|Year : 2019 | Volume
| Issue : 2 | Page : 31-38
Genotoxic burden of water pipe smoking in arabian countries: The risk in female population
Dhafer Mahdi Alshayban1, Faheem Hyder Pottoo2, Muhammad Tariq Aftab3
1 Department of Clinical Pharmacy, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University(Formerly University of Dammam), Dammam, Saudi Arabia
2 Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University (Formerly University of Dammam), Dammam, Saudi Arabia
3 Department of Pharmacology and Therapeutics, College of Medicine, Islam Medical and Dental College, Sialkot, Pakistan
|Date of Submission||31-Mar-2019|
|Date of Acceptance||30-May-2019|
|Date of Web Publication||30-Jul-2019|
Dr. Faheem Hyder Pottoo
Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University (Formerly University of Dammam), 1982 Dammam
Source of Support: None, Conflict of Interest: None
The perception that water pipe smoking (WPS) is safe mode of smoking is biased; the purpose of this study was to review literature for genotoxic effects of WPS and associated vital organ damage. The amount of nicotine, polycyclic aromatic hydrocarbons, carbon monoxide, tar, and heavy metals delineated after prolonged exposure to WPS exceeds that reported for cigarette smoking (CS). WPS is related to diverse adverse health consequences on cardiovascular, respiratory, hematological, and reproductive systems without sparing infants who are reported to born with reduced birth weight and length from exposed mothers. WPS causes significant reduction in mRNA expression levels of DNA repair genes (OGG1 and XRCC1) compared to CS and predisposes to heightened risk of developing bladder cancer, lung cancer, prostate cancer, and pancreatic cancers. Education about the harmfulness of WPS and policies to limit its use should be implemented, particularly in females (Graphical Abstract).
Keywords: Carcinoma, cigarette smoking, genotoxicity, nicotine, tar, water pipe smoking
|How to cite this article:|
Alshayban DM, Pottoo FH, Aftab MT. Genotoxic burden of water pipe smoking in arabian countries: The risk in female population. Imam J Appl Sci 2019;4:31-8
|How to cite this URL:|
Alshayban DM, Pottoo FH, Aftab MT. Genotoxic burden of water pipe smoking in arabian countries: The risk in female population. Imam J Appl Sci [serial online] 2019 [cited 2020 Aug 5];4:31-8. Available from: http://www.e-ijas.org/text.asp?2019/4/2/31/263665
| Introduction|| |
Water pipe smoking (WPS) also named Shisha, Hookah, Narghile, Arghile, Ghoza, Borry, Shui Yan Dai, and Hubble Bubble sprouted in India, South Africa, Persia, and Ethiopia and presently is a practice in Arab countries, involving ostentatious youth., It is a traditional and at the same time modern method of smoking tobacco in most Arabian countries. WPS inculpates burning of charcoal, with or without ma'assel (a flavored tobacco-based mixture). Water pipe smoke contains gases and particles emerging from the charcoal and blazing tobacco. It has been estimated that a single water pipe session extends 60 min (approximately) and involves 200 puffs (i.e., 90,000 ml of smoke is inhaled/session) in contrast to a single cigarette session (5 min) with approximately 500–600 ml of smoke inhaled (i.e., 10–13 puffs of about 50 ml). It has become a global epidemic with >100 million people worldwide smoking water pipes each day. The WPS is simply reshaping smoking, causing 11.5% of deaths worldwide and is a major preventable enigma in most countries. WPS causes more hospitalizations than combined abuse of alcohol and illicit drugs in some countries. Although its rates have fallen in many resource-rich countries due to policy changes such as escalation in tobacco taxes, restrictions on advertising, promotion and sponsorship of tobacco products, mass media campaigns, and pictorial health-warning labels,, but overall decline has not been uniform, plotted by pioneering of Maassel (flavored tobacco), flourishing café culture, advertising, and deficit state regulatory policies. Its count remains higher among the poor, less educated, and in the nations with less access to prevention or treatment.
Nicotiana tabacum is the source of the tobacco which is commonly used in WPS. N. tabacum has been subject of exhaustive research due to pleasure and addictive properties inculcated in its compounds. The alkaloids (nitrogen-containing secondary metabolites) reported from N. tabacum are nicotine (90%), anabasine, cytisine, n-methylcytisine, coniine, n-methylconiine, and gamma-coniceine., These alkaloids are agonists at nicotinic-acetylcholine receptors (nAChRs). Acute exposure to nicotine presents with early symptoms of abdominal pain, hypertension, tachycardia, and tremors while later, hypotension, bradycardia, dyspnea, coma, and respiratory failure follows. Apart from alkaloids, the carcinogenic substances reported are N-nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), numerous polycyclic aromatic hydrocarbons (PAHs) (e.g., benzo[a] pyrene), radioactive polonium, and benzene.
Dependence on tobacco has been primarily attributed to the ability of nicotine to stimulate the reward circuit in the brain, which is similar to the biological mechanism of dependency for abuse with other substances. The possibility of genetic influences on this mechanism has been considered in the context of candidate genes in the dopaminergic reward system pathway. Multiple allelic forms are recognized for dopamine (D2) receptor gene which is positioned on chromosome 11 (q22-23). A restriction fragment length polymorphism (TaqI) has been described in the 3′ untranslated region, localized to the adjacent ANKK1 gene with alleles deputed as dopamine receptor gene (DRD2*A1 and *A2). The A1 allele has been linked with lower brain sites for dopamine binding. Consequently, Radwan et al., 2010 reported 34.4% prevalence of the A1 allele in WPS from rural Upper Egypt. The persons with A1 alleles unveil dearth in dopaminergic transmission and thereby consume nicotine to augment dopamine release in the brain. WPS is significantly associated with increased risk of mortality from cancer and ischemic heart disease. Similarly, CS increases the risk of death from diverse causes such as renal failure, hypertensive heart disease, intestinal ischemia, prostate cancer (in males), breast cancer (in females), liver cirrhosis, and infections). Adding to the irony, WPS leads to higher risks of abusing cigarettes.
Saudi Arabia is going to face WPS as a prime public health concern in near future which has been proved by growing epidemiological evidences. In fact, the trend of WPS is alarming and it is surpassing that for CS. Unfortunately, people inadvertently consider WPS as less injurious and less addictive (habit forming) than CS, which encourages continued use and disinterest in abandoning hookah in societies.,,,
| Water Pipe Smoking in Arabian Countries: Saudi Arabia|| |
Gender difference is significant in smoking as 1:4 men and 1:19 women, smoke tobacco each day according to systematic analysis of studies conducted in 195 countries and territories published in 2015. Although females are less involved, genotoxic threat in infants renders it of paramount significance. Since WPS is developed in group setting, the involvement of females actively or passively has been seen right from the start of this practice. The smoke from shisha comprises of fumes emerging from tobacco and charcoal, and contains CO, nitric oxide (NO), PAHs, volatile aldehydes, nicotine, furans, and nanoparticles.,,,,, In a survey at King Saud University, Riyadh, Saudi Arabia, the female students were reported as 5.6% water pipe (WP) smokers, 4.3% cigarette smokers (CSs), and 3.9% ex-smokers while 46% had started smoking at the high school or intermediate school level and remaining afterwards. The 77% were motivated by family member(s) and 19% by friends or the media. Al Moamary et al., 2012 reported 65.9% male and 34.1% female had tried WPS at a high school in Riyadh, KSA. The prevalence of smoking was lower in medical female students (0.32%) compared to nonmedical female students (4.2%) attending King Abdul-Aziz University, Jeddah. Koura et al., 2011 classified that in Dammam, 8.6% of female college students are smokers (science students 3.4% and literature students 12.1%), among which 56.80% smoked cigarette and 43.2% WP. The study from Jordan reported 7.9% of women as CS and 8.7% as WPS. The women were exposed to second hand cigarette and water pipe smoke at their houses (50.4% and 48.7%) and public places (31.4% and 21.4%), while husband remained the main source of exposure (48.5% and 42.7%). Unfortunately, only 55.1% Jordan women deemed that WPS is addictive, while 74% considered addiction with CS. Malaysian study claimed 20% prevalence of WPS among medical students, and with false perception that water in hooka “filters” toxins (67% female; 33% male).
Genotoxicity and cancer
Tobacco smoke is the most utmost symbol of a systemic human mutagen. Eighty-one compounds of cigarette mainstream smoke are IARC-classified carcinogens. It proves relatively high mutagenic potential of WPS. Hooka is associated with pathologic abnormalities alike chronic CS. The perception that narghile or shisha is safe mode of smoking is wrong; an appreciable segment of hookah smokers (43%) have outrageous and prohibitive levels of carcinoembryonic antigen (7.1 ± 10.48 ng/ml), the levels of which are elevated in both malignant and nonmalignant tumors. Knishkowy and Amitai, 2005 relayed predisposition to bladder cancer with WPS in Egyptian population with a prevalence of 15.3% in rural males and 10.9% in urban males. A Kashmir-based study reported that WPS is associated with six times more risk for lung cancer growth compared to nonsmokers, in ethnic kashmiri population. While other study from the same region reported WPS and nass chewing to escalate risk of esophageal squamous cell carcinoma by two- to three-fold. The laryngeal video-end stroboscopic evaluation of hooka smokers, revealed 21.5% incidence of benign lesions of the vocal folds (edema; 16.7% and cyst; 4.8%). Iranian study described WPS as a risk factor for prostate cancer. WPS is also reported to be paramount risk factor in the development of pancreatic cancers. The WPS induced DNA damage is analyzed by several tests including micronuclei (MN) assay, comet assay, DNA adducts, sister chromatid exchanges (SCEs), 8-hydroxyguanosine, and chromosomal aberrations (CAs). The micronucleus test is used to determine if a compound is genotoxic by evaluating the presence of MN. MN may contain chromosome fragments produced from DNA breakage (clastogens) or whole chromosomes produced by disruption of the mitotic apparatus (aneugens). The Comet assay spots recent lesions that can be repaired, such as breaks and alkali-labile sites. The MN test applied to the buccal epithelial cells from hookah smokers revealed 36% higher MN than nonsmokers. MN evaluation in the exfoliated oral cells of shisha smokers were two-fold higher than in nonsmokers. Micronucleus elevation was associated with the extent of shisha smoking per week (P = 0.021), alcohol consumption (P = 0.021), and BMI (P = 0.027). It seems that long-term consumption of shisha in both genders could increase the risk of genetic toxicity and occurrence of malignancies in human target cells. The comet assay on human peripheral blood leukocytes reported smoke condensate from jurak and moassel as genotoxic. Further WPS caused DNA mutilation in vivo in buccal cells of smokers. The tail moment and tail length in buccal cells of smokers were 186 ± 26 and 456 ± 71, respectively, which were elevated than control. Khabour et al., 2011 reported that WPS is associated with more inflation in SCEs than CS, unveiling that WPS is more genotoxic than CS. Walters et al., 2017 conducted genome-wide comparison of small airway epithelium DNA methylation in WPS compared to nonsmokers and concluded that 727 probesets are divergently methylated (fold change > 1.5, P < 0.05) portraying 673 unique genes. The predominant pathways related to these epigenetic changes invoke those associated with GPCR-signaling, aryl hydrocarbon receptor signaling, and xenobiotic metabolism signaling. A significant (P < 0.05) portion (11.3%) of methylated genes unveiled change in expression related to eIF2 signaling and regulation of eIF4 and p70S6K signaling. Korashy and Attafi, 2017 reported significant reduction in mRNA expression levels of DNA repair genes (OGG1 and XRCC1) in hooka (60%) and CSs (30%). Which was allied to prominent reduction (50%) in the expression of GST (detoxifying gene). The genotoxic potential of WPS is also confirmed from animal studies. The comet assay and MN test revealed that exposure of snails (H. aspersa) to tobacco leaves caused notable DNA damage, along with inhibition of cytochrome P450 enzymes. Nicotine was found to induce chromosome aberration (CA) and frequency of SCE in a dose- and duration-dependent manner in Chinese hamster ovary cells [Table 1].
Vulnerability to toxins
The exposure of smoker to smoke is more with WPS (longer smoking sessions) compared to CS. Al-Amrah et al., 2014 reported that WPS sessions end within 20–80 min, throughout which the smoker takes around 50–200 puffs. Incontast CS takes 8–12, 40–75 ml puffs over about 5–7 min. Consequently, the WPS inhales smoke an equivalent of 100 or more cigarettes during one session. Exorbitant, levels of carboxyhemoglobin (COHb), a reliable marker of CO in the blood was reported with WPS compared to CS.,, The laboratory comparison of the toxicant exposure associated with WPS and CS revealed that expired-air CO after session's end increased by 23.9 ppm for WPS (SD = 19.8) and 2.7 ppm for CS (SD = 1.8), while peak water pipe COHb blood levels for WPS (M = 3.9%, SD = 2.5) were three times those observed for CS (M = 1.3%, SD = 0.5; P < 0.001). This study utilized participants with WPS sessions of 5.2/month (each session for 45 min) and CS sessions of 9.9 cigarettes/day. Blank et al., 2011 confirms that WPS raises levels of COHb and nicotine in blood. COHb retards oxygen release to tissues. Water pipe smoke contains 802 mg of tar, 145 mg of CO compared to 22.3 mg and 17.3 mg for cigarettes, accordingly 36 times the tar and 8 times the CO is present in water pipe smoke compared to cigarette smoke. The WPS contains 36 times the amount of nicotine in cigarettes and a lofty quantum of heavy metals., These findings have been validated by Cobb et al., 2010 who reported that smoke from single session of WP (approximately 90,000 ml) contains 1.7 times the nicotine, 8.4 times the CO, and 36.0 times the tar compared to 500 ml of smoke produced from single session of cigarette. Urine shows presence of PAH metabolites and TSNAs. Another study showed that water pipe is just as dangerous for a person's health as cigarettes. The flaming temperature for WPS (900°C) is 2 times that for cigarettes (450°C), thus creates diverse types of baleful chemicals. Experiments have demonstrated dose-dependent effects of nicotine on DNA damage. It is also found to sensitize cells for the genotoxic substances.
WPS has been found to be associated with many cardiovascular pathologies in a number of Clinical studies., Higher serum NO levels were detected in shisha smokers (34.3 μmol/L) compared to the nonsmokers (22.5 μmol/L). Acute exposure to WPS escalates heart rate (HR) and blood pressure integrated with reduced baroreflex sensitivity, exercise capacity and HR variability. Chronic exposure is intricately linked to coronary artery disease and perhaps a higher degree of endothelial dysfunction., Elevation in high sensitivity C reactive protein and reduction in flow-mediated dilatation in WPS, which are best recounted as prognostic factors for cardiovascular disease are reported. These pathologies increase exposure of different organs to nicotine and its metabolites by increasing retention time and also enhance genotoxicity after passing into fetus. A significant association between WPS and myocardial infarction (MI) was reported in Lebanese patients referred for cardiac catheterization and was less so for CS. In addition, among MI enrollees diabetes group showed significant association with WPS. The animal studies confirm findings from clinical studies. Nemmar et al., 2013 reported that cardiomyocytes and noncardiomyocytes cells of mice exhibit escalation in the expression of inducible NO synthase (iNOS) on exposure to WPS, compared with air-exposed group. The iNOS induction generates a significant amount of NO leading to excess production of reactive oxygen species, injurious to various organs. An increase in iNOS protein and mRNA expression in the myocardium has been reported in mice to play a significant role in genotoxicity of certain drugs like Doxorubicin.
WPS associated genotoxicity causing pulmonary dysfunction is not reported with direct evidence but is supported by the fact that smoking-promotes oxidative DNA damage response which is highly correlated to lung carcinogenesis. WP smokers are reported with marked reduction in lung function parameters i.e forced expiratory volume in 1 s (FEV1), forced expiratory ratio (FEV1/FVC%), forced expiratory flow (FEF-25%), FEF-50%, FEF-75%, and FEF-75%–85% which are important parameters to identify early lung damage. Fractional NO in exhaled breath which is important in assessing the severity of pulmonary inflammation and asthma was also significantly reduced in WP-smokers compared to normal control. Chronic obstructive pulmonary diseases was augmented in Chinese WP-smokers. Cardiopulmonary effects of WPS sharing its genotoxicity can be traced directly through molecular basis or indirectly through clinical studies.
Obstetric and perinatal complications
Common obstetric and perinatal complications linked with WPS are infant mortality, low birth weight (LBW), low APGAR scores, and pulmonary toxicities. Genetic abnormalities are among the etiological factors responsible for these complications. Nuwayhid et al., 1998 reported that women in her first trimester lavishing one or more WPS per day deliver under weight infants (i.e., reduction of 100 g weight compared to normal individuals). This fact is in line with report of Nematollahi et al., 2018 who unveiled 2-fold increased risk of LBW in WP smokers owing to maternal CO exposure during pregnancy.
Also premature labor, placental disruptions, malformations, perinatal complications, and genetic disorders in the children of WPS mothers are invincible.,, Tamim et al., 2008 recited that smoking narghile (>1/day) amplifies 2.4 folds the odds of LBW, compared with nonsmokers. LBW babies born to rural women from southern Iran relishing on WPS was reported, while the effect was more pronounced if smoking sessions were conducted during first trimester. Wahabi et al., 2013 conducted a retrospective cohort study to probe the effects of secondhand tobacco smoke during pregnancy on newborns' anthropometry. He found significant reduction in birth weight (35 g) and length (0.261 cm) of infants born to exposed mothers as compared to the infants of unexposed mothers. It has proved to have genotoxic effects on chromosomes of human fetal cells. Children exposed to waterpipe smoking at home have been shown to have higher levels of carcinogenic TSNAs. Adding to the misery, those born with intrauterine growth retardation have preeminent incidence of hypertension, coronary heart disease, stroke and Type 2 diabetes mellitus in adult life.In vitro studies on nicotine toxicity report increase in the induction of DNA strand breaks in human spermatozoa, aneuploidy, and polyploidy, SCE and chromosomal aberrations in bone marrow cells of mice. Interference with oocyte maturation and chromosome disjunction was also reported. The effect of WPS on the embryo at the early stage of development was also studied using chicken embryos (at 3 days of incubations). The outcome of WPS on angiogenesis was studied using the chorioallantoic membrane (CAM) of the chicken embryos. It was concluded that WPS inhibits angiogenesis of the CAM. Around 80% of WPS-exposed embryos died before 10 days of incubation. Furthermore, WPS induced upregulations of BCL-2, Caspase-8, ATF-3, INHIB-A, and Cadherin 6 genes, which are important key regulators of cell apoptosis, proliferation, and migration. The study revealed embryonic death can occur via the deregulation of several genes related to cell apoptosis, proliferation, and migration.
Metabolic syndrome, blood dyscrasias and oral hygiene
Certain metabolic disorders have strong genetic basis. Linkage analysis, genome-wide association studies, candidate gene association studies, microRNAs, the study of epigenetics, long noncoding RNAs, system biology, next-generation sequencing, and whole-exome sequencing have been conducted to investigate the genetic determinants of the metabolic syndrome (MetS). An association for eight SNPs, which mostly are located in genes, involved in lipid metabolism are reported with MetS. Shafique et al., 2012 investigated correlation between WPS and MetS and found higher susceptibility of WP smokers towards hypertriglyceridemia, hyperglycemia and abdominal obesity. The study highlights significant negative impact of WPS on MetS. Although the genetic link between WPS and MetS was not focused in this study but it directs the investigators to recognize numerous chromosomes, various DNA polymorphisms in candidate genes and many gene variants, that are associated with MetS as an entity or its traits, related mostly to lipid metabolism. WPS results in impaired platelet function, including hemostatic changes and long-lasting oxidation injury. Wolfram et al., 2003 elucidated effect of WPS on the (iso) eicosanoid system, a marker of oxidation injury. The levels of 8-epi-PGF2α (P = 0.003), MDA (P = 0.001), and 11-DH-TXB2 (P = 0.0003) were escalated after a single smoking session and were further increased upon repeated exposures. Urinary albumin excretion is a very sensitive marker of renal injury and its role has also been recognized in possibility of cardiovascular diseases in normal and diabetic persons. Ishtiaque et al., 2014 reported a correlation between WPS and albuminuria unassociated with age at baseline, sex, BMI, social class, hypertension, and diabetes mellitus.
WPS has detrimental effect on mouth like staining of teeth, dental restorations, and reduced ability to smell and taste and is prominent risk factor for periodontal bone loss, dry sockets, submucous fibrosis, and oral squamous cell carcinoma., A Tunisian study reported higher plaque index for exclusive narghile smokers compared to exclusive CSs, while both carried same risk for reduction in periodontal bone height, a marker for periodontal bone loss. WPS carries the risk of transmitting microorganisms. Mycobacterium tuberculosis, hepatitis, and Helicobacter pylori are reported to be transmitted via mouth piece. [19,104-106] Virus can be mutagen that changes the genetic material and likely to be carcinogen. Alike hepatitis C virus, Epstein–Barr virus, herpes simplex virus and fungal species e.g., aspergillosis are also at the helm of transmission within WPS consumers.,, The role of certain viruses is well established in genotoxicity.
| Conclusion|| |
The water pipe (shisha, hookah, and narghile) is a centuries old method of tobacco use that had gradually rooted in almost all societies and is growing in Arabian counties including Saudi Arabia like an epidemic. Ironically, it is conceived as harmless compared to CS which is against the scientific findings. Its practice is most alarming in females of child bearing age due to its proven fetal damage and genotoxicity. Educational interventions to change perception of people, especially of women regarding the hazard of smoking shisha and at the same time teaching them effective approaches enabling to quit, would contribute to reducing WP incidence, especially at home, which in turn would have also a positive impact on the second hand smokers and children who live with WP smokers and later develop the habit.
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Conflicts of interest
There are no conflicts of interest.
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