Cigarette smoking effect on human health and ... - Dr. DS Kothari

Asian Pacific Journal of Tropical Biomedicine (2012)1-61Contents lists available at ScienceDirectAsian Pacific Journal of Tropical Biomedicinejournal homepage:www.elsevier.com/locate/apjtbDocument heading<strong>Cigarette</strong> <strong>smoking</strong> <strong>effect</strong> on human health and promising remedy bymangrovesChinnappan Ravinder Singh * , Kandasamy KathiresanCentre of Advanced Study in Marine Biology, Faculty of Marine Sciences, Annamalai University, Parangipettai- 608 502, Tamil Nadu, IndiaARTICLE INFOArticle history:Received 24 July 2012Received in revised form 7 August 2012Accepted 28 September 2012Available onlineKeywords:MangrovesLung cancerAnti-cancer drugsPhytochemicalsNicotiana tobacumABSTRACTThis article reviews the evils of cigarette <strong>smoking</strong> and the promise of mangroves to cure them.Chemicals in cigarette smoke are leading cause of death to both smokers and non-smokers. Plantis the potential source to produce medicine for almost all the diseases. Mangroves are promisingas a novel source of anti-cancer drugs in regulating the cancer pathways and stimulatingimmunity in the body system. Research on medicine from mangroves for the treatment of cancerhas not only been shown to an <strong>effect</strong> of cancer, but also provided important methods for the studyof cancer therapy and mechanism. This report may helps to explore the medicinal properties ofthe mangroves.1. IntroductionTobacco is regarded as “holy herb” and “God’sremedy”[1]. The genus Nicotiana belongs to the botanicalfamily Solanaceae with characteristic viscid foliage andtubular flowers. There are more than 60 species of thegenus, differentiated based on size and shape of leaves andflowers[2]. Nicotiana tobacum (N. tobacum) is an indigenousspecies to South America, while N. rustica to the WestIndies. Nicotin is a volatile, colourless and oily liquid withpoisonous alkaloid, which differentiates Nicotiana fromother plants.Tobacco causes human deaths, more than by all deathsfrom human immunodeficiency virus (HIV), illegal druguse, alcohol use, and motor vehicle injuries, suicides, andmurders combined[3]. Smokers die 14 years earlier thannonsmokers[4]. Tobacco <strong>smoking</strong> is a leading cause ofhuman cancer and deaths which are higher in developingcountries than in developed countries. About 70% of*Corresponding author: Dr. Chinnappan Ravinder Singh, UGC Dr.D.S. Kothari PostDoctoral Fellow, Centre of Advanced Study in Marine Biology, Faculty of marinesciences, Annamalai University, Parangipettai- 608 502, Tamil Nadu, India.Tel.: 09597992543Fax: 91-4144243555E-mail: chinnaravinder@yahoo.co.intobacco-related deaths will occur in developing countries[5].About 1.3 billion smokers worldwide and half of them diedue to <strong>smoking</strong>-related diseases[6]. About 13.3% of totaldeaths are expected in the year 2020 due to tobacco use[7].About 50% of all smokers will be killed by use of tobacco[8].Tobacco <strong>smoking</strong> is causing over 3 million deaths everyyear worldwide, and if current <strong>smoking</strong> trends continue theannual mortality will exceed 10 million by 2030[9].<strong>Cigarette</strong> <strong>smoking</strong>, particularly beedis and chewingtobacco (smokeless use), is an age-old practice in India.However, the popularity of <strong>smoking</strong> among women andyoung children has increased recently many folds and is asignificant public health problem[10]. In India alone, nearly1 in 10 adolescents initiate tobacco use before 10 years ofage. About 47% of the Indian males and 14% of the Indianfemales are tobacco users. Every year about 850 000 newcancer cases are diagnosed, resulting in India about 580 000cancer related mortality[11]. Realising the seriousness of<strong>smoking</strong>, the present review has been prepared to analyzethe status of issue.2. Toxic chemical composition of cigarette

2C. Ravinder Singh, K. Kathiresan./Asian Pacific Journal of Tropical Biomedicine (2012)1-6Tobacco is grown and sold in many countries. The largestproducers of tobacco are China, USA, the former SovietStates, Brazil and India. <strong>Cigarette</strong>s are made from driedleaves of the tobacco plant. The chemical composition oftobacco varies widely with different sites due to the diversityof climatic conditions. Even within the same tobacco, thechemical composition of different leaves can be significantlydifferent[12]. Chlorophyll a and b, neoxanthin, violaxanthin,lutein and 毬 - carotene are also present in N. tobacum[13].After the leaves of the tobacco plant are harvested anddried, they are treated with many chemicals. <strong>Cigarette</strong>smoke contains over 4 000 different chemicals and many ofthem cause cancer[14,15]. The cigarette smoke contains blacksticky tar that contains toxic chemicals such as ammonia,toluene and acetone. Tar is the main cause of throat and lungcancer. It also causes the yellowish brown stains on fingers,teeth and lung tissue. Nicotine is the major drug found intobacco which contributes to addiction to cigarette <strong>smoking</strong>which was first isolated from tobacco leaves as early as1828[16]. Nicotine has a number of harmful <strong>effect</strong>s on thehuman body in stimulating the nervous system, increasingheart beat, raising blood pressure and shrinking the smallblood vessels under the skin shrink, which can causewrinkles. Carbon monoxide is a poisonous gas that reducesthe amount of oxygen taken up by red blood cells. Hydrogencyanide damages the tiny hairs which act as natural lungcleaners of human bodies leading to accumulation of toxicsubstances in the lungs. The toxic heavy metals found inthe cigarette smoke are: lead, nickel, arsenic and cadmium.Cancer-causing radioactive compounds are also found incigarettes. Pesticides like DDT and methoprene do presentin tobacco smoke which is used during tobacco cultivation.Other chemicals such as benzene, creosote, and someasphalts cause skin cancer, lung cancer and reduction inreproductive capacity. Among the 2 256 different smokecomponents, 542 find place in conventional smoke by acigarette[17]. The highly carcinogenic compounds suchas dimethylbenz(a)anthracene, dimethylnitrosamine andmethylnaphthalene are added when the cigarettes are beingmade[18].2.1. <strong>Cigarette</strong> <strong>smoking</strong> and cancerCancer-related death was estimated at 100 million in20th century and is 1 billion in 21st century[19]. Cancerprevalence in the United States is about 300 cases per 100 000populations, whereas that in Asian countries is less than 100cases per 100 000 due to tobacco smoke[20]. It is estimatedthat in 2015, tobacco is projected to kill 50% more peoplethan HIV/AIDS and will be responsible for 10% of all deathsglobally[21]. Over 3 000 teenagers light up the cigarette for thefirst time every day[22]. In India, the International Agency forResearch on Cancer estimated that about 635 000 people diedfrom cancer in 2008, representing about 8% of all estimatedglobal cancer deaths and about 6% of all deaths in India[23].The temperature estimated at glowing tip of lighted cigaretteburning is 800 曟 . A smoker with each puff draws into hismouth and lungs, a hot collection of gases and many toxic1100 0001 000 000900 0001 020 000900 000800 000700 000600 000500 000500 000443 000400 000300 000200 000100 000140 000110 000ChinaIndiaRussiaAmericaGermanyTurktyUKPakistan100 00090 00066 00065 00050 000FranceMexicoSpainlran50 00049 00044 00040 000South KoreaSouth AfricaVietnamCanadaEgyptRomaniaNo.of deaths/year(in thousands)Figure 1. Annual global death due to cigarette <strong>smoking</strong> related diseases.37 00034 00033 00020 00020 00019 00013 000PhillipinesGreeceAustraliaScotland13 00010 0006 000CroatiaMalaysialrelandCuba6 0005 0002 555New ZealandUruguay

C. Ravinder Singh, K. Kathiresan./Asian Pacific Journal of Tropical Biomedicine (2012)1-63particles[24]. Tobacco smoke may lead to changes in thelung tissue shortly after exposure, so called precancerouschanges. Tobacco-related cancers represent 11.45% malecancer deaths and there were twice as many deaths fromoral cancers as lung cancers in India[25]. Most of the lungcancer and emphysema, as well as a high percentage ofheart attacks are caused by cigarette <strong>smoking</strong>[26].Lung cancer is an aggressive and heterogeneous diseaseand most common malignant tumours worldwide[27-31]. Thelungs are the most important organs that help us breathe andgive oxygen to all the cells in the body. These organs affectdirectly or indirectly by cigarette <strong>smoking</strong>. Like all cancers,lung cancer cells have the ability to invade neighboringtissues and spread to distant parts of the body. It is usuallyclassified as non-small cell lung cancer (NSCLC), whichaccounts for more than 80% of lung cancers and it is the mostcommon cause of cancer deaths worldwide[32,33]. In women,lung cancer is the third-most common cancer worldwide,after breast and colorectal cancers[34]. Smokers are 5-10times likely to develop lung cancer, about 87% of lungcancer cases are caused by cigarette <strong>smoking</strong>[35]. Every year,one million smokers die of lung cancer in USA, accountingfor 25% of total <strong>smoking</strong>-related deaths (Figure 1). One in 10moderate smokers and one in 5 heavy smokers (15 cigarettesper day) will die of lung cancer. About 85% of smokers withlung cancer die within 5.5 years die within one year[36].Many types of cancers including pancreatic cancer andcolon cancer, bladder and kidney cancer are caused dueto tobacco <strong>smoking</strong>[37]. Tobacco <strong>smoking</strong> is also associatedwith cancer of the oral cavity (including lip and tongue) inboth men and women. <strong>Cigarette</strong> <strong>smoking</strong> causes not onlylung cancer, but also cancer in urinary tract, oral cavity,oropharynx and hypopharynx, oesophagus, larynx, pancreas,stomach, cervix, leukaemia, female breast and prostate[38].2.2. <strong>Cigarette</strong> <strong>smoking</strong> and human reproduction<strong>Cigarette</strong> <strong>smoking</strong> affects adversely human fertility[39].Chemical agents may affect male reproduction by means ofdirect <strong>effect</strong> on the testicular function and spermatogenesis.The mechanisms involve the hormonal control ofspermatogenesis or through direct <strong>effect</strong> upon the germcells and sertoli cells of the seminiferous epithelium. Suchalterations in the spermatogenetic capacity in the male maylead to infertility or production of mutated spermatozoawhich may subsequently cause poor pregnancy if themutated spermatozoa are to fertilize an egg. <strong>Cigarette</strong><strong>smoking</strong> causes different negative <strong>effect</strong>s on humanreproductive process such as abnormal sperm morphology,less motile sperm, smaller quantity of sperm, lowerproportion of normally shaped sperm and changes in thenumber and arrangement of the microtubules of the sperm ina smoker as compared to a non smoker group of men[40-44].Women are likely to have menstrual irregularities,infertility problems, cramps and hot flashes duringmenopause due to <strong>smoking</strong>. Smoking lowers the level ofestrogen and attains early menopause with increased risk ofosteoporosis and fractures[45]. <strong>Cigarette</strong> <strong>smoking</strong> can interferewith almost every aspect of egg production, fertilizationprocess, embryo attachment, growth and development of thebaby during the pregnancy. From the initial step of womanpregnancy, cigarette <strong>smoking</strong> causes a number of problemssuch as deleterious <strong>effect</strong>s on embryo transport, control ofoocyte production, embryo viability, onset of menopause andbone metabolism. The smoke affects both the mother andthe growing young ones. The smoke adversely affects boththe humoral and cellular immune systems. Such alterationsmight affect epithelial response to inflammation result inan increased frequency of tubal infection and subsequentinfertility. Possible early or deferred entry of blastocystinto the uterus and alterations in the immune system thatcan account for the <strong>smoking</strong> and decreased fecundity[46,47].Exposure to cigarette smoke during pregnancy is associatedwith low birth weight, premature delivery, early pregnancyloss, prenatal mortality, and ectopic pregnancy[48].2.3. Other harmful <strong>effect</strong>s of cigarette <strong>smoking</strong><strong>Cigarette</strong> <strong>smoking</strong> contributes to remarkable risk factorsof non-communicable diseases, including coronary heartdisease, stroke, chronic obstructive pulmonary disease,peripheral vascular disease, peptic ulcer disease andtuberculosis[49]. <strong>Cigarette</strong> <strong>smoking</strong> is strongly associated withlung cancer, emphysema, chronic bronchitis, cardiovasculardisease, and other serious internal diseases andcancers[50-54]. The non-stop chronic inhalation of cigarettesmoke alters a wide range of immunological functions,including innate and adaptive immune responses[55].3. Environmental impact of cigarette <strong>smoking</strong>Smoking of cigarettes causes a great concern ofenvironmental problems[56]. In the past 25 years, 52 907 756cigarette butts have been collected from internationalbeaches, accounting for 32% of all debris collected. Thenumber of cigarette butts collected is over three timesmore than that of other wastage[57]. These butts may thenbe carried as runoff to drains, making their way to riversand ultimately to oceans. Though the waste materials arebiodegradable, it will take a long time of nine months todegrade the cellulose acetate and plastic materials presentin the cigarette waste in the sewage water[58-60]. The studiesconducted in the aquatic ecosystems have reported that thenicotinic acid and ethyl phenol present in the cigarette buttsaffect the fish and microbial communities[61-63]. <strong>Cigarette</strong><strong>smoking</strong> releases about 2.6 billion kilograms of carbondioxide in the air every year and about 5.2 billion kilogramsof methane annually worldwide[64,65].4. Mangroves in cancer treatmentThe plant kingdom is potentially a very diverse source of

4C. Ravinder Singh, K. Kathiresan./Asian Pacific Journal of Tropical Biomedicine (2012)1-6chemical constituents with many bioactivity notably tumourcytotoxic activity. India has the richest source of medicinalplants among the world. About 25 000 <strong>effect</strong>ive plant deriveddrugs are used in folk medicine in India. There are 7 800drug manufacturing units, which exploit about 2 000 tonnes ofherbal plants every year in the country[66]. Natural productshave played a significant role in drug discovery anddevelopment, especially as agents active against cancer andinfectious diseases[67]. Several anticancer agents includingtaxol, vinblas-tine, vincristine, camptothecin derivatives,topotecan and irinotecan and etoposide are in clinical useall over the world[68].Traditional uses of mangroves recently attracted thescientific communities to find out the pharmaceuticalproducts to combat a number of serious diseases[69].Mangrove plants such as Avicennia africana, A. nitida,Bruguiera exaristate, Buddleja parviflora and Bruguierasexangula and some of the mangrove associates arealso used to cure the cancer diseases by the fishermencommunities[70,71]. The mangrove plants and their associatespossess a strong antioxidant activity as they grow in thestressful environment conditions. Excoecaria agallocha,Avicennia alba, Aegiceras corniculatum, Bruguieragymnorrhiza, Ceriops decandra, Rhizophora mucronata,Rhizophora apiculata, Rhizophora stylosa, Sonneratiaapetala, Acanthus ilicifolius, Ipomea pes-caprae, Sesuviumportulacastrum, Suaeda maritima, Heritiera fomes,Terminalia catappa and Pandanus odoratissimu possessthe free radical scavenging and anti-oxidant activity[72-78].Mangrove plants are a rich source of steroids, triterpenes,saponins, flavonoids, alkaloids and tannins[79]. Naturalproducts with antitumour properties can be classifiedinto 13 distinct chemical groups such as alkaloids,phenylpropanoids, terpenoids, aldehydes, glycosides,lignans, lipids, unsaponified lipids, nucleic acids,polysaccharides, proteins and unidentified compounds[80].About 32 plants, Acanthus ebracteatus, Acanthusillicifolius, Acrostichum aureum, Avicennia alba, Avicenniamarina, Barringtonia asiatica, Bruguiera cylindrica,Bruguiera gymnorrhiza, Buddleja parviflora, Bruguierasexangula, Ceriops decandra, Ceriops tagal, Cissuscarnosa, Cordia cochinchinensis, Cynometra ramiflora,Derris trifoliata, Flagellaria indica, Lumnitzera racemosa,Nypa fruticans, Phoenix paludosa, Rhizophora apiculata,Rhizophora mucronata, Sarcolobus globosus, Sonneratiaalba, Sonneratia caseolaris, S. ovata, Stenochlaena palustris,Suaeda maritima, Trianthema decandra, Weddelia biflora,Xylocarpus granatum and Xylocarpus rumphii exhibit theantioxidant and cancer chemoprevention activity[81]. In theyear of 2011, Kathiresan and his research team have provedanti-oral cancer <strong>effect</strong> of black tea extracted from themangrove plant Ceriops decandra[80]. Extracts of Bruguierasexangula bark are active against two tumours, Sarcoma180 and Lewis Lung carcinoma[82]. Twelve naphthoquinonesisolated from the mangrove Avicennia marina exhibit stronganti-proliferative activities against L-929 mouse fibroblastsand K562 human chronic myeloid leukemia cell lines[83].Xylocarpus granatum, Aegiceras corniculatum, Calophylluminophyllum and Excoecaria agallocha display the stronganti-proliferative <strong>effect</strong>[84].5. Concluding remarksIt is matter of necessity to develop potent drugs to treat<strong>smoking</strong> related diseases. It is a matter of urgency toconsider <strong>effect</strong>ive way for prevention of smoke-relatedcancers. In this regard, plant bioactive compounds areimportant in the treatment of cancers. Natural productscomprise of 14 out of the top 35 drugs on worldwide sales[85].There are more than 270 000 higher plants existing on thisplanet including mangroves but only a small portion hasbeen explored scientifically. So, it is anticipated thatplants can provide potential bioactive compounds for thedevelopment of new “leads” to combat cancer diseases.Finding remedy from natural sources is the only <strong>effect</strong>iveway to reduce the cancer diseases. In this regard, mangrovesare promising as a source of medicines. Further research iswarranted to develop potent drugs from the mangroves for<strong>smoking</strong>-related diseases in the following lines.Broad based screening of mangrove species extractedin different solvents of various polarities againstcarcinogenesis; isolation, purification and identificationof anti-cancer chemicals present in the potent extract;physical, chemical and biological characterizations of thebioactive compounds; formulation of mangrove-based drugsand testing their efficacy with standard drugs under in vitroand in vivo conditions; cost-benefits analysis for developingcommercial ventures.AcknowledgementsThe authors are thankful to the authority of AnnamalaiUniversity for providing facilities and Dr. C. Ravinder Singhto UGC for “UGC-Dr. DS Kothari Post Doctoral Fellowship”.References[1] Dickson SA. Panacea or precious bane. Tobacco in 16th centuryliterature. New York: New York Public Library; 1954.[2] Feinhandler SJ, Fleming HC, Monahan JM. 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