larger doses it does. This inhibitory effect of arecoline may be mediated by blocking the calcium influx into the rat adrenal medullary chromaffin cells without the inhibition of Ca2+ release from the cytoplasmic calcium store. There seems to be a difference in the mode of action of nicotine and arecoline in rat adrenomedullary CA secretion.

Oral Submucous Fibrosis a Distressing Disease with Malignant Potential

Abstract: In their review, Pillai et al1 concluded that the etiology is unknown but is probably multifactorial Main contributing factor as thought by Jayanthi et al2, is the use of pan which typically consists of areca nut, tobacco and crude lime wrapped in betel leaf Experimentally, an alkaloid component of the areca nut, “Arecoline” can induce fi broblast proliferation and collagen synthesis and may penetrate the oral mucosa to cause progressive cross linking of collagen Fibres 3,4 Tobacco chewing and smoking are not considered to play a role in the development of this disease In this study we tried to analyze various clinico pathological aspect of the oral submucous fi brosis including the natural course of the disease

In vitro effects of arecoline on sperm motility and cyclooxygenase-2 expression.

Abstract: Semen samples were obtained from 30 volunteers who had never consumed betel quid. Swim-up spermatozoa from the 30 seminal samples of non-betel quid chewers and also non-smokers, usually not exposed to passive smoking, were treated in vitro with arecoline at different concentrations to evaluate the action of these drugs on sperm motility. Highly motile sperms were collected and divided into 5 equal fractions. Four fractions were supplemented with various concentrations of arecoline and one as control. The study was carried out at time 0 and +1, +2, +3 and +4 hr of incubation. Sperm cells were also extracted and blotted with COX-2 antibody after arecoline treatment after 4 hr incubation. The sperm motility parameters, i.e., motility, average path velocity, curvilinear velocity, straight-line velocity and linearity, were significantly decreased after arecoline treatment. In vitro, arecoline induces the COX-2 expression of sperm cells in a dose-dependent manner. This is the first report to demonstrate that arecoline may mediate COX-2 expression in human sperms, resulting in inflammation response. This situation may act on the structure responsible for the flagellar motion and cause the reduction of sperm motility.

Regulation effect of arecoline on excess expression of adhesive molecules in endothelial cells injuried with high concentration of D-glucose

Abstract: AIM: To investigate the effects of D-glucose on monocyte chemoattractant protein-1(MCP-1),intercellular cell adhesive molecule type-1(ICAM-1),vascular cell adhesive molecule1-1(VCAM-1)mRNA expression and the protective effects of arecoline,PPVP,DMHPPP and simvastatin in cultured bovine aorta endothelial cells,thereby to explore possible mechanisms by which the compounds prevent the formation of diabetic vascular complications.METHODS: Bovine aorta endothelial cells were cultured in vitro with indicated concentration of D-glucose for indicated time.After the cells were harvested at the specified situation,the MCP-1,ICAM-1 and VCAM-1 mRNA expression was detected by reverse transcription-polymerase chain reaction(RT-PCR) and normalized to the mRNA level of β-microglobulin in the absence or in the presence of D-glucose or land arecoline,PPVP,DMHPPP and simvastatin,respectively.RESULTS: The expression of MCP-1,ICAM-1 and VCAM-1 mRNA all increased dose-and time-dependently after treatments with 10,25,50(mmol·L~(-1)) D-glucose for 16 h and 25(mmol·L~(-1)) D-glucose for 8,16,24 h,respectively.Compare with control group,after the bovine aorta endothelial cells were incubated with 10-5(mmol·L~(-1)) arecoline,PPVP,DMHPPP,simvastatin for 20h in advance,respectively,the injury effects which were subsequently induced by 25(mmol·L~(-1)) D-glucose for 16h could be prevented.CONCLUSION: Cultured bovine aorta endothelial cells can express MCP-1,ICAM-1,and VCAM-1 mRNA at a low level,and high concentration of D-glucose can induce excess expression.The regulation effects of arecoline,PPVP,DMHPPP and simvastatin on the excess expressions are different,respectively.

Review on the actuality and prospect of areca alkaloids

Abstract: Alkaloids especially arecoline is the major pharmacologically active composition in areca nut. This paper reviews the extraction, isolation, identification, quantification, the positive and negative physiological effects of areca alkaloids. Meanwhile, the remaining problems of current investigation are discussed and the application of areca-alkaloids is prospected, leading people to study more about the deeping exploitation and full use of areca nut.

Protective effect of compounds on endothelial cells injuried with homocysteine

Abstract: Aim To investigate the effects of homocysteine on monocyte chemoattractant protein-1(MCP-1),intercellular cell adhesive molecule type-1(ICAM-1),vascular cell adhesive molecule1-1(VCAM-1)mRNA expression and the protective effects of arecoline,PPVP,DMHPPP and simvastatin in cultured bovine aorta endothelial cells,thereby to explore possible mechanisms by which the compounds affect the formation of atherosclerosis(AS).Methods Bovine aorta endothelial cells were cultured in vitro with indicated concentration of HCY for indicated time.After the cells were harvested at the specified situation,the MCP-1,ICAM-1 and VCAM-1 mRNA expression was detected by reverse transcription-polymerase chain reaction(RT-PCR) and normalized to the mRNA level of β-microglobulin in the absence or in the presence of homocysteine or land arecoline,PPVP,DMHPPP and simvastatin,respectively.Results The expression of MCP-1,ICAM-1 and VCAM-1 mRNA all increased dose-and time-dependently after treatments with 0.1,0.5,5.0 mmol·L~(-1) HCY for 6 h and 0.1 mmol·L~(-1) HCY for 3,6,12,24 h,respectively.Compared with control group,after the bovine aorta endothelial cells were incubated with 10 μmol·L~(-1) arecoline,PPVP,DMHPPP,simvastatin for 20 h in advance,respectively,the injury effects which were subsequently induced by 0.1 mmol·L~(-1) HCY for 6 h could be prevented.Conclusions Cultured bovine aorta endothelial cells could express MCP-1,ICAM-1,VCAM-1 mRNA at a low level,and HCY could induce a higher expression.The over expression could be blocked by arecoline,PPVP,DMHPPP and simvastatin.