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PubMed1990

A case-control study of oral submucous fibrosis with special reference to the etiologic role of areca nut.

A case-control study to elucidate the etiology of oral submucous fibrosis was conducted in Bhavnagar, Gujarat. Sixty consecutively arriving oral submucous fibrosis patients at a dental clinic were selected as cases. An equal number of controls matched for age, sex, religion and socioeconomic status were selected from individuals who did not exhibit any oral mucosal lesion or condition. Among cases, 98% chewed areca nut regularly in one form or the other whereas among controls 35% chewed areca nut, giving an overall relative risk of 109.6. Areca nut chewing was practiced most commonly in the form of mawa: a mixture containing mainly areca nut (over 90% by weight), some tobacco, and a few drops of lime. Mawa chewers and those who chewed mawa along with other chewing habits showed very high relative risks. The relative risks increased with increase in the frequency as well as the duration of chewing habits. In a bivariate analysis the effect of frequency and duration of chewing appeared to be multiplicative. The present findings confirm areca nut as the most important etiologic factor in oral submucous fibrosis.

Adolescent↗
PubMed2006

Enhancing effects of areca nut extracts on the production of interleukin-6 and interleukin-8 by peripheral blood mononuclear cells.

BACKGROUND: The habit of chewing areca quid (AQ) has been implicated in oral pathogenesis, including periodontal disease. Little is understood about the roles of AQ in the cytokine secretion by immune cells. The study examined the effects of areca nut, the major ingredient of AQ, on the production of interleukin (IL)-6 and IL-8 by peripheral blood mononuclear cells (PBMC), the immunocompetent cells. The possible role of oxidative stress of areca nut was also examined. METHODS: Extracts of ripe areca nut (rANE) and tender areca nut (tANE) were examined for their cytotoxic effects on human PBMC using the trypan blue exclusion test. The production of IL-6 and IL-8 by ANE-treated PBMC was analyzed using enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction. Effects of an antioxidant, pyrrolidine dithiocarbamate (PDTC), on ANE-induced cytokine secretion were also studied. RESULTS: At the experimental conditions, 20 micro g/ml rANE decreased cell viability significantly, whereas no significant effect of tANE (< or =80 micro g/ml) was observed. Both rANE (< or =20 micro g/ml) and tANE (< or =160 micro g/ml) significantly increased the secretion of IL-6 and IL-8 by PBMC in a dose- and time-dependent manner. The altered mRNA expression of IL-6 by rANE and tANE was also observed. Moreover, the stimulating effects of rANE on cytokine expression in PBMC could be attenuated by PDTC, suggesting that the oxidative stress of rANE may play a role. CONCLUSIONS: Markedly enhancing effects of ANE on PBMC-released inflammatory cytokines might cause a sustained cytokine-rich inflammatory milieu in oral cavity of AQ chewers. These excessive cytokines from ANE-treated immune cells may impair periodontal health.

Areca↗
PubMed2002

Effect of areca on contraction of colonic muscle strips in rats.

AIM: To investigate the effects of areca on the contractile activity of isolated colonic muscle strips in rats and mechanism involved. METHODS: Each strip (LMPC, longitudinal muscle of proximal colon; CMPC, circular muscle of proximal colon; LMDC, longitudinal muscle of distal colon; CMDC, circular muscle of distal colon.) was suspended in a tissue chamber containing 5 mL Krebs solution (37 degrees C), bubbled continuously with 950 mL.L(-1) O(2) and 50 mL.L(-1) CO(2). The mean contractile amplitude (A), the resting tension (T), and the contractile frequency (F) were simultaneously recorded on recorders. RESULTS: Areca dose dependently increased the mean contractile amplitude, the resting tension of proximal and distal colonic smooth muscle strips in rats (P<0.05). It also partly increased the contractile frequency of colonic smooth muscle strips in rats (P<0.05). The effects were partly inhibited by atropine (the resting tension of LMPC decreased from 0.44 +/- 0.12 to 0.17 +/- 0.03; the resting tension of LMDC decreased from 0.71 +/- 0.14 to 0.03 +/- 0.01; the mean contractile amplitude of LMPC increased from -45.8 +/- 7.2 to -30.5 +/- 2.9; the motility index of CMDC decreased from 86.6 +/- 17.3 to 32.8 +/- 9.3; P<0.05 vs areca), but the effects were not inhibited by hexamethonium (P>0.05). CONCLUSION: Areca stimulated the motility of isolated colonic smooth muscle strips in rats. The stimulation of areca might be relevant with M receptor partly.

Animals↗
PubMed1989

Cytotoxic and genotoxic effects of areca nut-related compounds in cultured human buccal epithelial cells.

Because betel quid chewing has been linked to the development of oral cancer, pathobiological effects of an aqueous areca nut extract, four areca nut alkaloids (arecoline, guvacoline, guvacine, and arecaidine), and four nitrosated derivatives [N-nitrosoguvacoline, N-nitrosoguvacine, 3-(N-nitrosomethylamino)propionaldehyde and 3-(N-nitrosomethylamino)propionitrile] have been investigated using cultured human buccal epithelial cells. Areca nut extract in a dose-dependent manner decreases cell survival, vital dye accumulation, and membrane integrity, and it causes formation of both DNA single strand breaks and DNA protein cross-links. Depletion of cellular free low-molecular-weight thiols also occurs, albeit at quite toxic concentrations. Comparisons of the areca nut-related N-nitroso compounds and their precursor alkaloids, at concentrations up to 5 mM, indicate that 3-(N-nitrosomethylamino)propionaldehyde is the most potent on a molar basis to decrease both survival and thiol content and to cause significant formation of DNA single strand breaks. Arecoline, guvacoline, or N-nitrosoguvacoline decreases survival and cellular thiols, whereas arecaidine, guvacine, N-nitrosoguvacine, and 3-(N-nitrosomethylamino)propionitrile have only minor effects on these variables. Taken together, the present studies indicate that aqueous extract and, in particular, one N-nitroso compound related to areca nut, i.e., 3-(N-nitrosomethylamino)propionaldehyde, are highly cytotoxic and genotoxic to cultured human buccal epithelial cells, of potential importance in the induction of tumors in betel quid chewers.

Arecoline↗
PubMed2005

Areca (betel) nut extract activates mitogen-activated protein kinases and NF-kappaB in oral keratinocytes.

Areca (betel) was recently proved a carcinogenic substance by the International Agency for Research on Cancer. However, the signaling impact of areca in oral keratinocyte is still obscure. Mitogen-activated protein kinase superfamilies, including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinases (JNK) and p38, together with transcription factor NF-kappaB, are important signaling elements. We examined the activation of these signaling pathways in OECM-1 and SAS oral keratinocytes, treated with ripe areca nut extract (ANE). In both cells, a rapid increase in JNK1 activity at 0.5 hr was noted following treatment of ANE. ERK was profoundly activated during 0.5-2 hr in OECM-1 cells. Contrasting p38 activity was noted in these 2 cells. In both cells, ANE also activated NF-kappaB pathway in a biphasic manner, particularly for SAS cells. NF-kappaB was activated by approximately 2- to 4-fold at 0.5-1 hr and a plateau or slight decrease of activity existed between 1 and 6 hr. Later, another higher episode of NF-kappaB activity was raised. This was accompanied with the rapid degradation in cytosolic IkappaBalpha as well as an increase of nuclear NF-kappaB in both cells. ANE treatment did not activate epidermal growth factor receptor signaling system, but blockage of NF-kappaB activation rendered the suppression of ANE-modulated COX-2 upregulation in OECM-1. This study identified that ANE affected interactive signaling systems in oral keratonocytes that could be the pathogenetic basis for areca.

Areca↗
PubMed1992

In vitro genotoxic effects of areca nut extract and arecoline.

The genotoxic potential of the aqueous extract of areca nut as well as arecoline, the major alkaloid of the areca nut, was tested with the help of cytogenetic markers such as sister-chromatid exchanges and chromosome aberrations, utilizing Chinese hamster ovary (CHO) cells. The continuous-treatment and pulse-treatment schedules yielded dose-dependent elevations in the frequencies of sister-chromatid exchange and chromosomal aberration in CHO cells, indicating a genotoxic effect of both the extract and arecoline. The results also imply that, besides arecoline, there may be some other water-extractable substances in the areca nut that make the extract more genotoxic. The chromosome damage was found to be more severe on treating the cells with low concentrations and for longer duration, which mimic the effects of chronic areca nut consumption.

Animals↗
PubMed2001

Role of areca nut in betel quid-associated chemical carcinogenesis: current awareness and future perspectives.

Betel quid (BQ)-chewing is a popular oral habit with potential links to the occurrence of oral cancer. Many of the literature-based studies reveal that areca nut (AN) extract may demonstrate mutagenic and genotoxic effects, in addition to inducing preneoplastic as well as neoplastic lesions in experimental animals. Areca nut should, thus, be highly suspected as a human carcinogen. Toxicity studies relating to AN-contained polyphenols and tannins are not conclusive, with both carcinogenic and anti-carcinogenic effects being reported. The mutagenicity and genotoxicity of areca alkaloids has been detected by many short-term assays. However, their genotoxicity to oral fibroblasts and keratinocytes, the target cells of BQ, has not been identified. It would thus appear that AN toxicity is not completely due to its polyphenol, tannin and alkaloid content. The single agent which is responsible for AN carcinogenicity awaits further clarification. Reactive oxygen species produced during auto-oxidation of AN polyphenols in the BQ-chewer's saliva, are crucial in the initiation and promotion of oral cancer. Nitrosation of areca alkaloids also produces AN-specific nitrosamines, that have been demonstrated to be mutagenic, genotoxic and are capable of inducing tumors in experimental animals. Arecaidine and AN extract are further suggested to be tumor promoters. Antioxidants such as glutathione and N-acetyl-L-cysteine can potentially prevent such AN-elicited cytotoxicity. Further studies are needed to delineate the metabolism of AN ingredient and their roles in the multi-step chemical carcinogenesis, in order to enhance the success of the future chemoprevention of oral cancer and oral submucous fibrosis.

Alkaloids↗
PubMed2004

Polymorphism in heme oxygenase-1 (HO-1) promoter is related to the risk of oral squamous cell carcinoma occurring on male areca chewers.

Areca (betel) chewing is associated with the high incidence of oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSF) in Asians. Heme oxygenase-1 (HO-1), encoding an oxidative response protein, plays protective roles in cells. A (GT)n microsatellite repeat in HO-1 promoter shows polymorphisms and modulates the level of gene transcription. We examined allelotypic frequencies of (GT)n repeats in 83 controls, 147 OSCC and 71 OSF. All subjects were male areca chewers. Logistic regression was used to adjust the age confounding for odds ratio (OR). (GT)n repeat polymorphism was classified into short (S), medium (M) and long (L) alleles. The adjusted OR in OSCC subjects carrying L allelotype relative to S allelotype was 1.75. Buccal squamous cell carcinoma (BSCC) is the most common OSCC subset in areca chewers. L allelotype implied the risk of BSCC with adjusted OR of 2.05, whereas M allelotype appeared protective for non-BSCC with adjusted OR of 0.49. Our findings indicated that longer (GT)n repeat allele in HO-1 promoter is associated with the risks of areca-related OSCC, while the shorter (GT)n repeat allele may have protective effects for OSCC.

Areca↗
PubMed2002

Anthropological perspectives on use of the areca nut.

This paper first reviews the identity of historical and contemporary users of the areca nut. It then considers the reasons given by users for indulging in areca consumption, drawing upon historical, ethnographic and experimental sources of evidence for the effects which users have sought to derive from it. Particularly important is the social context in which consumption occurs, and the social meanings attached to areca use and exchange. Finally, a possible evolutionary hypothesis is postulated to explain the origins of areca use as a form of behaviour indicating reproductive availability. However, diverse culturally explicit reasons underlie usage and what may once have been a sufficient rationale for consumption may no longer justify this pattern of behaviour.

Anthropology, Cultural↗
PubMed2005

Areca nut extracts modulated expression of alkaline phosphatase and receptor activator of nuclear factor kappaB ligand in osteoblasts.

OBJECTIVES: Areca chewers have a higher prevalence of periodontal diseases than non-chewers. This study was to determine the possible effects of ripe areca nut extracts (rANE) on viability and gene expression of alkaline phosphatase (ALP), receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) in human osteoblasts. METHODS: The effects of rANE on cell viability of osteoblast-like MG63 cells were determined using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) that measures metabolic activity. Gene expression of ALP, RANKL and OPG was examined using reverse transcription-polymerase chain reaction. ALP activity and RANKL protein were further examined using substrate assay and confocal laser scanning microscopy, respectively. RESULTS: Relative viability was reduced to approximately 50% when 25 microg/ml of rANE was used. The expression of OPG mRNA in MG63 cells was not altered by rANE. However, decreased levels of mRNA and enzyme activity of ALP were observed. Moreover, the expressions of mRNA and protein of RANKL were stimulated by rANE in a dose-dependent manner. CONCLUSIONS: The rANE affected morphology and viability of osteoblasts. We also present novel evidence demonstrating that areca nut may compromise the periodontal health of areca chewers by suppression of ALP gene expression and elevation of RANKL gene expression in osteoblasts.

Alkaline Phosphatase↗
PubMed1999

Oral mucosal lesions associated with betel quid, areca nut and tobacco chewing habits: consensus from a workshop held in Kuala Lumpur, Malaysia, November 25-27, 1996.

A variety of betel/areca nut/tobacco habits have been reviewed and categorized because of their possible causal association with oral cancer and various oral precancerous lesions and conditions, and on account of their widespread occurrence in different parts of the world. At a recent workshop in Kuala Lumpur it was recommended that "quid" be defined as "a substance, or mixture of substances, placed in the mouth or chewed and remaining in contact with the mucosa, usually containing one or both of the two basic ingredients, tobacco and/or areca nut, in raw or any manufactured or processed form." Clear delineations on contents of the quid (areca nut quid, tobacco quid, and tobacco and areca nut quid) are recommended as absolute criteria with finer subdivisions to be added if necessary. The betel quid refers to any quid wrapped in betel leaf and is therefore a specific variety of quid. The workshop proposed that quid-related lesions should be categorized conceptually into two categories: first, those that are diffusely outlined and second, those localized at the site where a quid is regularly placed. Additional or expanded criteria and guidelines were proposed to define, describe or identify lesions such as chewer's mucosa, areca nut chewer's lesion, oral submucous fibrosis and other quid-related lesions. A new clinical entity, betel-quid lichenoid lesion, was also proposed to describe an oral lichen planus-like lesion associated with the betel quid habit.

Areca↗
PubMed2004

Establishment of OC3 oral carcinoma cell line and identification of NF-kappa B activation responses to areca nut extract.

BACKGROUND: Cell lines derived from oral squamous cell carcinoma (OSCC) exposed to variable etiological factors can bestow advantages in understanding the molecular and cellular alterations pertaining to environmental impacts. Most OSCC cell lines have been established from smoker patients or areca chewing/smoker patients, carrying the genomic alterations in p53. METHODS: A new cell line, oral carcinoma 3 (OC3), was established from an OSCC in a long-term areca (betel) chewer who does not smoke. Cellular and molecular features of OC3 were determined by variable assays. RESULTS: The cultured monolayer cells were mainly polygonal and had the expression of cytokeratin 14. The chromosomal analysis using comparative genomic hybridization has revealed the gain in chromosomes 1q, 5q, and 8q, the loss in 4q, 6p, and 8p as well as the gain of entire chromosome 20. Loss of heterozygosity and instability in multiple microsatellite markers in chromosome 4q were also noted. OC3 cells bear wild-type p53 coding sequence and have a high level of p53 expression. Its p21 expression was similar to that in normal human oral keratinocyte (NHOK). Interestingly, activation of nuclear factor kappa B (NF-kappa B) in OC3 cells following the treatment of areca nut extract was observed. CONCLUSION: OC3 cell line could be valuable in understanding the genetic impairments and phenotypic changes associated with areca in oral keratinocyte.

Areca↗
PubMed2005

Oral precancerous disorders associated with areca quid chewing, smoking, and alcohol drinking in southern Taiwan.

OBJECTIVE: To investigate the prevalence and the associated risk factors of oral precancerous disorders in southern Taiwan. METHODS: We conducted a cross-sectional community survey interviewing 1075 adult subjects, 15 years of age and over, gathered from randomly selected 591 households, and spanning five villages in southern Taiwan. The study protocol included a visual oral soft tissue examination and a questionnaire-based interview. The chi-square test was used to test the differences in prevalence of oral precancerous lesions and conditions by different "life styles" relating to current risk habits of current areca quid chewing, smoking, and alcohol drinking. To control for possible confounding, a logistic regression model was used to estimate the Odds Ratios (OR) for leukoplakia and oral submucous fibrosis (OSF). RESULTS: 136 precancerous lesions and conditions were detected among 1075 subjects (12.7%). The analysis of the spectrum of oral precancerous disorders detected, leukoplakia (n = 80), OSF (n = 17) and verrucous lesions (n = 9), demonstrated an association with gender (P < 0.001). There were statistically significant associations among leukoplakia (P < 0.01), OSF (P < 0.0001), and verrucous lesions (P < 0.0001) and the life style of current areca quid chewing, smoking, and alcohol drinking. The synergistic effect of smoking and areca quid chewing habit on leukoplakia and OSF was demonstrated. CONCLUSION: This study reinforces the association of current areca quid chewing without tobacco, cigarette smoking, and alcohol drinking to leukoplakia, OSF, and verrucous lesions in Taiwan.

Adolescent↗
PubMed2000

Effect of betel/areca nut (Areca catechu) extracts on intestinal epithelial cell lining.

Carcinogenic and other toxic manifestations of areca/betel nut extracts on the buccal cavity and upper digestive tract are well documented. The present study deals with in vivo and in situ effects of aqueous and alcoholic extracts of areca nut on rat intestinal epithelial cell membrane. In vivo daily oral administration by gastric intubation for 1p w produced significant declines in brush border membrane alkaline phosphatase, Ca2+-Mg2+-ATPase, and the digestive enzyme sucrase. The decline in activities were more prominent after 4-w exposures. Instant short term in situ exposure to aqueous extract produced higher enzyme activities, indicating the initial activation of active sites by areca nut extract constituent(s). Significant declines in brush border membrane constituents (total hexose, sialic acid and cholesterol) were also evident following continuous exposures to areca nut extracts. These findings suggest that prolonged chewing of areca nut causes significant alterations in intestinal epithelial cell lining functions and could lead to malabsorption of nutrients.

Administration, Oral↗
PubMed1992

[A thin layer chromatography densitometric method for the determination of arecoline content in semen Arecae from different producing areas].

A TLC-densitometric method for the determination of arecoline in Semen Arecae (Areca catechu) was established, and arecoline content in three Semen Arecae (Imported, Hainan, Guanzhou) was determined. The method is accurate, sensitive and simple. The recovery is 102.39% and the coefficient of variation of six samplings is 1.95%. The are coline average content in the three Semen Arecae is 0.22%, 0.19%, 0.56% respectively.

Areca↗
PubMed2006

Areca nut use amongst South Asian schoolchildren in Tower Hamlets, London: the extent to which the habit is engaged in within the family and used to suppress hunger.

OBJECTIVES: To examine the extent to which an areca nut habit is engaged in within the family and degree to which the habit may be used to suppress hunger amongst South Asian schoolchildren with a view to informing health promotion campaigns. RESEARCH DESIGN: Self-administered questionnaire. SETTING: Two comprehensive schools (one mixed, one all girls) in the Tower Hamlets district of East London, UK. PARTICIPANTS: 341 (285 girls; 56 boys) children of self-reported South Asian origin (Bangladeshi 286, Pakistani 4, Asian, 51) who reported currently engaging in an areca nut habit. RESULTS: Areca nut habits were mainly used in a family context. Smaller proportions of children reported predominant use alone or with peers. A substantial minority reported using their habit to suppress hunger. CONCLUSION: The family plays a crucial role in maintaining areca nut use. This implies effective health promotion campaigns must operate at the family and even community levels rather than being targeted at the children directly.

Adolescent↗
PubMedDate not supplied

Chewing of betel, areca and tobacco: perceptions and knowledge regarding their role in head and neck cancers in an urban squatter settlement in Pakistan.

The link of betel, areca and chewable tobacco with head and neck cancers is clearly established. Fifty eight percent of the global head and neck cancers occur in South and Southeast Asia, where chewing of betel, areca and tobacco are common. This study was carried out to establish the pattern of use of Paan, Chaalia, Gutka, Niswar, Tumbaku and Naas among population of squatter settlement of Karachi and to determine the perceptions and knowledge regarding their role in the etiology of head and neck cancers. It was a cross-sectional study, performed at Bilal colony in Karachi. Through systematic sampling, 425 subjects [a male and female from a household] were interviewed with a structured questionnaire. Knowledge regarding etiology of head and neck cancers was classified in ordinals of "good", "some" and "poor", for each substance separately, while practices were classified into "daily user", "occasional user" and "never user". About 40% of the participants were chewing at least one item [betel, areca or tobacco products] on daily basis. This prevalence was 2.46 times higher among males than females and 1.39 times higher among adolescents than adults. At least 79% of the participants were classified as having poor knowledge about the carcinogenicity of each of these items. Knowledge increased with age and level of education. Health hazards of these items were poorly recognized and about 20% perceived at least one of these items to be beneficial. Positive attitudes were seen regarding the steps to curb the production, business and consumption of these substances. In conclusion, prevalence of chewing of betel, areca and tobacco among adults and adolescents is high. Deficiency in knowledge and wrong perception of favorable effect of chewing products is common. Besides curtailing the availability of chewing products, correct knowledge regarding its ill-effects should be inculcated among population to decrease the burden of head and neck cancers.

Adolescent↗
PubMed1989

Evaluation of the carcinogenicity of different preparations of areca nut in mice.

Areca nut has been used as a masticatory since antiquity and it is estimated that more than 10% of the world population chews it in a variety of forms. We have evaluated the carcinogenicity of different preparations of areca nut: ripe-unprocessed-sundried nut (R-UP-SD), ripe-processed-sundried nut (R-P-SD), unripe-processed-sundried nut (UR-P-SD), ripe-unprocessed-sundried-water-soaked nut (R-UP-SD-WS) and ripe-unprocessed-undried-water-soaked nut (R-UP-UD-WS) in mice following diet-feeding or oral feeding for 12 months. Only unprocessed areca nuts (R-UP-SD, R-UP-SD-WS and R-UP-UD-WS), at high doses, displayed a very weak carcinogenicity.

Administration, Oral↗