İsatinin İskemi ve Reperfüzyon Hasarı Üzerine Etkisi: İzole Kalpte Deneysel Bir Çalışma

Year 2019, Volume: 22 Issue: 1, 57 - 62, 11.04.2019

Zuhal Guksu Orkide Palabıyık Aziz Karaca Nejdet Süt Selma Arzu Vardar

Abstract

Giriş: İsatin, vücut sıvılarında endojen olarak bulunan, sinir sisteminde koruyucu, antikonvülzan ve sedatif
rolü olduğu bildirilen bir indoldür. Bu çalışmanın amacı, izole sıçan kalbinde oluşturulan iskemi reperfüzyon
modelinde isatinin sol ventrikül işlevi üzerine etkisini incelemektir.

Hastalar ve Yöntem: Erkek Wistar türü sıçanlar dört gruba ayrıldı. I ve I-atriyal natriüretik peptid (ANP)
gruplarına kalpler Langendoff düzeneğine yerleştirilmeden önce isatin [50 mg/kg intraperitoneal (ip)] verildi. C ve ANP gruplarına serum fizyolojik verildi. Tüm gruplara düşük akımlı iskemi uygulandı. İskeminin
15 dakika öncesinde, ANP ve I + ANP gruplarında perfüzyon solüsyonuna ANP (0.1 μM/L) eklendi. İskemi
öncesi ve sonrasında sol ventrikül gelişim basıncı (LVDP) ve maksimum ve minimum basınç değişimleri
kaydedildi. Tüm gruplarda perfüzyon sıvısından siklik guanozin monofosfate (cGMP) düzeyleri ölçüldü.

Bulgular: Reperfüzyonun 60. dakikasında I grubunun LVDP ve mimimum basınç değişim değerleri C grubuna benzer bulundu. İskemi öncesinde ve sonrasında, I grubunun cGMP değerleri C grubuna benzer ancak
ANP ve I + ANP gruplarından daha düşük bulundu.

Sonuç: İskemi öncesinde isatin verilmesi sıçan kalbinde kardiyak işlevi anlamlı şekilde değiştirmemektedir.
Bu çalışmanın bulguları, isatinin düşük akımlı iskemi sonrasında kardiyak işlevi bozucu etki oluşturmadığı
yönündedir.

Keywords

İsatin, atriyal natriüretik peptid, iskemi, cGMP

Effect of Isatin on Ischemia and Reperfusion Injury: an Experimental Study in the Isolated Rat Heart

Abstract

Introduction: Isatin is an endogen indole that is found in body fluids and reported as a neuroprotective,
anticonvulsant, and sedative agent. The aim of the present study was to investigate the effects of isatin on left
ventricle functions before and after low-flow ischemia in the isolated rat heart.

Patients and Methods: Male Wistar rats were divided into four groups. Isatin (I, 50 mg/kg intraperitoneally)
was administered in the I and I-atrial natriuretic peptide (ANP) groups 20 min before the hearts were placed on
the Langendorff apparatus. Serum physiologic was administered to the control (C) and ANP groups. Low-flow
ischemia was applied in all groups. ANP (0.1 μM/L) was added to perfusion solution in the ANP and I + ANP
groups 15 min before ischemia. Left ventricular developed pressure (LVDP) and maximum and minimum
pressure changes were recorded before and after ischemia. Cyclic guanosine monophosphate (cGMP) levels
were measured in the perfusate in all groups.

Results: LVDP and minimum pressure change values of the I group were found to be similar to the C group
at 60 min of reperfusion. The level of cGMP in the I group was similar to the C group but lower than the ANP
and I + ANP groups before and after ischemia.

Conclusion: The administration of isatin prior to cardiac ischemia does not significantly alter cardiac function
during the reperfusion period in rat heart. The results of the present study showed that isatin may not appear
to have a disturbing effect on cardiac functions after low-flow ischemia.

Keywords

Isatin, atrial natriuretic peptide, ischemia, cGMP

References

• 1. Buneeva OA, Kopylov AT, Tikhonova OV, Zgoda VG, Medvedev AE, Archakov AI. Effect of affinity sorbent on proteomic profiling of isatin-binding proteins of mouse brain. Biochemistry 2012;77:1326-38.
• 2. Gillam EM, Notley LM, Cai H, De Voss JJ, Guengerich FP. Oxidation of indole by cytochrome P450 enzymes. Biochemistry 2000;39:13817-24.
• 3. Mawatari K, Segawa M, Masatsuka R, Hanawa Y, Iinuma F, Watanabe M. Fluorimetric determination of isatin in human urine and serum by liquid chromatography postcolumn photoirradiation. Analyst 2001;126:33-6.
• 4. Igosheva N, Matta S, Glover V. Effect of acute stress and gender on isatin in rat tissues and serum. Physiol Behav 2004;80:665-8.
• 5. Igosheva N, Lorz C, O’Conner E, Glover V, Mehmet H. Isatin, an endogenous monoamine oxidase inhibitor, triggers a dose- and time-dependent switch from apoptosis to necrosis in human neuroblastoma cells. Neurochem Int 2005;47:216-24.
• 6. Medvedev A, Buneeya O, Gnedenko O, Ershov P, Ivanov A. Isatin, an endogenous nonpeptide biofactor: A review of its molecular targets, mechanisms of actions, and their biomedical implications. Biofactors 2018;44:95-108.
• 7. Pandeya SN, Smitha S, Jyoti M, Sridhar SK. Biological activities of isatin and its derivatives. Acta Pharm 2005;55:27-46.
• 8. Medvedev AE, Sandler M, Glover V. Interaction of isatin with type-A natriuretic peptide receptor: possible mechanism. Life Sci 1998;62:2391-8.
• 9. Hempel A, Friedrich M, Schlüter KD, Forssmann WG, Kuhn M, Piper HM. ANP protects against reoxygenation-induced hypercontracture in adult cardiomyocytes. Am J Physiol 1997;273:H244-H9.
• 10. Sangawa K, Nakanishi K, Ishino K, Inoue M, Kawada M, Sano S. Atrial natriuretic peptide protects against ischemia-reperfusion injury in the isolated rat heart. Ann Thorac Surg 2004;77:233-7.
• 11. Pataki I, Adamik A, Telegdy G. Isatin (Indole-2, 3-dione) inhibits natriuretic peptide-induced hyperthermia in rats. Peptides 2000;21:373-7.
• 12. Downey JM. Measuring infarct size by the tetrazolium method. 2003. Available from: https://www.southalabama.edu/ishr/help/help.htm
• 13. Brown DA, Lynch JM, Armstrong CJ, Caruso NM, Ehlers LB, Johnson MS, et al. Susceptibility of the heart to ischaemia-reperfusion injury and exercise-induced cardioprotection are sex-dependent in the rat. J Physiol 2005;564:619-30.
• 14. Yang XM, Philipp S, Downey JM, Cohen MV. Atrial natriuretic peptide administered just prior to reperfusion limits infarction in rabbit hearts. Basic Res Cardiol 2006;101;311-8.
• 15. Medvedev A, Sandler M, Glover V. The influence of isatin on guanylyl cyclase of rat heart membranes. Eur J Pharmacol 1999;384:239-41.
• 16. Vardar SA, Palabıyık O, Topuz TD, Gürel EE, Çalışkan S, Topçu Özen S, et al. Hemodynamic effects of atrial natriuretic peptide in ischemia-repertusion injury that occurs after exercise. Turk J Med Sci 2015;45:298-305.
• 17. Tourki B, Matéo P, Morand J, Elayeb M, Godin-Ribuot D, Marrakchi N, et al. Lebetin, a snake venom-derived natriuretic peptide, attenuates acute myocardial ischemic injury through the modulation of mitochondrial permeability transition pore at the time of reperfusion. Plos One 2016;11:1-22.