Serum Uric Acid in Smokers
Bassam E. Hanna, Jamal M. Hamed, Luma M. Touhala
Objectives: To demonstrate the possible effect of smoking on serum uric acid.
Methods: Subjects enrolled in study were divided into two groups; nonsmokers and smokers, each with 60 male volunteers of the same social class and dietary habit without history of alcohol consumption, diabetes mellitus, hyperuricemia and gout, renal, joint, lung or heart diseases. Fasting blood and random urine samples were obtained from both groups for measurement of uric acid and creatinine. Calculation of both urine uric acid/urine creatinine ratio and fraction excretion of uric acid were done. The results were statistically evaluated by standard statistical methods.
Results: No significant differences in the age, serum creatinine, spot urine uric acid/urine creatinine ratio and fraction excretion of uric acid between the two groups, serum uric acid was significantly lower in smokers. In smokers there was significant negative correlation of smoking status (average number of cigarette smoked/day, duration of smoking and cumulative amount of smoking) with serum uric acid.
Conclusion: After exclusion of other factors affecting uric acid level, the significant low serum uric acid level in smokers was attributed to reduce endogenous production as a result of chronic exposure to cigarette smoke that is a significant source of oxidative stress. As this reduction is proportionate with smoking status and predisposes to cardiovascular disease, it is, therefore, recommended for smokers to stop or reduce smoking and introduce serum uric acid estimation as routine test since its cheap and simple to reflect their antioxidant level.
Keywords: Smokers; Uric acid; CVD.
Submitted: 25 July 2008
Reviewed: 12 Aug 2008
Accepted: 19 Sept 2008
From the Department of Medicine, Nineveh college of medicine Biochemistry, Mosul, IRAQ
Address Corresponding and reprint request to: Dr. Bassam E. Hanna, Department of Medicine, Nineveh college of medicine Biochemistry, Mosul, IRAQ
Cigarette-smoking is a well-known risk factor for atherosclerosis development and its complications including cerebral and cardiovascular diseases(CVD)1,2 through vascular endothelial damage3 that possibly occurs through oxygen free radicals production as superoxide radicals, hydrogen peroxide and hydroxyl radicals.4,5 Several enzymes capable of producing oxygen free radicals including xanthine oxidase, NADPH oxidase, myeloperoxidase, and endotoxin.4,5
As cigarette smoke contains superoxide and reactive nitrogen species that readily react with various biomolecules,1,6-9 it has been hypothesized that some of the adverse effects of smoking may result from oxidative damage to endothelial cells, which results in nitric oxide (NO) shortage.1,10,11 (NO) shortage regulates vascular tone that accelerates insufficiency of coronary artery and vasoconstriction in many different tissues.3,12 Therefore imbalance between oxidants and antioxidants may play an important role in the susceptible smoker.13,14 In addition cigarette smokers have increased inflammatory responses that further enhance their oxidative stress.8,9
Since in humans, uric acid is the most abundant aqueous antioxidant, accounting for up to 60% of serum free radical scavenging capacity15 and is an important intracellular free radical scavenger during metabolic stress including smoking,16,17 therefore , measurement of its serum level reflects the antioxidant capacity.15
The aim of this study is to demonstrate the possible effect of smoking on serum uric acid concentration.
The study was conducted during the period from March to June 2008, the subjects enrolled in this study were divided into two groups (group I and group II).
Group I, considered as a control group, was composed of 60 apparently healthy nonsmoker male volunteers, their ages ranged from 20 to 69 years.
Group II, considered as a smoker group composed of 60 cigarette-smoker male volunteers, their ages ranged from 16 to 71 years.
A complete record of history was obtained, including name, age, average number of daily cigarettes smoked daily, duration of smoking, dietary habit, alcohol consumption , social class, past medical and drug history.
Members of both groups were within the same social class and dietary habit with no history of alcohol consumption, diabetes mellitus, hyperuricemia and gout, renal, joint, lung or heart diseases.
Fasting blood and random urine samples were obtained from both groups for colorimetric measurement of uric acid and creatinine that were done by Jaffe’s reaction kinetic method18 using a kit supplied by Biolabo Company and by uricase method18 using a kit supplied by Biomeriux Company respectively by obtaining absorbencies using Cecil spectrophotometer-CE 1011 at the Biochemistry Laboratory of Nineveh College of Medicine in Mosul, Iraq.
From the data of serum and urine uric acid and creatinine the calculation of both urine uric acid/urine creatinine (Uuric acid/Ucreatinine) ratio19 and fraction excretion of uric acid (FEuric acid)19,20 were done in both groups, calculation of FEuric acid was done by the following formula(19,20):
FEuric acid = (Uuric acid*Screatinine/Suric acid* Ucreatinine)*100
The results were statistically evaluated by standard statistical methods including mean, standard deviation (SD) range
No statistical significant differences were noted in the age, serum creatinine, spot Uuric acid/Ucreatinine ratio and FEuric acid between two groups (P>0.05, Table I), whereas serum uric acid was significantly lower in group II than group I (P<0.001, Table 1, Fig.1).
The coefficient of variations of serum uric acid and creatinine were 17.68 and 18.46 in group I and 32.14 and 32.46 in group II respectively.
Table 2 demonstrates the mean ± SD and the range of smoking status in group II including the average number of cigarettes smoked/day, duration of smoking and cumulative amount of smoking (calculated by multiplying the number of cigarettes smoked/day with the duration of smoking).
In group II, a statistical significant negative correlations were noted between smoking status parameters and serum uric acid (P<0.001, Fig. 2, Fig. 3, Fig. 4), no such correlations with serum creatinine (P>0.050).
Table 1: Comparison between parameters of both groups; Values are presented as mean ± SD
able 1: Comparison between parameters of both groups; Values are presented as mean ± SD
Table 2: Smoking status in group II; Values are presented as mean ± SD
Figure 1: Spread of uric acid levels in group I and group II
Figure 2: Correlation between serum uric acid and number of cigarette smoked/day in group II
Figure 3. Correlation between serum uric acid and duration of smoking in group II
Figure 4. Correlation between serum uric acid and cumulative amount of smoking in group II
Many but not all epidemiological studies have suggested that high serum uric acid is a risk factor for CVD24-28 and warranted to evaluate its prognostic implications and potential utility in the monitoring of therapy.29 This raised level of serum uric acid parallel to an increased risk of CVD could be either primary or secondary to underlying causes of CVD.30-35 However, the specific role of serum uric acid in this constellation remains uncertain36 although may be involved in platelet adhesiveness, aggregation or inflammation37-39 and may be implicated in the genesis of hypertension.40
In contrast , there is some evidence suggesting that the increase of serum uric acid is protective against CVD since uric acid acts as an endogenous antioxidant41-43 and the higher serum uric acid levels found in CVD patients suggests that any protective antioxidant effect which uric acid has is overwhelmed by other negative effects on pathogenesis.44 Recently the viability of administering uric acid in solution has been established41even they do not specifically address the question of a biological link between uric acid and mechanisms of endothelial dysfunction or atherosclerosis since inhibition of xanthine oxidase by allopurinol is likely to reduce the production of hydrogen peroxide and thereby ameliorate oxidative stress even in smokers45 independent of its effects on uric acid.46 Furthermore, allopurinol has antioxidant properties.47 Therefore, raising serum uric acid concentrations protects against acute oxidative damage as in smoking.48
In this study, although serum uric acid level in smokers did not reach the lower reference range (0.12 mmol/L)49 however it is significantly lower than the nonsmoker group (P<0.001) and has significant negative correlation with smoking status including the average number of cigarettes smoked/day, duration of smoking and cumulative amount of smoking. This finding is in agreement with other studies that showed low serum uric acid in regular smokers1,50 and reduction of antioxidants including uric acid in smokers51,52 indicating that oxidative stress increases everytime a cigarette is smoked.1 Other studies proved that even nonsmokers exposed to cigarette smoke have a significantly lower plasma antioxidant status than unexposed nonsmokers do, independent of differences in dietary antioxidant intakes.51 It even proved that administration of uric acid raises circulating antioxidant defenses and allows restoration of endothelium-dependent vasodilation.11,52 Therefore, high serum uric acid concentrations might be protective in situations characterized by increased cardiovascular risk and oxidative stress as smoking,11 and by reducing its level it increases susceptibility to oxidative damage and accounts for the excessive free radical production.53 Therefore, the possibility that uric acid confers protection against the development of atherosclerosis, in view of its antioxidant properties, has been recognized.54,55
In this study, serum creatinine, FEuric acid and Uuric acid/Ucreatinine ratio are not significantly differ between two groups, in addition to that FEuric acid and Uuric acid/Ucreatinine ratio values lie within the mean ± SD observed in the control group by other studies.19,56-58 Since these tests have been reported to be useful to evaluate renal handling of uric acid59-63 and as serum uric acid concentrations are highly dependent on endogenous production as well as renal excretion.64,65 Therefore, low serum uric acid level in smokers is attributed to reduction of endogenous production. As result of smoking, oxidative stress consumption rather than increased renal excretion after exclusion of other factors that affect its level as all members of groups I and II are subjected to the same preanalytical and postanalytical factors and all of them are within the same social class, dietary habit with no history of alcohol consumption in addition to standardization of laboratory uric acid measurement to avoid analytical variations.
This finding is in agreement with other studies that proved that reduction of antioxidants including uric acid in smokers66 is due to both chronic exposure to cigarette smoke that is a significant source of oxidative stress8,53 and low intake of dietary antioxidants.67
After exclusion of other factors affecting uric acid level, the significant low serum uric acid level in smokers was attributed to reduce endogenous production as a result of chronic exposure to cigarette smoke that is a significant source of oxidative stress. As this reduction is proportionate with smoking status and predisposes to cardiovascular disease, it is recommended for smokers to stop or reduce smoking and introduce serum uric acid estimation as routine test since its cheap and simple to reflect their antioxidant level.