Research Article
Volume 2 Issue 6 - 2015
Impact of Passive Smoke on Tongue Blood Vessels, Blood Cell Count and Blood Glutathione Level (Experimental Study)
Rasha H Al-Serwi1, Samah H Elmeadawy2 and Lobna RS Radwan1*
1Department of Oral Biology, Faculty of Dentistry, Mansoura University, Egypt
2Departments of Oral Medicine and Periodontology, Faculty of Dentistry, Mansoura University, Egypt
*Corresponding Author: Lobna RS Radwan, Department of Oral Biology, Faculty of Dentistry, Mansoura University, Egypt.
Received: September 19, 2015; Published: November 05, 2015
Citation: Lobna RS Radwan., et al. “Impact of Passive Smoke on Tongue Blood Vessels, Blood Cell Count and Blood Glutathione Level (Experimental Study)”. EC Dental Science 2.6 (2015): 423-434.
Abstract
Introduction: Passive smoke has found to produce local and systemic effects and impair the function of many organs. Passive smoke or second hand smoke is an involuntary exposure to the burn off end of the cigarette smoke which is directly released to the environment. Passive smokers can face the same health problems as smokers.
Aim of the work: To evaluate the effect of passive cigarette smoke on the tongue blood vessels in rats and investigate its effect on blood cell count and glutathione level in blood.
Materials and methods: 30 male Wister albino rats were used and divided into three groups (ten in each): Group I, control group. Group II & III exposed to passive cigarette smoke in closed smoking device (4 cigarettes twice daily) for 30 days and 60 days respectively. Complete blood cell count and glutathione level were measured. The animals were euthanized, tongue specimens were taken, prepared for histological (H & E and Trichrome stain) and immunohistochemical study for detection of α-smooth muscle actin.
Results: Tongue blood vessels exposed to passive smoke showed abnormal dilated blood vessels congested with blood, degenerating endothelial cells and decrease in the pericytes all around the blood vessel. Also, destruction and loss of the subintimal collagen layer were detected with Gomori’s trichrome stain. Immunohistochemical study revealed mild to minimum immunoreaction for α SMA on the blood vessels wall in comparison with the intense reaction of the control group. There were significant increases of WBCs count, RBCs count, Hb concentration and hematochrit values in passive smoke. Also, there was significant decrease in glutathione levels.
Conclusion: Passive smoke may lead to blood vessel damage, significant changes in blood cells and glutathione levels. These changes may lead to greater risk for developing atherosclerosis and cardiovascular diseases.
Keywords: Glutathione; Passive smokers; Cigarette smoke; Hematochrit value; Immunohistochemical study
Introduction
Smoking is the leading cause of morbidity and mortality in the developed world, causing over 4.8 million deaths per year globally [1]. Morbidity and death rate are likely even higher than current knowledge, due to the largely unknown drawbacks of passive smoke [2]. Active smoking is a hazard factor for conditions including cardiovascular disease, respiratory tract infection, lung, tracheal and bronchial cancers, mucosal alternations and periodontitis [3-8].
Passive smoking has found to produce local and systemic effects and to impair the function of many organs. Passive smoke produces the impairment of the growth and development of children, and increases the incidence of cancer [9], respiratory tract infections in children [10,11], premature vascular aging, and sudden infant death [12]. As regards to the effect of passive smoking on oral tissues, it was found to be associated with periodontal diseases [13,14], caries, alterations in salivary flow rate and protein levels and decrease in salivary PH in children [15].
Cigarette smoke contains over 4000 chemicals, many of which have toxic, carcinogenic effects on different biological systems [16]. Nicotine, the most pharmacologically active compound, is mostly absorbed through the lung alveoli. It is also absorbed in sufficient amount even in a slower rate through the oral mucosa to have a pharmacological effect [17].
Smoking increases the heart rate, cardiac output, and blood pressure and produce peripheral vasoconstriction by autonomic stimulation [18]. Moreover, nicotine also acts directly on blood vessels and capillaries to produce vasoconstriction [19]. Evidence suggests that smoking cause compromised vasodilatation, decreased blood flow to gingiva due to the direct vasoconstricting actions of nicotine [20,21]. Another study used a laser Doppler technique to measure gingival blood flow, and its results showed that smoking doesn’t compromise blood flow in the periodontal tissues [22]. Thus, there might be some controversy regarding the effect of tobacco consumption on the gingival blood vessels.
Cigarette smoke contains a large number of free radicals [23]. Free radical may be defined as “any species capable of independent existence that contains one or more unpaired electrons.” Reactive oxygen species (ROS) have the ability to produce direct damage to proteins, DNA, carbohydrates and lipids [24]. The main targets of reactive oxygen species (ROS) are polyunsaturated fatty acids present in membrane lipids causing lipid peroxidation and malondialdehyde (MDA) is formed [25].
The antioxidants as vitamin-E, vitamin-C, glutathione peroxidase and superoxide dismutase prevent tissue damage induced by free radicals [26]. Glutathione peroxidase reduces hydrogen peroxide and/ or lipid hydrogen peroxides by the oxidation of reduced glutathione or s-nitrosoglutathione [27]. In inflammatory diseases and periodontitis, reduced levels of GSH are detected [28], indicating the involvement of oxidative stress. GSH depletion is also associated with the augment of a pro-inflammatory signal by up-regulating ROS [29].
Therefore, the present study was aimed to evaluate the effect of passive cigarette smoke on the tongue blood vessels in rats and investigate its effects on blood cell count and glutathione level in blood.
Materials and Methods
Animals
Thirty male Wister albino rats (200-250g) were used in this study. The rats were housed in an animal house under standard laboratory conditions (temperature of the room: 22 + 2, humidity: 55 + 5L and 12 hours light\dark cycle). They were allowed commercial standard diet and water ad-libitum.
Experimental protocol
Rats were divided into three groups 10 rats in each: Group I, control group. Group II, exposed to cigarette smoke (Cleopatra) in closed smoking device (4 cigarettes twice daily) for 30 days. Group III, exposed to cigarette smoke (Cleopatra) in closed smoking device (4 cigarettes twice daily) for 60 days.
Smoking device
Closed glass container with ventilation hole at the top and attached metal tube to one side by which main stream of cigarette enters the device and another opening at the top for handling of rats before and after exposure.
Laboratory assessment
Blood samples were taken for complete blood cell count and glutathione level estimation [30].
Histological study
The animals were euthanized; tongue specimens were processed for histological evaluation by routine H&E and Gomori's trichrome stains for detection of collagen fibers. Immunolabeling of a-SMA was performed using the Dako kit. After deparaffinization of the sections in xylene, the sections were rehydrated in ethanol and water. The sections were immersed in 0.1% H2O2 for 30 minutes to avoid the activity of the endogenous peroxidase enzyme. Then the sections were washed with phosphate-buffered solution (PBS) and were immersed in ethylene diaminetetraacetic acid (EDTA) buffer or sodium citrate for 10 minutes at 95ºC. Then the sections were cooled to room temperature and were incubated for 20 minutes in 10% normal goat serum to avoid the background activity. After the addition of primary antibodies for (α-SMA), the sections were incubated with mouse or rabbit secondary antibody for 30 minutes at room temperature, and washed in PBS. Finally the sections were stained with diaminobenzidine tetrahydrochloride solution (DAB), and counter-stained with hematoxylin [31].
Statistical analysis
Data expressed as mean ± SD In the statistical comparison between the different groups, the significance of difference was tested using student's t-test to compare between mean of two groups of numerical (parametric) data. Pearson correlation coefficient® test was used to correlate different parameters. A P value < 0.05 was considered statistically significant. Analysis was done using the computer program SPSS (Statistical package for social science) version 17.
Results
Histological results
Hematoxylin and eosin stain findings
Group I, showed normal architecture of the blood vessels with endothelial cells lining and normal pericyte arrangement Figure 1A. Group II, showed dilated blood vessels, congested with blood, degenerating endothelial cells with loss of their nuclei and decrease in the pericytes all around the blood vessel Figure 1B. Group III, showed abnormal wavy surface, enlarged and engorged blood vessel with increase the loss of nuclei in the endothelium and the absence of the pericytes in most parts of the blood vessels Figure 1C.
Gomori's trichrome stain findings
Group I showed normal arrangement of the collagen fibers stained light green in the subintimal region and the muscles stained red (Figure 2A). Group II, showed destruction of the subintimal collagen layer Figure (2B) Group III, showed significant loss of the subintimal collagen Figure 2C.
Immunohistochemical Findings
Group I, showed intense immunoreactivity for α SMA in the blood vessel walls Figure 3A. Group II, showed mild immunoreaction for α-SMA in the blood vessel walls, Group III, showed minimum immunoreaction for α-SMA in the blood vessel walls.
Figure 1: (1A) Photomicrogragh of group I, showing normal architecture of the blood vessels with endothelial cells lining (arrow) and normal pericyte arrangement (arrow head).
(1B) Photomicrogragh of group II, showingdilated blood vessel ,congested with blood, degenerating endothelial cells with loss of their nuclei (arrow) and decrease in the pericytes all around the blood vessel (arrow head) .
(1C) Photomicrogragh of group III, showing abnormal wavy surface, enlarged and engorgement blood vessel with increase the loss of nuclei in the endothelium (arrow) and absence of the pericytes in most parts of the blood vessels (arrow head). (H&E X 400).
Figure 2: (2A) Photomicrogragh of group I showing normal arrangement of the collagen fibers stained light green in the subintimal region and the muscles stained red .
(2B)Photomicrograph of group II, showing destruction of the subintimal collagen layer (arrows ).
(2C) Photomicrograph of group III, showing significant loss of the subintimal collagen (arrows ) (Gömöritrichrome X 400).
Figure 3: (3A) Photomicrogragh of group I, showing intense immunoreactivity for α SMA in the blood vessel wall.
(3B) Photomicrogragh of group II, showing mild immunoreaction for α SMA in the blood vessel wall.
(3C) Photomicrogragh of group III, showing minimum immunoreaction for α SMA in the blood vessel wall. (IHC X 400).
Laboratory Results
There were significant differences in WBCs, HB concentration, RBCs, and hematochrit value of smokers after 30 days and non smokers with p values = 0.00001, 0.006625, 0.001 and 0.008563. There was non significant difference between platelet count of smokers after 30 days and non smoker (P = 0.6883). While after 60 days of passive smoking, there were significant differences between WBCs, HB, RBCs, hematochrit, and platelet counts of smokers and non smokers (P < 0.00001, 0.000353, 0.000142, 0.021663, and 0.000114). There were significant differences between glutathione levels of smokers after 30 days and 60 days and non smokers (P < 0.00001) and there was a non significant difference between glutathione level of smokers at different times (P = 0.6) (Table 1).
Time Smoking Mean Std. Deviation P value
30 day WBCS Non smokers 6290.2865 1001.19870 <0.00001
Smokers 15611.2109 2396.69998
Hb Non smokers 9.0103 1.91767 0.006625
Smokers 11.9368 2.32831
RBCs Non smokers 4440336.3881 819250.53016 <0.001
Smokers 6939426.4710 1198469.30958
HCT Non smokers 32.8804 8.81385 0.008563
Smokers 44.3919 8.63537
Platelet Non smokers 502877.4302 99425.02909 0.6883
Smokers 522304.0966 113234.63917
Glutathione Non smokers 0.1557 0.0178 <0.00001
Smokers 0.0881 0.0158
60 day WBCS Non smokers 6290.2865 1001.19870 <0.00001
Smokers 15585.2545 1924.34632
Hb Non smokers 9.0103 1.91767 0.000353
Smokers 15.2196 4.04010
RBCs Non smokers 4440336.3881 819250.53016 0.000142
Smokers 7269497.2334 1671941.39824
HCT Non smokers 32.8804 8.81385 0.021663
Smokers 42.4489 8.19539
Platelet Non smokers 502877.4302 99425.02909 0.000114
Smokers 745381.4885 120658.87905
Glutathione Non smokers 0.1557 0.0178 <0.00001
Smokers 0.0990 0.0197
Table 1: Effects of passive smoking on blood cell counts, HB concentration, haematocrit value and glutathione level.
Discussion
Cigarette smoke contains more than 4000 substances, many of which have toxic, carcinogenic effects on different biological systems [17]. In this study, smoking was found to be associated with dilated blood vessels which were congested with blood. This result was coincidental with the results of another study that assessed gingival blood flow using laser Doppler and they found that smoking does not compromise blood flow in the periodontium [23]. Muller et al found that smoking produces vasoconstriction of blood vessels that is preceded by vasodilatation. Moreover, they suggested that the produced effect may be due to the degree of inhalation of the tobacco smoke and the rate of nicotine absorption [32].
This vasodilatation effect of smoking shown in this study was in contrast with another study that found that nicotine produce vasoconstriction by activating the sympathetic ganglia to secrete catecholamine [33] which affect the alpha-receptors on blood vessels or by acting directly on blood vessels and capillaries [20]. Another study showed the vasoconstrictive direct effect of the tar component of the smoke on the capillaries [34]. This vasoconstrictive effect of nicotine may be responsible for the decreased clinical signs of gingival inflammation such as redness, exudation and bleeding in smokers. Another study found that gingival bleeding was decreased in smokers than in non smokers due to vasoconstriction of gingival vessels [35,36]. Passive smoke has dose- related impairment of endothelium-dependent dilatation in healthy young adults suggesting early arterial damage [37].Essentially, some of the reported effect discrepancies of smoking can be explained by the use of different preparations and concentration of cigarette smoke chemicals and different cell types by different studies.
The destruction of the subintimal collagen layer of smoker shown by Gomori's trichrome stain may be due to the effect of nicotine that stimulates collagenase enzyme and decrease type I collagen [38]. Another study mentioned that nicotine exposed fibroblast showed decreased growth rate, abnormal shapes, alternations of microtubules, vimentin and other cytoskeletal elements. Additionally, Nicotine decreased cell-signaling molecules and decreased cell migration rates by 50% in cultured gingival fibroblast cells compared with controls [39].
The degenerative changes and death of vascular endothelium may be due to the deposition of smoke chemicals. These degenerative changes occur in the form of reversible contraction of endothelial cells, which is mediated by oxidation and the collapse of the tubulin system [40]. Cigarette smoke’ chemicals were found to induce different forms of cell death as necrosis, programmed necrosis, autophagy and apoptosis [41]. Recent data indicate that cadmium present in cigarette smoke may contribute to endothelial cell death [42,43]. The changes of endothelial cell structure and the trigger of cell death decrease endothelial functions and may play a role in thrombogenic events [41].
Passive cigarette smoke induced decrease immunoreactivity for α SMA on the blood vessel wall . This was in contrast to previous study on pulmonary vascular remodelling in smokers and patients with mild chronic obstructive pulmonary disease (COPD), cigarette smoke induced thickened intima and positive immunoreactivity to α‐SMA antibody [44]. This is might be explained by Magnus study that demonstrated increased expression of α-SMA positive cells in the large airways in COPD, which was not related to smoking, but to the presence of airway obstruction [45].
In the present study, the glutathione level in passive smokers after 30 and 60 days was significantly lower than that of non smokers. This result was coincidental with Singh et al who found that smoking significantly decreases the levels of reduced glutathione and total antioxidant activity in coronary artery disease patients [46]. Furthermore, Abdelghany., et al. [] showed that exposure of Bovine aortic endothelial cells to cigarette smoke extract at different concentrations for two hours decreased NO production with a concomitant increase in O2– generation and depletion of cellular reduced glutathione [47]. 28-day second hand tobacco smoke exposure was found to be associated with increased oxidative stress [48].
The reduction of the glutathione antioxidant in smokers may be the result of their consumption in response to increased oxidative stress produced by cigarette smoke. Moreover, Serebreni et al. 2014 concluded that cigarette smoke increased oxidative stress inducing apoptosis in endothelial cells [49] and other studies detected that the accumulation of nicotine and heavy metals in the cells, inducing genetic alterations, amongst others [50,51].
This may explain that smoking increases the oxidative stress, which may be responsible for tissues destructions.
In this study, it was observed that passive smokers have higher blood WBCs counts than do non-smokers. This result was in accordance with the study of Song et al, who found that smokers have high peripheral blood PMNs levels [52]. Another study reported that smokers had increased levels of neutrophils, lymphocytes, and monocytes when compared with non smokers [53].
Smokers had significantly elevated white blood cell counts, which was correlated to the atherosclerotic plaque formation in the carotid artery [54]. Therefore, smoking was found to affect and stimulate the immune system, both systemically and locally. Systemic immunologic alterations induced by smoking were found to correlate with localized inflammation and increased expression of matrix metalloproteinase, which lead to atherosclerotic plaque formation in the vascular wall [55]. Moreover, not only active smokers can produce proinflammatory systemic effects, but also passive smokers showed increased inflammatory markers concentrations [56].
Passive smoke was found to be associated with increased number of platelets after 60 days of passive smoke. This result was in accordance to the results of numerous studies that reported that cigarette smoke stimulates platelets, activates the coagulation cascade, and decreases fibrinolysis [57,58]. Another study found that smoking increases the number, activates platelets, increases adhesion molecule expression on the surface of endothelial cells and induces the proatherogenic cytokine release, such as interleukin-6 and interleukin-8 [59]. Therefore, smokers showed a significant shift toward a prothrombotic state in the vascular wall [60].
Finally, passive smoke resulted in significant increase in RBCs, Hb concentration and haematocrit Hct (erythrocyte volume fraction which depends on the number and size of RBCs). These results were in agreement with other studies which investigated the smokers had significantly higher levels of white blood cells, red blood cells, haemoglobin and haematocrit [61-63]. These results can be explained as the smoke causes a persistent state of hypoxia due to smoke contents which cause an increase in erythrocyte count and Hb [62]. These changes might lead to greater danger for developing polycythemia vera, atherosclerosis, chronic obstructive pulmonary disease and\or cardiovascular diseases [61].
Conclusion
In conclusion, passive smoke might lead to blood vessel damage and significant changes in blood cells. It was noticed that the glutathione antioxidant level was significantly lower in passive smokers than non-smokers. Thus, smoking might play a role in enhancing oxidative stress. Also, passive smokers showed higher blood WBCs and platelet counts than do non-smokers which may increase the incidence of atherosclerotic plaque formation and thrombotic state in the vascular wall. So far active and passive smoke has dangerous effects and should be avoided and prevented.
Acknowledgment
We gratefully acknowledge Prof. Dr. Youssry M El-Hawary Prof. of Oral Biology, faculty of dentistry, Mansoura University for his help, effort and revision of this study and thanks to Mona Hassaan senior teaching assistant for her help in this research.
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Copyright: © 2015 Lobna RS Radwan., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047


EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560


EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318


EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819


EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840


EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344


EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476


EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658


EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489


EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278


EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108


EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571


EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333


EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883


EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001


EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937


EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723


EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726


EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603


EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646


EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616


EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290


EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226


EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812


EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268


News and Events


August Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the August issue of respective journals and can be viewed in the current issue pages.

Submission Deadline for September Issue

Ecronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the September issue of respective journals. Submissions are accepted on/before August 21, 2020.

Certificate of Publication

Ecronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

Ecronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.

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