Günfer Turgut, Simin Rota, Hülya Aybek, Sebahat Turgut, Seelahattin Sert, Osman Genç

The effects of adenosine on plasma homocysteine levels and some other biochemical parameters

Süleyman Demirel Üniversitesi TIP FAKÜLTESİ DERGİSİ: 2007 Aralık; 14(4) The effects of adenosine on plasma homocysteine levels and some other biochemical parameters Günfer Turgut*, Simin Rota**, Hülya Aybek**, Sebahat Turgut*, Selahattin Sert**, Osman Genç* *Pamukkale University Faculty of Medicine Departments of Physiology, Denizli, Turkey **Pamukkale University,Faculty of Medicine, Departments of Biochemistry Denizli, Turkey Özet Adenozinin Plazma Homosistein ve Bazı Biyokimyasal Parametreler Üzerine Etkileri. Adenozin kardiyovasküler hastalıkların fizyolojisi ve gelişiminde önemli bir role sahiptir. Bazı klinik ve epidemiyolojik çalışmalar ateroskleroz gelişiminde yüksek plazma homosistein düzeylerinin önemini ortaya koymuştur. Yüksek plazma homosistein düzeylerinin koroner, kardiyovasküler ve periferik damar hastalıklarında bağımsız bir risk faktörü olduğu da gösterilmiştir. Bu çalışmada, ekzojen olarak adenozin verilmesinin plazma homosistein düzeylerine ve bazı biyokimyasal parametreler üzerine olan etkisi araştırıldı. 20 yetişkin Balb-c cinsi sıçan çalışmaya dahil edildi. Deney grubuna (n=10) 0,2 ml intraperitoneal yolla 3 gün (2 kez/gün) 30 mg/kg adenozin verildi. Kontrol grubuna (n=10) ise 0.2 ml 0.09% NaCl aynı yolla uygulandı. Eter anestezisi altında intrakardiyak yoldan alınan kan örnekleri heparinli tüplere konuldu. Plazma homosistein, total kolesterol, HDL-kolesterol, trigliserid, C-reactif protein, alkalen fosfataz, aspartat amino transferaz, alanin amino transferaz, gama-glutamil transferaz düzeyleri ölçüldü. LDL-kolesterol and VLDL- kolesterol düzeyleri uygun formüllerle hesaplandı. Gruplar arasındaki farklılıklar Mann-Whitney U testi ile analiz edildi. Gruplar arasında plazma homosistein ve diğer biyokimyasal parametrelerde anlamlı farklılık bulunamadı. Bu sonuçlar, eksojen olarak adenozin uygulanmasının plazma homosistein, total kolesterol, HDL-kolesterol, trigliserid, C-reactif protein, alkalen fosfataz, aspartat amino transferaz, alanin amino transferaz, gama-glutamil transferaz, LDL-kolesterol ve VLDL-kolesterol düzeylerini etkilemediğini göstermektedir. Anahtar kelimeler: Adenozin, homosistein, fare, biyokimyasal parametreler Abstract The effects of adenosine on plasma homocysteine levels and some other biochemical parameters Adenosine has an important role in (physiology and pathological cardiovascular aspects) the pathogenesis of cardiovascular diseases. Some clinical and epidemiological studies revealed the importance of high plasma homocysteine levels in the progression of atherosclerosis. It was also shown that high level of plasma homocysteine is an independent risk factor for coronary, cerebrovascular and peripheral occlusive vascular diseases. In this study we investigated the effects of exogenous adenosine administration on plasma homocysteine levels and some other biochemical parameters. Twenty adult male Balb-c mice were included to the study. To the experimental group (n=10) intraperitoneal 0.2 ml, 30 mg/kg adenosine was applied twice in a day for three consecutive days. To the control group (n=10) intraperitoneal 0.2 ml 0.09% NaCl was applied twice in a day for 3 consecutive days. After blood was collected into heparinized tubes under the ether anaesthetized mice by intracardiac puncture. Plasma homocysteine, total cholesterol, HDL-cholesterol, triglyceride, C-reactive protein, alkaline phosphatase, aspartat amino transferase, alanin amino transferase, gama-glutamyl transferase were measured. LDL-cholesterol and VLDL-cholesterol levels were calculated by using appropriate formulas. Differences between the groups were analysed by Mann-Whitney U test. There was no difference in plasma homocysteine and other biochemical parameters between both groups. These results show that exogenous adenosine application did not effect the plasma homocysteine, total cholesterol, HDL-cholesterol, triglyceride, C-reactive protein, alkaline phosphatase, aspartat amino transferase, alanin amino transferase, gama-glutamyl transferase, LDL-cholesterol and VLDL-cholesterol levels. Key Words: Adenosine, homocysteine, mice, biochemical parameters

Anahtar Kelimeler:

Adenozin, homosistein, fare, biyokimyasal parametreler

PDF

___

Osswald H, Muhlbauer B, Vallon V. Adenosine and
tubuloglomerular feedback. Blood Purif 1997;15:24352.
Downey JM, Liu GS, Thornton JD. Adenosine and the anti-infarct effects of preconditioning. Cardiovasc Res 1993;27: 38.
Ely S, Berne R. Protective effects of adenosine in myocardial ischemia. Circulation 1992;85:893904.
Ubbink JB, Vermaak WJ, Van Der Merwe A, Becker PJ. The effect of blood sample aging and food consumption on plasma total homocysteine levels. Clin Chim Acta 1992;207: 11928.
Ueland PM, Refsum H, Brattstrom L. Plasma homocysteine and cardiovascular disease, Francis DB (Eds), Marcel Dekker, 1992, pp 183236.
Temple ME, Luzier AB, Kazierad DJ. Homocysteine as a risk factor for atherosclerosis. Ann Pharmacother 2000;34:5765.
Boger RH, Sydow K, Borlak J, Thum T, Lenzen H, Schubert B et al. LDL cholesterol upregulates synthesis of asymmetrical dimethylarginine in human endothelial cells: involvement of S-adenosylmethionine-dependent methyltransferases. Circ Res 2000;87:99105.
Dayal S, Bottiglieri T, Arning E, Maeda N, Malinow MR, Sigmund CD et al. Endothelial dysfunction and elevation of S-adenosylhomocysteine in cystathionine b-synthase-deficient mice. Circ Res 2001;88: 12039.
Majors A, Ehrhart LA, Pezacka EH. Homocysteine as a risk factor for vascular disease. Enhanced collagen production and accumulation by smooth muscle cells. Arterioscler Thromb Vasc Biol 1997;17:207481.
Pruefer D, Scalia R, Lefer AM. Homocysteine provokes leukocyteendothelium interaction by downregulation of nitric oxide. Gen Pharmacol 1999;33:48798.
Matthias D, Becker CH, Riezler R, Kindling P. Homocysteine induced arteriosclerosis-like alterations of the aorta in normotensive and hypertensive rats following application of high doses of methionine. Atherosclerosis 1996;122:20116.
Brattström L, Wilcken D. Homocysteine and cardiovascular disease: cause or effect? Am J Clin Nutr 2000;72:31523.
Chen YF, Li PL, Zou AP. Effect of hyperhomocysteinemia on plasma or tissue adenosine levels and renal function. Circulation 2002;106:127581.
Sciotti VM, Van Wylen DG. Attenuation of ischemia- induced extracellular adenosine accumulation by homocysteine. J Cereb Blood Flow Metab 1993;13:20813.
Schrader J, Schutz W, Bardenheuer H. Role of S- adenosylhomocysteine hydrolae in adenosine metabolism in mammalian heart. Biochem J 1981;196:6570.
Biaggioni I, Mosqueda-Garcia R. Adenosine in cardiovascular homeostasis and the pharmacologic control of its activity. In Hypertension, Pathophysiology, Diagnosis, and Management. Laragh JH, Brenner BM (eds), 2nd ed., Raven, 1995, pp 112540.
Ethier MF, Chander V, Dobson JG. Adenosine stimulates proliferation of human endothelial cells in culture. Am J Physiol 1993;265:1318.
Mccully KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol 1969;56:11128.
Vollset SE, Refsum H, Tverdal A, Nygard O, Nordrehaug JE, Tell GS. Plasma total homocysteine and cardiovascular and noncardiovascular mortality: the Hordaland Homocysteine Study. Am J Clin Nutr 2001;74:1306.
Durand P, Lussier-Cacan S, Blache D. Acute methionine load-induced hyperhomocysteinemia enhances platelet aggregation, thromboxane biosynthesis, and macrophage-derived tissue factor activity in rats. FASEB J 1997;11:115768.
Lenz SR, Sobet CG, Piegors DJ, Bhopaktar MY, Faraci FM, Manilow MR. Vascular dysfunction in monkeys with diet-induced hyperhomocysteinemia. J Clin Invest 1996;98:249.
Engler R. Adenosine: The signal of life? Circulation 1991;84:9514.
Belardinelli L, Linden J, Berne RM. The cardiac effects of adenosine. Prog Cardiovasc Dis 1989;32:7397.
Mubagwa K, Flameng W. Adenosine, adenosine receptors and myocardial protection: an updated overview. Cardiovasc Res 2001;52:2539.
Deussen A. Adenosinethe missing link to understanding homocysteine pathogenicity or more smoke on the horizon? Cardiovasc Res 2003;59:25961.
Fredholm BB, Ijzerman AP, Jacobson KA, Klotz KN, Linden J. International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev 2001; 53:52752.
Riksen NP, Rongen GA, Blom HJ, Russel FGM, Boers GHJ, Smits P. Potential role for adenosine in the pathogenesis of the vascular complications of hyperhomocysteinemia. Cardiovascular Research 2003;56:2716.
Thornton JD, Liu GS, Olsson RA, Downey JM. Intravenous pretreatment with A1-selective adenosine analogues protects the heart against infarction. Circulation 1992;85:65965.
Van Belle H. Nucleoside transport inhibition: a therapeutic approach to cardioprotection via adenosine? Cardiovasc Res 1993;27:6876.
Dubey RK, Gillespie DG, Jackson EK. A(2B) adenosine receptors stimulate growth of porcine and rat arterial endothelial cells. Hypertension 2002;39:5305.
Ueland PM. Pharmacological and biochemical aspects of S-adenosylhomocysteine and S- adenosylhomocysteine hydrolase. Pharmacol Rev 1982;34:22353.
Hultberg B, Andersson A, Isaksson A. Hypomethylation as a cause of homocysteine-induced cell damage in human cell lines. Toxicology 2000;147:6975.
Deussen A, Borst M, Schrader J. Formation of S- adenosylhomocysteine in the heart. I: An index of free intracellular adenosine. Circ. Res 1988;63:2409.
Liu S, Wnuk SF, Yuan C, Robins MJ, Borchardt RT. Adenosine-5'-carboxaldehyde: a potent inhibitor of S- adenosyl-L-homocysteine hydrolase. J Med Chem 1993;36:8837.
Mehdi S, Jarvi ET, Koehl JR, McCarthy JR, Bey P. The mechanism of inhibition of S-adenosyl-L- homocysteine hydrolase by fluorine-containing adenosine analogs. J Enzyme Inhib 1990;4:113.