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The effect of smoking cigarette on kidney functions

Research Project

Submitted to the department of ( Chemistry ) in partial fulfillment of

the requirements for the degree of BSc. in (( Chemistry )

By

:Bushra Haider

Student name

Supervised by:

Lecturer name

May -2019

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ABSTRACT There are numerous harmful substances found in tobacco and tobacco smoke. Nicotine is one of these substances that may be acquired through active and passive smoking. In man nicotine is commonly consumed via smoking cigarettes. Therefore, the aim of this study is to elucidate whether smoking has effects on kidney functions in Sudanese young students. Eighty five subjects were included in this study, 30 none smoking males as the control group (healthy males) and the other 30 as smoker group, whom smoking more than 12 cigarette /day. Renal function tests were done for all participants; for investigates creatinine, urea and uric acid.Results: The results revealed that the levels of creatinine and urea were found significantly higher (P < 0.05), and the level of uric acid were found significantly decreased (P < 0.05) in smoker group when compared with the control group.Conclusions: The study concluded that, Smokers are at greater risk for kidney disease, which indicated by serum creatinine, urea, and uric acid.

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Contents…………………………………………………..……….Page

Abstract………………………………………………………………… Chapter one (Introduction)

1. Inrtoduction…………………………………………………………………………..2

1.1 History………………………………………………………………………………….………..3

1.2 Component of cigarette smoking……………………………………………………............4 1.3 Systemic effect of smoking………………………………………………………………...….8 1.3.1 cardiovascular system effects chemical………………………………………………..….8 1.3.2 Respiratory system effects……………………………………………………………….....8 1.3.3 Immune system effects………………………………………………………………..…….9

1.3.4 Musculoskeletal system effects………………………………………………………...…..9 1.4 Advers effects of smoking on the body………………………………………………………9 1.5 Advers effects of smoking on the liver……………………………………..…………..…..10 1.6 How does smoking affects the liver…………………………………………………………11

1.6.1 Toxic effects of smoking on the liver……………………………………………………..11 1.6.2 Direct toxic effects…………………………………………………………………………..11

1.6.3 Indirect toxic effects………………………………………………………...………………12 1.7 Smoker syndrome…………………………………………………………………………….12

1.8 Immunological effects of smoking………………………………………..…………………13 1.9 Oncogenic effects of smoking………………………………………………….……………14 1.10 Facts second hand smoke………………………………………………………………….14 1.10.1 The benefits of smoking cessation ……………………………..………………………15

1.11iver function test………………………………………………………………………………16

Chapter ( two material and methods) 2.1 Subjects, Samples, Chemicals ……………………….............................……………19

2.1.1 Subjects…………………………………………………………………………...……….19 .2- Methods…………………………………………………….. 2.2.1- Determination of uric acid ………………………….19 2.2.2- Determination of Serum Urea……………………………………………….19

2.2.3- Determination of Serum Creatinine………………….…22

Chapter Three 3- Results and Discussion……………………………………………………………………….26

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Chapter One Introduction 1. Introduction Cigarette smoking is a major cause of preventable morbidity and mortality[Funk et al.,2006]. Worldwide, more than 3 million people currently die each year from cigarette smoking [Aurelio et al.,2005]. The risk of death in the smokers measured by the number of cigarettes smoked daily, the duration of smoking, the degree of inhalation and the age of initiation[Janson et al.,2001]. Cigarette smoke contains over 4000 different chemicals, 400 of which are proven to be carcinogenic; it also contains various oxidants such as oxygen free radicals and volatile aldehydes which are probably the major causes of damage to biomolecules [Yeh et al.,2008]. Cigarette smoking yields chemical substances with high cytotoxic potentials [Yuen et al.,1995]. Cigarette smoke consists of many chemicals, including nicotine, tar with its many carcinogens, and gaseous compounds including carbon monoxide [Benowitz et al.,2007].Cigarette smoke also contains large numbers of free radicals that are capable of initiating or promoting oxidative injury[David et al.,1996]. Cigarette smokers are at greater riskor cardiovascular diseases, respiratory disorders, cancers, peptic ulcers and gastroesophageal reflux disease, blind-ness, bone matrix loss, and hepatotoxicity comparing with non-smokers [Spiro and silvestr.,2005]. Nephrologists “rediscovered” smoking as a major renal risk factor in 1997 [Ritz et al., 1997] although investigators in the 19th and 20th centuries had noted an association between smoking and renal damage [Lickint et al ., 1939]. In the past few years the knowledge about the renal risks of smoking has expanded rapidly. The patients who are at high risk to be affected by the adverse renal effects of smoking have been identified, and earlier observations in the 1970s and 1980s have been confirmed by prospective studies. never-smokers. Creatinine clearance was even slightly higher in current smokers, at least in men. This was also true when normotensive and hypertensive subjects were analyzed separately. The difference was, however, small. The effect of current smoking on creatinine clearance was reversible upon discontinuation of smoking. These data are compatible with the notion of early hyperfiltration. Data from the prospective Multiple Risk Factor Intervention Trial (MRFIT) which included 332,544 men, indicate, however, that smoking also increases the risk of renal failure in the general male population [Klag et al., 1996]. In a preliminary communication, a dose-dependent increase of the relative risk of end-stage renal failure (ESRF) was found in smokers as compared with nonsmokers (up to 1.69 for heavy smokers) [Whelton et al., 1995]. The increase in risk was independent of confounding factors. Unfortunately, the preliminary data on the relative risk of ESRF conferred by smoking have never been published as a full-size paper.

1.1 History

The history of smoking dates back to as early as 5000 BC in the Americas in shamanistic rituals. With the arrival of the Europeans in the 16th century, the consumption, cultivation, and trading of tobacco quickly spread. The modernization of farming equipment and manufacturing increased the availability of cigarettes following

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the reconstruction era in the United States. Mass production quickly expanded the scope of consumption, which grew until the scientific controversies of the 1960s, and condemnation in the 1980s. Cannabis was common in Eurasia before the arrival of tobacco, and is known to have been used since at least 5000 BC. Cannabis was not commonly smoked directly until the advent of tobacco in the 16th century. Before this cannabis and numerous other plants were vaporized on hot rocks or charcoal, burned as incense or in vessels and censers and inhaled indirectly. Evidence of direct smoking before the 16th century is contentious, with pipes thought to have been used to smoke cannabis dated to the 10th to 12th centuries found in Southeastern Africa. Previously eaten for its medicinal properties, opium smoking became widespread during the 19th century from British trade with China. This spawned the many infamous Opium dens. In the latter half of the century, opium smoking became popular in the artistic communities of Europe. While Opium dens continued to exist throughout the world, the trend among the Europeans abated during the First World War, and among the Chinese during the cultural revolution. More widespread cigarette usage as well as increased life expectancy during the 1920s made adverse health effects more noticeable. In 1929, Fritz Lickint of Dresden, Germany, published formal statistical evidence of a lung cancer–tobacco link, which subsequently led a strong anti-smoking movement in Nazi Germany. The subject remained largely taboo until 1954 with the British Doctors Study, and in 1964 United States Surgeon General's report. Tobacco became stigmatized, which led to the largest civil settlement in United States history, the Tobacco Master Settlement (MSA).

1.2Component of Cigarette smoking

1.2.1Nicotine

(C10H14N2) is a naturally occurring liquid alkaloid. An alkaloid is an organic compound made out of carbon, hydrogen, nitrogen and sometimes oxygen. Nicotine is a natural component of the tobacco plant leaf and is present in cigarettes in varying concentrations. Nicotine delivery from the smoke of a cigarette influences smoking behavior as the smoker is trying to meet their body's 'demand' for nicotine. If a cigarette has a low nicotine concentration then the smoker may draw from the cigarette more frequently and more deeply and inhale larger volumes of smoke. This, of course, means that they are also inhaling more of the other harmful components of cigarette smoke. * Nicotine is efficiently extracted in the lungs where it enters the circulatory system and is absorbed throughout the body. It easily crosses the blood-brain barrier and there are nicotine receptors throughout the central and peripheral nervous systems. Nicotine has multiple neurobiological effects and follows a variety of neurological pathways that control pleasure and reward within the central nervous system. It is an extremely addictive drug and stimulates its own taking by its neurobiological actions: nicotine's effects, the sensations of pleasure and wellbeing, produce rapid, positive reinforcement, i.e. the desire for more nicotine. Nicotine withdrawal causes physiological and behavioral changes including an increase in resting metabolic rate, a decrease in heart rate and feelings of

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aggression, irritability and insomnia. The withdrawal effects begin within 6 to 12 hours, peak at 1 to 3 days and can last over a month. * Nicotine is principally metabolized in the liver to cotinine, its main metabolite but some nicotine remains active for 6 to 8 hours, especially if the person regularly smokes another cigarette. Nicotine has various effects on the cardiovascular system. Although the effect of one dose of nicotine may be small and transient, repeated doses throughout the day can have a significant effect. Nicotine stimulates the release of the hormone adrenaline, increasing heart rate and blood pressure. It also stimulates the release of free fatty acids (an effect of adrenaline), increases fibrolytic activity and platelet activity.[Aosaki et al., 2007]

1.2.2 Carbon Monoxide - this is a poisonous gas. It has no smell or taste. The body

finds it hard to differentiate carbon monoxide from oxygen and absorbs it into the bloodstream. Faulty boilers emit dangerous carbon monoxide, as to car exhausts. If there is enough carbon monoxide around you and you inhale it, you can go into a coma and die. Carbon monoxide decreases muscle and heart function, it causes fatigue, weakness, and dizziness. It is especially toxic for babies still in the womb, infants and indifividuals with heart or lung disease.

1.2.3Tar - consists of several cancer-causing chemicals. When a smoker inhales cigarette

smoke, 70% of the tar remains in the lungs. Try the handkerchief test. Fill the mouth with smoke, don't inhale, and blow the smoke through the handkerchief. There will be a sticky, brown stain on the cloth. Do this again, but this time inhale and the blow the smoke through the cloth, there will only be a very faint light brown stain.

1.2.4 Ammonia (toilet cleaner): Ammonia, an alkali found in dry cleaning fluids is added

to cigarettes to speed the rate at which nicotine is absorbed through the blood stream and blood-brain-barrier. Ammonia raises the pH levels of smoke creating “free nicotine” which can be absorbed by the body more quickly than “bound nicotine”.

1.2.5 Hydrogen Cyanide (gas chamber poison)

1.2.6 Acetone (nail polish remover): Fragrant volatile liquid ketone, used as a solvent,

for example, nail polish remover.

1.2.6 Arsenic (rat poison)

1.2.8 Benzene (gas additive): A colorless cyclic hydrocarbon obtained from coal and

petroleum, used as a solvent in fuel and in chemical manufacture. It is a known carcinogen and is associated with leukaemia.

1.2.9 Polonium – 210 (Radon): a radioactive element found in smoke and is equivalent

to the radiation from 4 chest x-rays

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1.2.10 Formaldehyde (embalming fluid) A colorless liquid, highly poisonous, used to

preserve dead bodies. Known to cause cancer, respiratory, skin and gastrointestinal problems. · How can cocoa and licorice be harmful? When burned together they act as bronchodilators allowing greater amounts of smoke inhalation providing larger amounts of nicotine delivery. · Cocoa, along with other sweeteners are added to mask the taste of tobacco while menthol and other similar additives are used to anesthetize the throat so the smoker does not feel the irritating effects.[Prabha et al., 2015]

Figure(1) [Prabha et al.,2015]

1.3 Systemic Effects of Smoking 1.3.1 Cardiovascular System Effects

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Nicotine, one of the main compounds found in cigarettes exerts its effects on the cardiovascular system by stimulating the production of cateccholamines (epinephrine & norepinephrine) resulting in: 1. increased heart rate 2. elevated blood pressure 3. increased peripheral vascular resistance 4. increased myocardial oxygen demand [Gepner et al., 2011]. 5. tissue hypoxemia While there is a greater demand for oxygen, the carbon monoxide in cigarette smoke binds with the hemoglobin in the blood to form carboxyhemoglobin which reduces the supply of oxygen to the tissues by up to 15%. This results in a supply demand imbalance. Bermudez et al., 2012]. 6. increased plasma viscosity (polycythemia 2° to tissue hypoxemia from carbon monoxide) 7. elevated total cholesterol and LDL levels 8. increase fibrolytic and platelet activity.[Boekholde et al.,2012]

1.3.2 Respiratory System Effects 1. paralysis of mucociliary transport. (1 cigarette = ~ 20 minutes of paralysis!) 2. destruction of lung cilia leads to increased mucosal production. 3. small airway narrowing, reduced pulmonary surfactant and compliance mean less oxygen exchange and a tendency for a ventilation-perfusion (V/Q) mismatch [Gepner et al., 2011]

1.3.3 Immune System Effects 1. decreased neutrophil activity. 2. impaired immunity increases the risk for lung infection. 3. impaired wound healing attributed to the toxins in smoke which are the result of poor oxygen perfusion throughout the body. [David et al., 2008]

Musculoskeletal System Effects 1. increased risk of osteoporosis. 2. increased risk of fracture(s) with impairment of fracture healing smoking may impair (bone forming cells) function. Non-smokers produce approximately 1cm of bone in 2 months while it takes a smoker 3 months to make the same amount of bone. 3. increased risk of herniation of an intervertebral disc. It is suggested that smoking makes discs more susceptible to disease by affecting the blood supply to the discs.[Mayhan WG and Sharp., 2016].

1.4 Adverse effects of smoking on the body bone matrix loss, and Smokers are at greater risk for cardiovascular diseases

(ischaemic heart disease, hypertension), respiratory disorders (bronchitis, emphysema, chronic obstructive lung disease, asthma), cancer (lung, pancreas, breast, liver, bladder, oral, larynx, oesophagus, stomach and kidney), peptic ulcers and gastroesophageal reflux

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disease (GERD), male impotence and infertility, blindness, hearing loss and hepatotoxicity.[Mukaiya et al., 1998]

1.5 Immunological effects of smoking Smoking affects both cell-mediated and humoral immune responses[Sopori ML and Kozak.,1998]. Nicotine blocks lymphocyte proliferation and differentiation including suppression of antibody-forming cells[Mc Cue et al., 2000] by inhibiting antigen-mediated signaling in T cells[Geng et al., 1996]] and riboneucleotide reductase. Furthermore, smoking induces apoptosis of lymphocytes [Suzuki et al., 1999] by enhancing expression of Fas (CD95) death receptor which allows them to be killed by other cells expressing a surface protein called Fas ligand (FasL). Smoking induces elevation of CD8+ T-cytotoxic lymphocytes[Watanabe et al., 1995]], decreased CD4+ cells, impaired NK cell activity [Zeidel et al., 2002] and increases the production of pro-inflammatory cytokines (IL-1, IL-6, TNF-a) [Moszczynski et al., 2001]. Although smoking has long-term adverse effects; cessation of smoking reversed these effects, such as elevation of NK activity which is detectable within one month of smoking cessation [Meliska et al., 1995], elevation of both antibody- and cell mediated immune responses as well as decreased proinflammatory cytokines and increased Antioxid

1.6 Oncogenic effects of smoking Smoking yields chemicals with oncogenic potentials such as hydrocarbons, nitrosamine, tar and vinyl chloride [Helen et al., 1997]. Cigarette smoking is a major source of 4-aminobiphenyl, a hepatic carcinogen which has been implicated as a causal risk factor for HCC[4]. Smoking increases the risk of HCC in patients with viral hepatitis[Yu MW et al ., 1999]. Furthermore, recent data from China and Taiwan have shown an association of smoking with liver cancer independent of HBV status[Chen et al., 2003]. Tobacco smoking is associated with reduction of p53, a tumour suppressor gene[Wang et al., 2004] which is considered “the genome guardian”. Suppression of T-cell responses by nicotine and tar is associated with decreased surveillance for tumour cells. [EL-Zayadi et al., 2002] reported that heavy smokers accumulate excess iron in hepatocytes which induces fibrosis and favours development of HCC. Smoking is considered a co-factor with HBV and HCV for hepatocarcinogenesis[Alberty et al.,1999]. In addition, suppressed mood, a common feature among heavy smokers, increases the riskfor development of cancer.

1.7 Facts About Second Hand Smoke Secondhand smoke comes from two places: smoke breathed out by the perso n who smokes, and smoke from the end of a burning cigarette. Secondhand smoke causes or exacerbates a wide range of adverse health effects, including cancer, respiratory infections, and asthma. Secondhand smoke contains over 4,000 chemicals; 200 are poisons; 43 cause cancer.

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Secondhand smoke has been classified by the Environmental Protection Agency (EPA) as a known cause of cancer in humans (Group A carcinogen). Secondhand smoke causes lung cancer and other health problems. The EPA estimates that secondhand smoke causes approximately 3,000 lung cancer deaths and 35,000 heart disease deaths in nonsmokers each year. Secondhand smoke is especially harmful to young children. EPA estimates that secondhand smoke is responsible for between 150,000 and 300,000 lower respiratory tract infections in infants and children under 18 months of age annually, resulting in between 7,500 and 15,000 hospitalizations each year. Secondhand smoke is harmful to children with asthma. The EPA estimates that for between 200,000 and one million asthmatic children, exposure to secondhand smoke worsens their condition. Secondhand smoke can make healthy children less than 18 months of age sick; it can cause pneumonia, ear infections, bronchitis, coughing, wheezing and increased mucus production. According to the EPA, secondhand smoke can lead to the buildup of fluid in the middle ear, the most common cause of hospitalization of children for an operation.[Johan and Proyer., 2012]. 1.8 physiological functions of kidney The kidneys play a major role in the control of the consistency of the internal environment. The blood passing through the kidneys is first filtrated (glomerular filtration)sothatall theconstituents, except blood cells and plasma proteins, go into the microtubular systems. In the kidneys the useful substances are quickly reabsorbed but unwanted substances escape filtration and are actively excreted in urine [El Sayed et al., 2013]. However, renal function tests are important to identify renal dysfunction, to diagnose renal disease, to monitor disease progress, and to monitor response to treatment. In medicine (nephrology) renal function is an indication of the state of the kidney and its physiological role in the body. Most doctors use the concentration of creatinine, urea, to determine renal function. These measures are adequate to determine whether a patient is suffering from kidney disease.Smoking cigarette causes deterioration of renal function, which was first demonstrated in patients with kidney diseases, including* diabetic nephropathy,hypertensive nephrosclerosis, polycystic kidney, and glomerulonephritis in the last decade of the last century, with subsequent evidence accumulating even in the general population from communities [Noborisaka et al., 2007] Therefore, this study is aim to investigate the effects of smoking cigarettes on serum creatinine, urea, and uric acid. Participants eighty of younger universities students were included in this study. 1.8.1Creatinine - A waste product made by the muscles. It is usually removed from the blood by the kidneys and passes out in the urine. When your kidneys aren’t working well, creatinine stays in the blood. Creatinine varies with age, gender and body weight, so it’s not an accurate way of measuring overall kidney function. When on dialysis, creatinine levels are always high.

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1.8.2 Urea - A waste product made as the body breaks down protein. High urea levels

suggest decreased kidneyfunction.[Al sayde et al., 2013].

Figuer(2)[Noborisaka et al., 2007] 1.9 Effect Cigarette Smoking on Kidney Recently, it has become apparent that smoking cigarette is associated with excessive morbidity and mortality in various diseases prominently cardiovascular and lung diseases. Kidney is also an important target organ of smoking induced damage. There are numerous harmful substances found in tobacco and tobacco smoke. Nicotine is one of these substances that may be acquired through active and passive smoking[Halimi et al., 1998]. Cigarette smoking can cause acute and chronic effects [Grasse et al., 1994]. Acutely, cigarette smoking increases sympathetic nervous system activity resulting in tachycardia and high blood pressure. Increased sympathetic nervous system activity causes increased catecholamine activity in the circulation. Tis causes vasoconstriction in the vascular system [Ritz et al., 1998]. Vascular resistance in renovascular bed increases by 11% [Groppelli et al., 1992]. Tis reduces glomerular fltration rate by 15% and filtration fraction by 18%. Te chronic effects of cigarette smoking on kidney are less clear.

1.10 Chronic kidney disease and end stage renal disease

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Kidneys in all the vertebrates play a central role in overall homeostasis of the body. Main function of the kidney is to purify blood via glomerular filtration and excrete waste products in urine. Kidneys also play an eminent role in maintaining blood pressure, acid-base homeostasis, electrolyte balance and have a variety of endocrine functions, such as the production and secretion of erythropoietin for regulation of blood hemoglobin levels Many different direct or indirect insults can lead to chronic kidney disease (CKD), which over time may progress to end stage renal disease (ESRD). ESRD is the terminal stage of kidney disease. The common clinical signs of progression towards ESRD are a progressive decline in glomerular filtration and abnormal glomerular protein leakage[Hsu et al., 2009]. Proteinuria is not only a markerof renal damage but also a mediator of the progression of renal disease. In overtly proteinuric conditions, the non-physiological presence of proteinsactivates tubular epithelial cells. Activated tubular cells induce pro-fibrotic- and pro-inflammatory signaling and cells, which lead to tubulo-interstitial damage and progression of CKD[Burton et al., 1996).

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Chapter Two Materails and Methods

2-Materails and Methods 2.1 Subjects, Samples, Chemicals

2.1.1 Subjects:

A total of (85) healthy subjects were enrolled in the present study during their attendance to outpatient department at Rizgary hospital in Hawler city. Their ages were ranged from (27-56) years. Obese subjects (BMI> 29) and subjects who received medications were excluded. The subjects were classified according to the number of cigarettes smoked per day and the duration of smoking, into heavy smoker group (30 subjects), moderate smoker group (25 subjects), and non smoker group (control group)(30 subjects). 2.1.2. Sample collection Five milliliter of blood was withdrawn from each subject. The blood was allowed to clot in a plain tube for 20 minute at room temperature. The serum was separated by centrifugation at 3000 rpm for 10 minutes, then each subject serum was stored in three plain tubes (5 aliquots), frozen at -20 C until the day of biochemical assay (except for the enzyme studies which were done directly).

2.2- Methods

• 2.2.1- Determination of of Blood Urea • Serum (SUrea ) was determined using kit manufactured by RANDOX (United Kingdom).

Assay Principle • The series of reactions involved in the assay are as follows :• 1. Urea is hydrolyzed in the presence of water and urease to produce

ammonia and carbon dioxide.• Urease• Urea + H20 2NH3 + C02

• 2. In the presence of glutamate dehydrogenase (GLDH) and reduced nicotinamide adenine dinucleotide (NADH).the ammonia combines with a-ketoglutarate (a-KG) to produce L-glutamate.

•

• GLDH • 2NH4 + 2a-KG + 2 NADH 2 L-Glutamate + 2 NAD+ + H20 • The rate decrease in the NADH concentration is directly proportional to the

urea concentration in the specimen. It is determined by measuring the absorbance at 340 nm.

procedure

Procedure

pecimen Standard

1 ml 1 ml Working Reagent

----- 10 uJ Standard

10 uJ == Specimen

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Mix, and after 30 seconds read the absorbance A1 of the standard or specimen. Exactly 1 minute later, read the absorbance A2 of standard or specimen.

Calculation: Calculate the result as follows: • . 2.2.2- Determination of Serum Uric acid

• Serum (uric acid ) was determined using kit manufactured by RANDOX (United Kingdom).

•

• Principle of the method •

principle

•Uricase

•Uric acid + 2 H2O + O2 Allantoin + CO2 + H2O2

•POD

•H2O2 + 4-aminophenazone + phenol quinoneimine + 4 H2O

•Color intensity is directly proportional to [UA] in the specimen

Procedure

AssayStandardBlank

1mL1mL1mLWorking Reagent

25µLD.W

25µLStandard

25µLSerum

Mix well incubate for 5 minutes at 20-25 oC.Read absorbance at 520 nm

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Calculation•Ab.(Assay)

•Concentration of uric acid= ------------ *Standard solution

•(mg/dL)= Ab(standard)

•Stock Standard=10mg/100mL

•25µL for working •Wt(mg) V(mL)•--------- ---------•10 100ml•X 0.025mL X=0.0025mg/0.025mL

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Chapter Three Results and Discussion

3- Results and Discussion

The results of creatinine, urea, and uric acid in control and heavy smoker group were shown in Table (3-1). The results revealed that the level of creatinine , uric acid and urea in smoker were found significantly higher (p<0.001) than the control Table (3-1):. Comparison of Uric acid and Urea levels for heavy smoker group compared

with non smoker group

patameter Heavy smoker (n=30)

Non smoker (n=30) P –Value

Uric acid (mg/dL) 16.15±0.49

7.7±1.2 <0.0001

Urea (mg/dL) 20. 3 ± 0.62 11.91 ± 0.92 p<0.001

Serum creatinine

mg/dl

4.12 ± 1.12 0.81 ± 0.09 p<0.001

The results showed that serum Uric acid , Urea and creatinine levels were significantly high

(P value<0.0001) in heavy smoker group when compared with non smoker group, Table

1,Figure(1)

Figure(1): Comparison of Uric acid and Urea levels for heavy smoker group compared with non smoker group

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The results of creatinine, urea, and uric acid in control and Moderate smoker group were shown in Table (3-2). The results revealed that the level of creatinine , uric acid and urea in smoker were found non significantly higher (p >0.05) than the control Table (3-2):. Comparison of Serum Uric acid and Urea levels levels for moderate smoker

group compared with non smoker group

patameter Moderate smoker (n=30)

Non smoker (n=30) P –Value

Uric acid (mg/dL) 8.03±0.23 6.7±1.2 >0.05

Urea (mg/dL) 13.4± 0.52 11.91 ± 0.92 >0.05

Creatine(mg/dl) 1.12 ± 0.12 0.81 ± 0.09

Statistically non significant differences (P value>0.05) were observed in Uric acid , Urea and

creatinine levels for moderate smoker group comparing with non smoker group, Table 2.

Figure(2): Comparison of Uric acid and Urea, levels for moderate smoker group compared with non smoker group

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DISCUSSION

This study shows the effect of cigarette smoking on renal function, as indicated by serum creatinine, urea, and uric acid. It shows that there were an elevated values of serum creatinine, and urea in smoker people at (p<0.05) in comparison with the control subjects as shown in (Table 3-1),these findings are agreement with the results of other studies (El Sayed et al., 2013; Yuka et al., 2012). Moreover, these might be due to that the cigarette smoking increases renovascular resistance that lead to a significant fall in glomerular filtration rate (GFR), filtration fraction and renal plasma blood (Ritz et al., 1998). The decrease in GFR will lead to a decrease in distal tubular flow rate which leads to increase of urea reabsorption (JoAnn and Robert., 2011). plasma blood (. The decrease in GFR will lead to a decrease in distal tubular flow rate which leads to increase of urea reabsorption (JoAnn and Robert., 2011). Several mechanisms may be operative in inducing renal vasoconstriction and vascular damage. Nicotine increases plasma levels of vasoconstrictors including catecholamines, arginine, vasopressin and endothelin-1. Cigarette smoke damages endothelial cells, and nicotine induces smooth muscle cell proliferation (Pittilo et al., 1990). Other study attributed the renovascular resistance to activation of the sympathetic nervous system (Black et al., 1983). Previous study indicated that Lead (Pb) - linked glomerular dysfunction was observed in smokers possibly due to more recent exposure to high levels of Lead, as reflected by 30-50 percent higher serum cadmium (Cd) and Pb levels in smokers than nonsmokers. Smoking of 20 cigarettes per day results in inhalation of approximately 3.6 - 6.0 Lg of Cd, which is a cumulative nephrotoxicant (10). The nephrotoxicity of Cd results in changes in proximal tubular function, characterized by an increased excretion of beta 2-microglobulin and giving rise to the classical tubular proteinuria and in a glomerular dysfunction evidenced by an increased excretion of high molecular weight proteins and increased levels of beta 2-microglobulin and creatinine in plasma, and giving rise to a glomerular type proteinuria (Roszczenko et al., 2004). . In this study, level of uric acid in smokers is significantly lower than the nonsmoker group (P<0.05). This finding is in agreement with other studies that showed low serum uric acid in regular smokers and reduction of antioxidants including uric acid in smokers (Goraca and Skibska., 2005), this indicating the oxidative stress was increased in every cigarette smoked. Other studies, proved that even nonsmokers exposed to cigarette smoke have a significantly lower plasma antioxidant status than unexposed nonsmokers (Dietrich et al., 2003). In the mean time, the level of uric acid was raised in circulating antioxidant defenses and allows restoration of endothelium-dependent vasodilation (Goraca and Skibska., 2005). Therefore, high serum uric acid concentrations might be protective in situations characterized by increased cardiovascular risk and oxidative stress as smoking (Waring et al., 2006), however, the low level of serum uric acid induced more susceptibility to oxidative damage and accounts for the excessive free radical production (Reilly., 2013). Therefore, the possibility that uric acid confers protection against the development of atherosclerosis, in view of its antioxidant properties, has been recognized (Reilly., 2013). Moreover, other studies that proved that reduction of antioxidants including uric acid in

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smokers (Tomita et al., 2008) is due to both chronic exposures to cigarette smoke that is a significant source of oxidative stress and low intake of dietary antioxidants (Alberg., 2002). From these results we can suggest cigarettes substances can causes severe effects in PH in renal tubules and lead to change in glomerular filtration rate.

Conclusion

In this study an attempt has been made to detect the biochemical changes reflecting renal function during smokingThe kidney function is affected adversely in smoker group, indicated by the elevation of serum creatinine, urea, and a reduction of serum uric acid. The elevation of creatinine and urea almost attributed to significant fall in glomerular filtration rate (GFR), and a reduction of serum uric acid was attributed to reduce endogenous production as a result of exposure to cigarette smoke that is a significant source of oxidative stress.

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