Aminoguanidin ve Kardiyovasküler Sistem
Aminoguanidin AG , yüzyıldan uzun bir süredir bilinen, yapısal olarak L-Arjinin aminoasitine benzeyen, indüklenebilir nitrik oksit sentaz iNOS ’u selektif olarak inhibe eden, bu şekilde azalmış nitrik oksit NO oluşumuna neden olan bir bileşiktir. AG’nin önemli biyolojik etkileri geçtiğimiz yıllarda keşfedilmiştir. Keşfedilen ilk biyolojik etkisi, histamin, putreskin gibi aktif diaminlerin oksidatif deaminasyonunu katalizleyen, diamin oksidaz’ın inhibisyonudur. AG, etkili bir antioksidan ve serbest radikal süpürücüdür. AG hücre ve dokularda lipid peroksidasyonunun oluşumunu önler. Pek çok araştırmacı bu özellikleri üzerinden, AG’nin kardiyovasküler sistemdeki rolünü açıklamaya çalışmıştır. NO vasküler tonusun düzenlenmesi, endotel bütünlüğünün ve permeabilitesinin düzenlenmesi ve miyokard kontraktilitesinin düzenlenmesinde önemli bir rol oynar. Bu derlemede AG’nin kardiyovasküler sistem üzerindeki etkilerinin gözden geçirilmesi amaçlandı
Aminoguanidine and Cardiovascular System
Aminoguanidine AG is a compound which has been known for over a century, structurally similar to L-arginine amino acid, a selective inhibitor of inducible nitric oxide synthase iNOS and in this way leads to reduced nitric oxide NO . Its important biological effects were discovered in recent years. The first discovered effect is the inhibition of diamine oxidase which catalyzes the oxidative deamination of biologically active deamines such as histamine and putrescine. AG is an effective antioxidant and free radical scavenger. AG prevents the formation of lipid peroxidation in cells and tissues. By using these characteristics, many investigators tried to explain the role of AG on the cardiovascular system. NO plays a major role in the regulation of vascular tone, endothelial integrity and permeability regulation and myocardial contractility. In this review, we aimed to summarize the effects of AG on the cardiovascular system
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- 1. Budavari S, O’Neil MJ, Smith A, Heckelman PE.
In: Stecher PG. The Merck Index. 8th ed.
Rahway; Merck & Co Inc: 1989. p.56.
- 2. Nilsson BO. Biological effects of
aminoguanidine: an update. Inflamm Res 1999;
48(10): 509-15.
- 3. Ou P, Wolff SP. Aminoguanidine: a drug
proposed for prophylaxis in diabetes inhibits
catalase and generates hydrogen peroxide in vitro.
Biochem Pharmacol 1993; 46(7): 1139-44.
- 4. Baynes JW, Thorpe SR. Glycoxidation and
lipoxidation in atherogenesis. Free Radic Biol
Med 2000; 28(12): 1708-16.
- 5. Yoshida T, Iwakiri R, Noda T, Okamoto K,
Kojima M, Fukuyama K, et al. Histaminergic
effect on apoptosis of rat small intestinal mucosa
after ischemia reperfusion. Diges Dis Sci 2000;
45(6): 1138-44.
- 6. Özgüneş H, Atasayar S. Aminoguanidin ve
Hastalıklardaki Onemi. Turkiye Klinikleri J Med
Sci 2009; 29(4): 976-86.
- 7. Mansour M, Daba MH, Gado A, Al-Rikabi A, AlMajed A. Protective effect of L-arginine against
nephrotoxicity induced by cyclosporine in normal
rats. Pharmacol Res 2002; 45(6): 441-6.
- 8. Türker K, Kayaalp SO. Eikazonoidler ve Diğer
Otokoidler. Kayaalp SO, Ed. Rasyonel Tedavi Yönünden Tıbbi Farmakoloji. 9. Baskı. Ankara;
Hacettepe-Taş Kitapçılık Ltd Şti, 1998; 1513-48.
- 9. Lecour S, Maupoil V, Zeller M, Laubriet A, Briot
T, Rochette L. Levels of nitric oxide in the heart
after experimental myocardial ischemia. J
Cardiovasc Pharmacol 2001; 37: 55–63.
- 10. Moncado S. The L-arginine: Nitric oxide
pathway. Acta Physiology Scand 1992; 145(3):
201-27.
- 11. Nara K, Konno D, Uchida J, Kiuchi Y, Oguchi K.
Protective effect of nitric oxide against ironinduced neuronal damage. Journal of Neural
Transsmisssion 1999; 106: 835- 48.
- 12. Köse T. Deneysel diffüz beyin hasarında nitrik
oksit sentetaz inhibitörü aminoguanidin’ in
etkileri. Uzmanlık tezi, Isparta: 2006 (Bu tez
Süleyman Demirel Üniversitesi Araştırma Fonu
tarafından 1246-TU-06 proje numarası ile
desteklenmiştir).
- 13. Morris SM Jr, Billiar TR. New insights into the
regulation of inducible nitric oxide synthesis. Am
J Physiol 1994; 266(6 Pt 1): 829-39.
- 14. Polat A, Parlakpinar H, Tasdemir S, Colak C,
Vardi N, Ucar M, et al. Protective role of
aminoguanidine on gentamicin-induced acute
renal failure in rats. Acta histochemica 2006; 108:
365-71.
- 15. Yildiz G, Demiryurek AT, Sahin-Erdemli I,
Kanzik I. Comparison of antioxidant activities of
aminoguanidine, methyl-guanidine and guanidine
by luminolenhanced chemiluminescence. Br J
Pharmacol 1998; 124: 905–10.
- 16. Giardino I, Fard AK, Hatchell DL, Brownlee M.
Aminoguanidine inhibits reactive oxygen species
formation, lipid peroxidation, and oxidant-induced
apoptosis. Diabetes 1998; 47: 1114–49.
- 17. Babu E, Gopalakrishnan VK, Sriganth IN,
Gopalakrishnan R, Sakthisekaran D. Cisplatin
induced nephrotoxicity and the modulating effect
of glutathione ester. Mol Cell Biochem 1995; 144:
7–11.
- 18. Panagiotopoulos S, O'Brien RC, Bucala R,
Cooper ME, Jerums G. Aminoguanidine has an
anti-atherogenic effect in the cholesterolfed rabbit.
Atherosclerosis 1998; 136(1): 125-31.
- 19. Scaccini C, Chiesa G, Jialal I. A critical
assessment of the effects of aminoguanidine and
ascorbate on the oxidative modification of LDL:
evidence for interference with some assays of
lipoprotein oxidation by aminoguanidine. J Lipid
Res 1994; 35(6): 1085-92.
- 20. Jedidi I, Thérond P, Zarev S, Cosson C, Couturier
M, Massot C, et al. Paradoxical protective effect
of aminoguanidine toward low-density lipoprotein
oxidation: inhibition of apolipoprotein B
fragmentation without preventing its
carbonylation. Mechanism of action of
aminoguanidine. Biochemistry 2003; 42(38):
11356-65.
- 21. Parlakpinar H, Koc M, Polat A, et al. Protective
effect of aminoguanidine against nephrotoxicity
induced by amikacin in rats. Urol Res 2004; 32:
278–82.
- 22. Cigremis Y, Parlakpinar H, Polat A, et al.
Beneficial role of aminoguanidine on acute
cardiomyopathy related to doxorubicin-treatment.
Mol Cell Biochem. 2006; 285(1-2): 149-54.
- 23. Atalık KE, Doğan N. Nitrik oksit ve fizyolojik
etkileri. Genel Tıp Derg 1997; 7(3): 167-9.
- 24. Parlakpinar H, Ozer MK, Acet A. Effect of
aminoguanidine on ischemia-reperfusion induced
myocardial injury in rats. Molecular and Cellular
Biochemistry 2005; 277: 137–42.
- 25. Adams JA, Wu D, Bassuk J, et al. Nitric oxide
synthase isoform inhibition before whole body
ischemia reperfusion in pigs: vital or protective?
Resuscitation 2007; 74(3): 516-25.
- 26. Parlakpınar H, Örüm MH, Acet A. Kafeik asit
fenetil ester (KAFE) ve miyokardiyal iskemi
reperfüzyon (Mİ/R) hasarı. İnönü Üniversitesi
Sağlık Bilimleri Dergisi 2012; 1: 10-5.
- 27. Moro MA, Darley-Usmar VM, Goodwin DA, et
al. Paradoxical fate and biological action of
peroxynitrite on human platelets. Proc Natl Acad
Sci USA 1994; 91: 6702–6.
- 28. Woolfson RG, Patel VC, Neild GH, Yellon DM.
Inhibition of nitric oxide synthesis reduces infarct
size by an adenosine-dependent mechanism.
Circulation 1995; 91: 1545–51.
- 29. Depre C,Vanoverschelde JL, Goudemant JF,
Mottet I, Hue L. Protection against ischemic
injury by nonvasoactive concentrations of nitric
oxide synthase inhibitors in the perfused rabbit
heart. Circulation 1995; 92: 1911–8.
- 30. Bolli R, Patel BS, Jeroudi MO, Lai EK, McCay
PB. Demonstration of free radical generation in
‘stunned’ myocardium of intact dogs with the use
of the spin trap a-phenyl n-tert-butyl nitrone. J
Clin Invest 1988; 82: 476–85.
- 31. Garlick PB, Davies MJ, Hearse DJ, Slater TF.
Direct detection of free radicals in the reperfused
rat heart using electron spin resonance
spectroscopy. Circ Res 1987; 61: 757–60.
- 32. Aydogan H, Gürlek A, Parlakpinar H, Aydogan
N, Acet A. The Protective Effect of
Aminoguanidine on Random Pattern Skin Flap
Survival: An Experimental Study in Rats.
Turkiye Klinikleri J Med Sci 2007; 27: 36-43.
- 33. Rubbo H, Darley-Usmar V, Freeman BA. Nitric
oxide regulation of tissue free radical injury.
Chem Res Toxicol 1996; 9: 809–20.
- 34. Pryor W, Squadrito GL. The chemistry of
peroxynitrite: from the reaction of nitric oxide and
superoxide. Am J Physiol 1995; 268: 699–722.
- 35. Villa LM, Salas E, Darley-Usmar VM, Radomski
MW, Moncada S. Peroxynitrite induces both
vasodilation and impaired vascular relaxation in
the isolated perfused rat heart. Proc Natl Acad Sci
USA 1994; 91: 12383–7.
- 36. Wink DA, Hanbauer I, Krishna MC, DeGraff W,
Gamson J, Mitchell JB. Nitric oxide protects
against cellular damage and cytotoxicity from
reactive oxygen species. Proc Natl Acad Sci USA
1994; 90: 9813–7.
- 37. Yasmin W, Strynadka KD, Schulz R. Generation
of peroxynitrite contributes to ischemiareperfusion injury in isolated rat hearts.
Cardiovasc Res 1997; 33(2): 422–32.
- 38. Sahna E, Parlakpinar H, Cihan OF, Turkoz Y,
Acet A. Effects of aminoguanidine against renal
ischaemia–reperfusion injury in rats. Cell
Biochem Funct 2006; 24: 137–41.
- 39. Neely MD, Zimmerman L, Picklo MJ, Ou JJ,
Morales CR, Montine KS, et al. Congeners of N
(alpha)-acetyl-L-cysteine but not aminoguanidine
act as neuroprotectants from the lipid peroxidation
product 4-hydroxy-2- nonenal. Free Radic Biol
Med 2000; 29(10): 1028-36.
- 40. Chowdhury P, Soulsby ME, Scott JL. Effects of
Aminoguanidine on Tissue Oxidative Stress
Induced by Hindlimb Unloading in Rats. Ann Clin
Lab Sci 2009; 39 (1).
- 41. Moncada S, Palmer RM, Higgs EA. Nitric oxide:
Physiology, pathophysiology, and pharmacology.
Pharmacol Rev 1991; 43(2): 109–42.
- 42. Kayaalp SO. Rasyonel tedavi yönünden tıbbi
farmakoloji. Cilt 3. Ankara: Feryal Matbaası;
1990.
- 43. Busse R, Fleming I. Endothelial dysfunction in
atherosclerosis. J Vasc Res 1996; 33: 181-94.
- 44. Hasan K, Heesen BJ, Corbett JA, McDaniel ML,
Chang K, Allison W, et al. Inhibition of nitric
oxide formation by guanidines. Eur J Pharmacol
1993; 249(1): 101–16.
- 45. Nilsson BO, Kockum I, Rosengren E. Effects of
aminoguanidine and L-NAME on histamineinduced blood pressure drop in the rat. Acta
Physiol Scand 1997; 161(3): 339–44.