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620 клиничеСкаЯ лаБораторнаЯ диагноСтика original Paper INCReASeD SeRUM HOMOCYSteINe LeVeLS AND GLUtAtHIONe-S-tRANSFeRASe ACtIVItIeS IN ALCOHOLIC PAtIeNtS AtteNDING De-ADDICtION CeNtRe Sameer R Kulkarni – India, Mumbai-8, Byculla, Grant Medical College & Sir J.J. Group of Hospital, Department of Biochemistry, Senior Research Fellow, MS, Ph.D; K. Pratibha Ravindra – India, Mumbai- 400 098, Kalina, University of Mumbai, Department of Life Sciences, Post Doctorate Fellow, MS, Ph.D; Chitra Dhume – India, Goa 403 202, PO. Bambolim Complex, Goa Medical College, Department of Biochemistry, Associate Professor, MD, Ph.D; P.V. Rataboli – India, Goa 403 202, PO. Bambolim Complex, Goa Medical College, Department of Pharmacology, Assistant Professor, MD; Edmond Rodrigues – India, Goa 403 202, PO. Bambolim Complex, Goa Medical College, Department of Forensic Medicine, Associate Professor, MD; Edelweiss E. Rodrigues – India, Goa 403 202, PO. Bambolim Complex, Goa Medical College, Department of Physiology, Post Graduate Student, MBBS.

удК 616.89-008.441.13:577.152.:615.355]-07(540)(045)=111 Оригинальная статья ПовыШенный Уровень Сыворотки гомоциСтеина и дейСтвиЯ глУтатионаС-транСФераЗы У Пациентов С алкогольной ЗавиСимоСтью, ПоСещающиХ наркологичеСкий центр С.Р. Кулкарни – Индия, Мумбаи-8, Медицинский колледж, кафедра биохимии, старший научный сотрудник; К.П. Равиндра – Индия, Мумбаи 400 098, университет Мумбаи, кафедра наук о жизни, докторант; С. Дъюме – Индия, Гоа 403 202, Медицинский колледж Гоа, кафедра биохимии, адъюнкт-профессор; П.В. Ратаболи – Индия, Гоа 403 202, Медицинский колледж Гоа, кафедра фармакологии, доцент; Э. Родригез – Индия, Гоа 403 202, Медицинский колледж Гоа, кафедра судебной медицины, адъюнкт-профессор; Э.Е. Родригез – Индия, Гоа 403 202, Медицинский колледж Гоа, кафедра физиологии, аспирант.

дата поступления – 16.06.2010 г. дата принятия в печать – 16.09.2010 г.

Kulkarni S.R., Ravindra K.P., Dhume C., Rataboli P.V., Rodrigues E., Rodrigues E.E. increased serum homocysteine levels and glutathione-s-transferase activities in alcoholic patients attending de-addiction centre // saratov Journal of medical scientific Research. 2010. vol. 6, № 3. p. 620–624.

the purpose of this study was to investigate the effect of heavy alcohol consumption on serum Malondialdehyde, homocysteine status and glutathione-S –transferase (gSt) activities in alcoholics consuming illicit liquor from lower socioeconomic background attending deaddiction centre. the study was conducted in ninety alcoholic patients consuming illicit liquor from lower socio-economic background attending de-addiction centre and compared to healthy non alcoholic controls (n=90). Serum Malondialdehyde (MDa), serum homocysteine and activities of antioxidant enzyme glutathione-S – transferase (gSt) were estimated. alcoholics consuming illicit liquor attending de-addiction centre displayed significantly higher values of serum MDa concentration (p<0.001), serum homocysteine levels (p<0.001) and serum gSt activities (p<0.001) as compared to their non alcoholic healthy controls belonging to the same socioeconomic background. our results indicate that increase in serum Malondialdehyde (MDa) concentration marker of oxidative stress, serum homocysteine levels and serum glutathione-S-transferase (gSt) activities may enhance the susceptibility to vascular diseases in heavy illicit drinkers with poor nutritional status.

Key words: homocysteine, glutathione-S-transferase, alcohol.

Кулкарни С.Р., Равиндра К.П., Дъюме С., Ратаболи П.В., Родригез Э., Родригез Э.Е. Повышенный уровень сыворотки гомоцистеина и действия глутатиона-с-трансферазы у пациентов с алкогольной зависимостью, посещающих наркологический центр // Саратовский научно-медицинский журнал. 2010. Т. 6, № 3. С. 620–624.

Изучался эффект от интенсивного употребления алкоголя на сыворотку малондиалдегида, состояние гомоцистеина и активность глутатиона-с-трансферазы у алкоголиков из низкого социально-экономического слоя населения, употреблявших запрещенные (несертифицированные) спиртные напитки и посещавших наркологический центр.

В исследовании участвовали 90 пациентов с алкогольной зависимостью, употреблявших запрещенные спиртные напитки и посещавших наркологический центр, и контрольная группа – 90 лиц без алкогольной зависимости. были оценены сыворотка малондиалдегида, сыворотка гомоцистеина и активность антиоксидантфермента глутатиона-с-трансферазы.

у алкоголиков, употреблявших запрещенные спиртные напитки и посещавших наркологический центр, выявлен значительно более высокий показатель концентрации сыворотки малондиалдегида (p<0.001), уровня сыворотки гомоцистеина (p<0.001) и глутатиона-с-трансферазы (p<0.001) в сравнении с контрольной группой, принадлежащей к такому же социально-экономическому слою населения.

Результаты исследования показали, что с увеличением концентрации сыворотки малондиалдегида, сыворотки гомоцистеина и активности антиоксидант-фермента глутатиона-с-трансферазы может усиливаться восприимчивость к сосудистым заболеваниям при интенсивном употреблении запрещенных спиртных напитков и при недостаточном, неполноценном питании.

ключевые слова: гомоцистеин, глутатион-с-трансфераза, алкоголь.

introduction. alcoholic beverages have been used including negative effects on the cardiovascular system, and abused since the dawn of the history although most such as heart muscle disorders (i.e., cardiomyopathy), people who choose to drink can limit their intake to a heartbeat rhythm irregularities (i.e., arrhythmias), high level that produces no harm to their health or to society, blood pressure (i.e., hypertension), and strokes [1].

about 34 percent of the population drinks approximately Many epidemiologic studies have shown that alcohol 62 percent of all alcoholic beverages consumed. this consumption and the risk of cardiovascular disease are chronic heavy drinking is a significant factor in the deassociated in a J-shaped fashion [2, 3]. Moderate drinkvelopment of alcohol dependence, or alcoholism, and is ers of alcoholic beverages have a slightly reduced risk, associated with serious adverse health consequences, whereas heavy drinking is associated with an increased corresponding author: Sameer R kulkarni.

risk [4]. the concentration of total plasma homocysteine adress: 17: b-kaupineshwar, natu Paranjpee complex, (thcy) also was suggested as an explanatory factor [5, 6].

Mith bandar Road, thane (east) 400 608, Maharashtra, India.

email: srk_178@yahoo.co.in the concentration of thcy is a well-established indicator Саратовский научно-медицинский журнал. 2010. Том 6, № 3.

CLINICAL LABORAtORY DIAGNOStICS for the risk of cardiovascular disease [7, 8], and it seems centre. Serum Malondialdehyde (MDa) levels were meato be related to alcohol consumption [9]. the nature of this sured as thiobarbituric acid reacting substances (tbaRS), relation is, however, not fully clarified. Studies performed which serves as an index of extent of lipid peroxidation.

among alcoholics showed that a chronic intake of alcohol the activities of antioxidant enzyme like serum glutathileads to increased thcy concentrations [10]. one-S-transferase (gSt) and serum homocysteine levels homocysteine is sulphur containing amino acid were estimated. gSt is an enzyme involved in antioxidant formed during methionine metabolism [11]. It can di- defense mechanism which combats oxidative stress and merise to homocysteine, or form disulphide bonds with also involved in detoxication process. the present work is proteins to form so-called ‘protein-bound’ homocys- an attempt to determine the changes in oxidant – antioxiteine. homocysteine is a four-carbon amino acid [hS dant status and its contribution to the risk of cardiovascu(ch2)2chnh2cooh], resulting from the demethylation lar disease in alcoholism.

of methionine. homocysteine is a dimer composed of two methods. this study was carried out after getting oxidized molecules of homocysteine linked by a disulfide clearance from Institutional ethical Review committee, bond. Multiple forms of homocysteine circulate in blood:

grant Medical college & Sir J.J. groups of hospitals, the majority (65%) is disulfide linked to protein; ~30% byculla, Mumbai.

is in an oxidized state, mostly as disulfide links to itself In the present investigation, attempts were made to or cysteine; and ~1.5–4% is free reduced form. Storage design a discrimination procedure to separate alcoholof plasma or serum causes redistribution of these forms ics from controls and patients with non-alcoholic hepatic with an increase in the protein-bound fraction [12]. Indiseases using a combination of the most promising test.

crease in plasma concentration of homocysteine is comthe most powerful discrimination model was constructed mon in patients with stroke, peripheral vascular disease with the batteries of screening instruments for detecting [13], and coronary disease [14] and confer an indepenalcohol problems. cage [24], Michigan alcohol Screendent risk of atherosclerosis [15]. Measurement of total ing test (MaSt) [25], alcohol use Disorder Identification plasma or serum homocysteine represents the sum of test (auDIt) [26] and Severity of alcohol use Disorder oxidized and protein bound homocysteine. homocysData (SaDD) [27]. Patients between 25 and 45 years of teine contains a reactive sulfydryl group that can react age, willing to participate in the study and with no history with plasma constituents and this may promote oxidaof undergoing long term medical intervention for various tive damage. an elevated homocysteine level therefore reasons like cancer, Diabetes, advance alcohol liver disinduces thrombogenicity, causes procoagulant state and order, acute Respiratory Distress (aRD), chronic Renal promotes the proliferation of smooth muscle cells [16].

failure (cRf) and other cardio Vascular Disease (cVS) there appears to be increasing evidence that alcoserious medical, surgical, neurological conditions were hol toxicity may be associated with increased oxidative included in the study. also, patients with acute Psychotic stress and free radical associated injury [17]. oxidative state were excluded. alcoholic patients (n=90) attending damage induced by reactive oxygen species is caused the deaddiction center who met the following inclusion by increased production of Superoxide anions (o2-) and criteria’s and gave their informed consent were included its metabolites and/or by reduced bioavailability of antiin the study, these patients were matched for age, sex oxidant defense. alcohol is known to induce hyperlipidand socio economic status with normal controls (n=90) emia leading to enhanced lipid peroxidation [18]. lipid who were participating in a screening programme. these peroxidation mediated by free radicals is considered to controls were, to their knowledge healthy and had no be the major mechanism of cell membrane destruction reason to consult their local doctors during the preceding and cell damage. free radicals are formed in both physi12 months. further their nutritional anthropometry (age ological and pathological conditions in mammalian tisindependent anthropometric indices) was evaluated by sues [19]. the uncontrolled production of free radicals is the method of Rao`s [28].

considered as an important factor in the tissue damage exclusion criteria for patients and controls are:

induced by several pathophysiologies [20]. Moreover 1. Patients below 25 and above 45 are excluded from the body’s defense mechanisms would play a role in the study, patients undergoing long term medical interthe form of antioxidants and try to minimize the damvention for various reasons like cancer, Diabetes, adage, adapting itself to the above stressful situation. anvance alcohol liver disorder, aRD, cRf and other cVS tioxidants are compounds that dispose, scavenge, and serious medical, surgical, neurological conditions are suppress the formation of free radicals, or oppose their excluded from the study.

actions [21] and two main categories of antioxidants are 2. excessive smoking evaluated according to fagerthose whose role is to prevent the generation of free strom test for nicotine dependence with score more than radicals and those that intercept any free radicals that 15 are excluded [29]. Substance abuse such as cannaare generated [22]. they exist in both the aqueous and bis, nicotine, opium and other psychotropic substances membrane compartment of cells and can be enzymes or are excluded from the study.

non-enzymes.

3. Patients taking Vitamins and antioxidants or any Mammalian cells express a number of enzyme sysother significant supplements.

tems to detoxify RoS and their by-products, including 4. Immunocompramise and acute infectious state.

glutathione-S-transferase (gSt). gSt is a cytoplasmic class of large family of enzymes with their maximal activ- 5. Patients with acute Psychotic state or patients unwilling to participate in study.

ity seen in the hepatocytes. gSt’s are believed to exert a dietary survey of study population was conducted a critical role in cellular protection against RoS. within the hepatocytes, gSt’s are involved in conjugating re- by oral questionnaire method to assess per day consumption of calories, fats and protein. the daily food duced glutathione to electrophiles, hydroperoxides and xenobiotics derived from the metabolism of ethanol [23]. intake was recorded on a presented proforma and the In the present study, the following parameters were values were computed from standard chart of «Recomassessed in the serum to elucidate the oxidant antioxidant mended Dietary allowances for Indians» [30] and by estistatus in alcoholic patients consuming illicit liquor from mating dietary antioxidant vitamins in the blood of study low socio-economic background attending de-addiction population. further assessment of their Socio economSaratov Journal of Medical Scientific Research. 2010. Vol. 6, № 3.

622 клиничеСкаЯ лаБораторнаЯ диагноСтика ic status was done with the help of personal interview significant increase in the levels of serum MDa, serum based on per capita income and education [31]. homocysteine and serum gSt activities in alcoholic pawithin 24 hours of admission & overnight fasting tients compared to controls [p<0.001] (table 2).

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