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SIÇANLARDA DOKSORUBISIN KAYNAKLI KARDİYOTOKSİSİTE ÜZERINE CB1 RESEPTÖR LİGANDI HEMOPRESSİNİN KARDİYOPROTEKTİF ETKİSİ: SİNTİGRAFİK, ELEKTROKARDİYOGRAFİK VE BİYOKİMYASAL BİR ÇALIŞMA

CARDIOPROTECTIVE EFFECT OF THE CB1 RECEPTOR LIGAND HEMOPRESSIN ON DOXORUBICIN-INDUCED CARDIOTOXICITY IN RATS: A SCINTIGRAPHIC, ELECTROCARDIOGRAPHIC, AND BIOCHEMICAL STUDY

Reyhan Koroglu(SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, İSTANBUL SULTAN ABDÜLHAMİD HAN SAĞLIK UYGULAMA VE ARAŞTIRMA MERKEZİ, DAHİLİ TIP BİLİMLERİ BÖLÜMÜ, NÜKLEER TIP ANABİLİM DALI)0000-0002-3344-915X
Hatice Aygün(BIRUNI UNIVERSITY, BİRUNİ RESEARCH CENTER)0000-0002-4272-0562
Sayfa
556–564
Yayın Tarihi
2026-10-12
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⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

BULGULAR: Sıçanlarda DOX'un neden olduğu kardiyotoksisite; uzamış QRS kompleksi ve QT aralığı, ST segment elevasyonu gibi EKG anormallikleri, azalmış kalp hızı, artmış kardiyak troponin T (cTnT) düzeyleri, yükselmiş tümör nekroz faktörü-alfa (TNF-α) ve interlökin-6 (IL-6) konsantrasyonları ile artmış 99mTc-PYP tutulumu ile karakterizedir (p < 0,001).

📌 3 Maddede Bu Makale

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Amaç & Hipotez:AMAÇ: Doksorubisin (DOX), kemoterapide yaygın olarak kullanılan bir antineoplastik ilaçtır.
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Temel Bulgular & Veri:Bu çalışmada, hemopressinin DOX ile indüklenen kardiyotoksik sıçanlar üzerindeki etkilerini sintigrafik, elektrokardiyografik (EKG) ve biyokimyasal yöntemlerle değerlendirmek amaçlanmıştır.
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Sonuç & Katkı:BULGULAR: Sıçanlarda DOX'un neden olduğu kardiyotoksisite; uzamış QRS kompleksi ve QT aralığı, ST segment elevasyonu gibi EKG anormallikleri, azalmış kalp hızı, artmış kardiyak troponin T (cTnT) düzeyleri, yükselmiş tümör nekroz faktörü-alfa (TNF-α) ve interlökin-6 (IL-6) konsantrasyonları ile artmış 99mTc-PYP tutulumu ile karakterizedir (p < 0,001).
🔬Tür:Deneysel Tarla Denemesi
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:Hemopressin · Doksorubisin · Kardiyotoksisite

Özet

AMAÇ: Doksorubisin (DOX), kemoterapide yaygın olarak kullanılan bir antineoplastik ilaçtır. Doksorubisinin kardiyotoksisitesi, yüksek morbidite ve mortalite ile seyreden bir toksisite olarak sıklıkla görülür. Bu çalışmada, hemopressinin DOX ile indüklenen kardiyotoksik sıçanlar üzerindeki etkilerini sintigrafik, elektrokardiyografik (EKG) ve biyokimyasal yöntemlerle değerlendirmek amaçlanmıştır. GEREÇ VE YÖNTEM: Yirmi sekiz erkek Wistar sıçan rastgele dört gruba ayrıldı: kontrol (CON), doksorubisin (DOX), HEM 10 μg/kg ve HEM 50 μg/kg. Kardiyotoksisite, DOX'un üç ardışık gün boyunca (12., 13. ve 14. günler) intraperitoneal (i.p.) uygulanmasıyla oluşturuldu (toplam kümülatif doz: 18 mg/kg). HEM gruplarına 14 gün boyunca günlük 10 veya 50 μg/kg HEM (i.p.) uygulanırken, 12.–14. günlerde eş zamanlı olarak DOX (toplam kümülatif doz: 18 mg/kg, i.p.) verildi. On beşinci günde, HEM'in DOX kaynaklı kardiyotoksisite üzerindeki etkileri sintigrafik, elektrokardiyografik (EKG) ve biyokimyasal yöntemlerle değerlendirildi. BULGULAR: Sıçanlarda DOX'un neden olduğu kardiyotoksisite; uzamış QRS kompleksi ve QT aralığı, ST segment elevasyonu gibi EKG anormallikleri, azalmış kalp hızı, artmış kardiyak troponin T (cTnT) düzeyleri, yükselmiş tümör nekroz faktörü-alfa (TNF-α) ve interlökin-6 (IL-6) konsantrasyonları ile artmış 99mTc-PYP tutulumu ile karakterizedir (p < 0,001). HEM 10 μg/kg ve HEM 50 μg/kg ile ön tedavi, DOX'un neden olduğu EKG değişikliklerini önemli ölçüde bastırmıştır (p<0,001). Dahası, HEM ile ön tedavi, sıçanlarda serum cTnT düzeyini, kalp dokusu TNF-α, IL-6 ve 99mTc-PYP alımını önemli ölçüde azaltmıştır (p < 0,001). SONUÇ: EKG anormallikleri, biyokimyasal değişiklikler ve 99mTc-PYP alımı parametreleri, sıçanlarda DOX kaynaklı kardiyotoksisiteyi gösterebilir. Bu çalışmanın sonuçlarına göre, HEM'in DOX kaynaklı kardiyotoksisite üzerinde güçlü yararlı etkileri vardır.

Abstract

OBJECTIVE: Doxorubicin (DOX) is a prominent chemotherapeutic agent. However, its use is limited by serious cardiotoxicity. This study investigates the cardioprotective potential of hemopressin against DOX-induced cardiac injury in rats through scintigraphic, ECG, and biochemical evaluations. MATERIAL AND METHODS: Twenty-eight male Wistar rats were divided into four groups: control (CON), doxorubicin (DOX), HEM 10 μg/kg, and HEM 50 μg/kg. Cardiotoxicity was induced by intraperitoneal administration of DOX over three consecutive days (days 12–14), with a total cumulative dose of 18 mg/kg. Rats in the HEM groups received daily intraperitoneal HEM (10 or 50 μg/kg) for 14 days, with concomitant DOX administration on days 12–14. On day 15, cardiac injury was evaluated using scintigraphic imaging, electrocardiographic recordings, and biochemical analyses. RESULTS: DOX-induced cardiotoxicity in rats was characterized by ECG abnormalities, including prolonged QRS complex and QT interval, ST-segment elevation, reduced heart rate, increased cardiac troponin T (cTnT) levels, elevated tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) concentrations, and increased 99mTc-PYP uptake (p < 0.001). Pretreatment with HEM 10 μg/kg and HEM 50 μg/kg significantly suppressed DOX-induced ECG changes (p<0.001). Moreover, pretreatment with HEM significantly reduced serum cTnT levels, heart tissue TNF-α and IL-6 concentrations, and 99mTc-PYP uptake in rats (p < 0.001). CONCLUSIONS: Electrocardiographic alterations, biochemical deviations, and increased myocardial uptake of 99mTc-PYP are indicative of DOX-induced cardiotoxicity in rats. Findings from this study demonstrate that HEM exerts significant cardioprotective effects against DOX-associated cardiac injury.

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Bu Makaleye Atıf Yap

Koroglu, R., Aygün, H. (2026). SIÇANLARDA DOKSORUBISIN KAYNAKLI KARDİYOTOKSİSİTE ÜZERINE CB1 RESEPTÖR LİGANDI HEMOPRESSİNİN KARDİYOPROTEKTİF ETKİSİ: SİNTİGRAFİK, ELEKTROKARDİYOGRAFİK VE BİYOKİMYASAL BİR ÇALIŞMA. Kocatepe Tıp Dergisi, Cilt: 27 Sayı: 4, 556–564. https://doi.org/10.18229/kocatepetip.1732052

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Kaynakça (51)

  1. Young RC, Ozols RF, Myers CE. The anthracycline antineoplastic drugs. N Engl J Med. 1981;305:139–53.
  2. Lefrak EA, Pitha J, Rosenheim S, Gottlieb JA. A clinicopathologic analysis of adriamycin cardiotoxicity. Cancer. 1973;32:302–14.
  3. Wu M, Yang Y, Cao M, et al. Drug-Induced Cardiotoxicity in Children During the Past 30 Years: A Bibliometric Study and Visualization Analysis. Med Sci Monit. 2023;29:e938673-1.
  4. Singal PK, Iliskovic N. Doxorubicin-induced cardiomyopathy. N Engl J Med. 1998;339:900–5.
  5. Huang KM, Zavorka Thomas M, Magdy T, et al. Targeting OCT3 attenuates doxorubicin-induced cardiac injury. Proc Natl Acad Sci U S A. 2021;118(5):e2020168118.
  6. Puhl SL. Cannabinoid-sensitive receptors in cardiac physiology and ischemia. Biochim Biophys Acta Mol Cell Res. 2020;1867(3):118462.
  7. Lim SY, Davidson SM, Yellon DM, Smith CC. The cannabinoid CB1 receptor antagonist, rimonabant, protects against acute myocardial infarction. Basic Res Cardiol. 2009;104:781–92.
  8. Lépicier P, Bibeau-Poirier A, Lagneux C, et al. Signaling pathways involved in the cardioprotective effects of cannabinoids. J Pharmacol Sci. 2006;102(2):155–66.
  9. Slavic S, Lauer D, Sommerfeld M, et al. Cannabinoid receptor 1 inhibition improves cardiac function and remodeling after myocardial infarction and in experimental metabolic syndrome. J Mol Med. 2013;91:811–23.
  10. Heimann AS, Gomes I, Dale CS, et al. Hemopressin is an inverse agonist of CB1 cannabinoid receptors. Proc Natl Acad Sci U S A. 2007;104:20588–93.
  11. Dodd GT, Worth AA, Hodkinson DJ, et al. Central functional response to the novel peptide cannabinoid, hemopressin. Neuropharmacology. 2013;71:27–36.
  12. Dale CS, Pagano RL, Rioli V. Hemopressin: a novel bioactive peptide derived from the alpha1-chain of hemoglobin. Mem Inst Oswaldo Cruz. 2005;100:105–6.
  13. Hama A, Sagen J. Centrally mediated antinociceptive effects of cannabinoid receptor ligands in rat models of nociception. Pharmacol Biochem Behav. 2011;100(2):340–6.
  14. Shan K, Lincoff AM, Young JB. Anthracycline-induced cardiotoxicity. Ann Intern Med. 1996;125(1):47–58.
  15. Koti BC, Nagathan S, Vishwanathswamy A, et al. Cardioprotective effect of Vedic Guard against doxorubicin- induced cardiotoxicity in rats: A biochemical, electrocardiographic, and histopathological study. Pharmacogn Mag. 2013;9(34):176–81.
  16. Fogaça MV, Sonego AB, Rioli V, et al. Anxiogenic-like effects induced by hemopressin in rats. Pharmacol Biochem Behav. 2015;129:7–13.
  17. Lippton, Howard et al. “Hemopressin, a hemoglobin fragment, dilates the rat systemic vascular bed through release of nitric oxide.” Peptides vol. 2006;27(9): 2284-8.
  18. Gül SS, & Aygün H. Cardioprotective effect of vitamin D and melatonin on doxorubicin-induced cardiotoxicity in rat model: an electrocardiographic, scintigraphic and biochemical study. The European Research Journal. 2019;5(4):649-57.
  19. Koroglu R, Koroglu M, Aygun H. Electrocardiographic, biochemical, and scintigraphic evidence for the cardioprotective effect of paricalcitol and vitamin D3 on doxorubicin-induced acute cardiotoxicity in rats. Bratisl Lek Listy. 2024;125(5):281-8.
  20. Nakahara T, Tanimoto T, Petrov AD, Ishikawa K, Strauss HW, Narula J. Rat Model of Cardiotoxic Drug-Induced Cardiomyopathy. Methods Mol Biol. 2018;1816:221-32.
  21. Avagimyan A, Madonna R, Sheibani M, Translational aspects of doxorubicin-induced cardiotoxicity: What we have omitted for the past decades? Vascul Pharmacol. 2025;7(160):107526.
  22. Todorova VK, Beggs ML, Delongchamp RR, et al. Transcriptome profiling of peripheral blood cells identifies potential biomarkers for doxorubicin cardiotoxicity in a rat model. PLoS One. 2012;7(11):e48398.
  23. Razmaraii N, Babaei H, Mohajjel Nayebi A, et al. Cardioprotective Effect of Phenytoin on Doxorubicin-induced Cardiac Toxicity in a Rat Model. J Cardiovasc Pharmacol. 2016;67(3):237-45.
  24. Momin FN, Kalai BR, Shikalgar TS, et al. Cardioprotective effect of methanolic extract of Ixora coccinea Linn. leaves on doxorubicin-induced cardiac toxicity in rats. Indian J Pharmacol. 2012;44(2):178–83.
  25. El-Agamy DS, Abo-Haded HM, Elkablawy MA. Cardioprotective effects of sitagliptin against doxorubicin- induced cardiotoxicity in rats. Exp Biol Med. 2016;241(14):1577–87.
  26. Aygun H, Gul SS. Cardioprotective effect of melatonin and agomelatine on doxorubicin-induced cardiotoxicity in a rat model: an electrocardiographic, scintigraphic and biochemical study. Bratisl Lek Listy. 2019;120(4):249–55.
  27. Rossi F, Filippelli W, Russo S, et al. Cardiotoxicity of doxorubicin: Effects of drugs inhibiting the release of vasoactive substances. Pharmacol Toxicol. 1994;75:99–107.
  28. Holland RP, Brooks H. TQ-ST segment mapping: Critical review and analysis of current concepts. Am J Cardiol. 1977;40:110–29.
  29. Yarmohammadi F, Rezaee R, Haye AW, et al. Endoplasmic reticulum stress in doxorubicin-induced cardiotoxicity may be therapeutically targeted by natural and chemical compounds: a review. Pharmacol Res. 2021;164:105383.
  30. Hadi N, Yousif NG, Al-Amran FG, et al. Vitamin E and telmisartan attenuate doxorubicin-induced cardiac injury in rats by downregulating inflammatory response. BMC Cardiovasc Disord. 2012;12:63.
  31. Wang L, Chen Q, Qi H, et al. Doxorubicin-induced systemic inflammation is driven by upregulation of toll-like receptor TLR4 and endotoxin leakage. Cancer Res. 2016;76:6631–42.
  32. Stark G. Functional consequences of oxidative membrane damage. J Membr Biol. 2005;205:1–16.
  33. Christenson ES, James T, Agrawal V, et al. Use of biomarkers for the assessment of chemotherapy-induced cardiac toxicity. Clin Biochem. 2015;48(4–5):223–35.
  34. Jean-Gilles L, Braitch M, Latif ML, et al. Effects of proinflammatory cytokines on cannabinoid CB1 and CB2 receptors in immune cells. Acta Physiol (Oxf). 2015;214:63–74.
  35. Huang NL, Juang JM, Wang YH, et al. Rimonabant inhibits TNF-α-induced endothelial IL-6 secretion via CB1 receptor and cAMP-dependent protein kinase pathway. Acta Pharmacol Sin. 2010;31(11):1447–53.
  36. Johnson A, Neumann PH, Peng J, et al. The intracerebroventricular injection of rimonabant inhibits systemic lipopolysaccharide-induced lung inflammation. J Neuroimmunol. 2015;286:16–24.
  37. Maeda N, Osanai T, Kushibiki M, et al. Increased serum anandamide level at ruptured plaque site in patients with acute myocardial infarction. Fundam Clin Pharmacol. 2009;23(3):351–7.
  38. Wang PF, Jiang LS, Bu J, et al. Cannabinoid-2 receptor activation protects against infarction and ischemia– reperfusion heart injury. J Cardiovasc Pharmacol. 2012;59(4):301–7.
  39. Lee JD, Schatz D, Hochman J. Cannabis and heart disease: forward into the great unknown? J Am Coll Cardiol. 2018;71(22):2552–4.
  40. Mukhopadhyay P, Bátkai S, Rajesh M, et al. Pharmacological inhibition of the CB1 cannabinoid receptor protects against doxorubicin-induced cardiotoxicity. J Am Coll Cardiol. 2007;50(6):528–36.
  41. Bonte FJ, Parkey RW, Graham KD, et al. A new method for radionuclide imaging of myocardial infarcts. Radiology. 1974;110(2):473–4.
  42. Stokely EM, Buja LM, Lewis SE, et al. Measurement of acute myocardial infarcts in dogs with 99mTc-stannous pyrophosphate scintigrams. J Nucl Med. 1976;17(1):1–5.
  43. Lee MC, Chung JK, Lee DS, et al. In anti-myosin monoclonal antibody in the detection of doxorubicin cardiotoxicity: a comparison with histology and Tc pyrophosphate. J Nucl Med. 1993;34(2):107–15.
  44. Aygun H, Basol N, Gul SS. Cardioprotective effect of paricalcitol on amitriptyline-induced cardiotoxicity in rats: comparison of [99mTc] PYP cardiac scintigraphy with electrocardiographic and biochemical findings. Cardiovasc Toxicol. 2020;20:427–36.
  45. Basol N, Aygun H, Gul SS. Beneficial effects of edaravone in an experimental model of amitriptyline-induced cardiotoxicity in rats. Naunyn Schmiedebergs Arch Pharmacol. 2019;392:1447–53.
  46. Mukhopadhyay P, Pan H, Rajesh M, et al. CB1 cannabinoid receptors promote oxidative/nitrosative stress, inflammation and cell death in a murine nephropathy model. Br J Pharmacol. 2010;160(3):657-68.
  47. Beyer CE, Dwyer JM, Piesla MJ, et al. Depression-like phenotype following chronic CB1 receptor antagonism. Neurobiol Dis. 2010;39(2):148-55.
  48. Camargo LL, Denadai-Souza A, Yshii LM, et al. The potential anti-inflammatory and anti-nociceptive effects of rat hemopressin (PVNFKFLSH) in experimental arthritis. Eur J Pharmacol. 2021;5(890):173636.
  49. Pietrasik G, Goldenberg I, Zdzienicka J, et al. Prognostic significance of fragmented QRS complex for predicting the risk of recurrent cardiac events in patients with Q-wave myocardial infarction. Am J Cardiol. 2007;100(4):583-6.
  50. Take Y, Morita H. Fragmented QRS: What Is The Meaning? Indian Pacing Electrophysiol J. 2012;12(5):213-25.
  51. Güz G. Yoğun bakım COVID-19 hastalarında EKG'de fragmente QRS varlığının yoğun bakım yatış süresi ve mortaliteye etkisi. Kocatepe Tıp Dergisi. 2023;24(2):201-5.