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Investigation of Protective Effects of Naringin on ECG, Cardiac Enzymes, Cardiac Histopathology and 8-OHdG Expression in Cyclophosphamide-Induced Cardiotoxicity in Rats

Year 2021, Volume: 16 Issue: 2, 196 - 203, 31.10.2021
https://doi.org/10.17094/ataunivbd.870668

Abstract

This study aimed to investigate the protective effects of Naringin in Cyclophosphamide (CYP)-induced cardiotoxicity in rats. In the study, forty male adult Sprague Dawley rats weighing approximately 200-250 g were used. Rats were divided into 5 experimental groups as control, CYP, Naringin50+CYP, Naringin100+CYP and Naringin100. Control and CYP groups were administered to intragastric (i.g.) saline for 10 days. Also, the CYP group was given a single dose of CYP (200 mg/kg, intraperitoneal (i.p.)) on the 10th day. Naringin50+CYP and Naringin100+CYP groups were administered i.g. 50 and 100 mg/kg doses of Naringin for 10 days, respectively, and was given a single dose of CYP (200mg/kg, intraperitoneal (i.p.)) on the 10th day. Naringin100 group was administered to Naringin (100mg/kg), i.g.) for 10 days. ECG was recorded under anesthesia, and intracardiac blood samples were taken. Troponin I, creatine kinase (CK) and creatine kinase-MB (CK-MB) parameters were examined in serum samples. As a result of the necropsy, preparations were prepared by routine cardiac tissue follow-up method for histopathological examination. For the detection of DNA damage in the cardiac tissue, 8-OHdG expression was investigated. CYP has been shown to have cardiotoxic effects on ECG values, cardiac enzymes, and cardiac histopathology of rats. In this study, it was determined that Naringin has a protective effect in CYP-induced cardiotoxicity in rats.

References

  • 1. Ghobadi E., Moloudizargari M., Asghari MH., Abdollahi M., 2017. The mechanisms of cyclophosphamide-induced testicular toxicity and the protective agents. Expert Opin Drug Metab Toxicol, 13, 525-536.
  • 2. Şengül E., Gelen V., Gedikli S., Özkanlar S., Gür C., Kara A., Çelebi F., Çınar A., 2017. Protective effect of quercetin on cyclophosphamide-induced lung toxicity in rats. Biomed Pharmacother, 92, 303-307.
  • 3. Gedikli S., Sengul E., 2019. Ratlarda siklofosfamid ile indüklenen hepatotoksisite üzerine kuersetinin etkileri. Dicle Tıp Derg, 46, 41-50.
  • 4. Yaman Bülbül G., Mis L., Şengül E., Yıldırım S., Çelebi F., Çınar DA., 2018. Cyclophosphamide ile indüklenmiş ratlarda karaciğer enzimleri (AST, ALT, ALP) ve histopatolojisi üzerine Naringinin protektif etkileri. Atatürk Üniversitesi Vet Bil Derg, 13, 182-190.
  • 5. Sengul E., Gelen V., Gedikli S., 2021. Cardioprotective activities of quercetin and rutin in sprague dawley rats treated with 5-fluorouracil. J Anim Plant Sci, 31, 423-431.
  • 6. Dağ Y., Sengul E., Selçuk M., Yıldırım S., Çelebi F., Çınar DA., 2018. Ratlarda cyclophosphamide ile indüklenen nefrotoksisitede bazı hematolojik parametreler ve böbreğin histopatolojisi üzerine Naringinin protektif etkileri. Atatürk Üniversitesi Vet Bil Derg, 13, 219-228.
  • 7. Gelen V., Sengul E., Yıldırım S., Celebi F., Cınar A., 2018. Effects of rutin on bladder contractility and histopathology in cyclophosphamide-induced hemorrhagic cystitis in rats. Atatürk Üniversitesi Vet Bil Derg, 13(3), 337-346.
  • 8. Gelen V., Sengul E., Gedikli S., Atila G., Uslu H., Makav M., 2017. The protective effect of rutin and quercetin on 5-FU-induced hepatotoxicity in rats. Asian Pac J Trop Biomed, 7, 647-653.
  • 9. Sengul E., Gelen SU., Yıldırım S., Çelebi F., Çınar A., 2019. Probiotic bacteria attenuates cisplatin-induced nephrotoxicity through modulation of oxidative stress, inflammation and apoptosis in rats. Asian Pac J Trop Biomed, 9, 116.
  • 10. Gelen V., Sengul E., Yıldırım S., Atila G., 2018. The protective effects of Naringin against 5-fluorouracil-induced hepatotoxicity and nephrotoxicity in rats. Iran J Basic Med Sci, 21, 404-410.
  • 11. Çelebi F., Cengiz I., Cinar DA., Sengul E., 2020. Siklofosfamidle indüklenmiş ratlarda serbest radikaller ve antioksidanlar üzerine Naringinin protektif etkileri. Atatürk Üniversitesi Vet Bil Derg, 15, 231-236.
  • 12. Çınar A., Yörük M., Meral İ., Kiliçalp D., Koç A., Ertekin A., 1999. Karbon tetraklörür (CCl4) ile tavşanlarda deneysel olarak oluşturulan akut ve kronik intoksikasyonun karaciğerin histolojik yapısına, bazı hematolojik değerlere ve elektrokardiyogram üzerine etkileri. Turkish J Vet Anim Sci, 23, 235-242.
  • 13. Yılmaz B., 1988. Kobaylarda elektrokardiyogram. AÜ Vet Fak Derg, 35, 309-316.
  • 14. Edwards NJ., 1987. Bolton’s Handbook of Canine and Feline Electrocardiography. 2st Ed., WB Saunders Company, Philadelphia.
  • 15. Bulduk B., Kılınç KD., 2013. Günlük crataegus oxyacatha (Alıç) uygulamasının ratlarda EKG değerlerine etkisi. YYU Vet Fak Derg, 24, 77-81.
  • 16. Baillard C., Mansier P., Ennezat PV., Mangin L., Medigue C., Swynghedauw B., 2000. Converting enzyme inhibition normalizes QT interval in spontaneously hypertensive rats. Hypertension, 36, 350-354.
  • 17. Kılıçalp D., Değer Y., Çınar A., 2009. Effects of green tea on electrocardiography of guinea pigs exposed to electromagnetic field emitted by mobile phones. Kafkas Uni Vet Fak Derg, 15, 823-828.
  • 18. Iqubal A., Syed MA., Najmi AK., Ali J., Haque SE., 2020. Ameliorative effect of nerolidol on cyclophosphamide‐induced gonadal toxicity in Swiss Albino mice: Biochemical‐, histological‐and immunohistochemical‐based evidences. Andrologia, 52, e13535.
  • 19. Yeh ET., Tong AT., Lenihan DJ., Yusuf SW., Swafford J., 2004. Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management. Circulation, 109, 3122-3131.
  • 20. Gelen V., Sengul E., 2020. Antioxidant, anti-inflammatory and antiapoptotic effects of Naringin on cardiac damage induced by cisplatin. Indian J Tradit Know, 19, 459-465.
  • 21. Bolton GR., 1975. Handbook of Canine Electrocardiography. WB Saunders Co, Philadelphia.
  • 22. Sambhi MP., White FN., 1960. The electrocardiogram of the normal and hypertensive rat. Am Heart Monogr S, 8, 129-134.
  • 23. Fraiser LH., Kanekal S., Kehrer JP., 1991. Cyclophosphamide toxicity. Characterising and avoiding the problem. Drugs, 42, 781-795.
  • 24. Gottdiener JS., Appelbaum FR., Ferrans VJ., Deisseroth A., Ziegler J., 1981. Cardiotoxicity associate with high-dose cyclophosphamide therapy. Arch Intern Med, 141, 758-763.
  • 25. Comba B., Çınar DA., Comba A., Gencer YG., 2016. Sıçanlarda ACTH uygulamasının böbrek fonksiyon testleri elektrolitler ve hematolojik parametreler üzerine etkileri. Ankara Üniversitesi Vet Fak Derg, 63, 229-233.
  • 26. Mills BA., Roberts RW., 1979. Cyclophosphamide-induced cardiomyopathy. Cancer, 43, 2223-2226.
  • 27. Morandi P., Ruffini PA., Benvenuto GM., Raimondi R., Fosser V., 2005. Cardiac toxicity of high dose chemotherapy. Bone Marrow Transplant, 35, 323-334.
  • 28. Stanton ME., Legendre AM., 1986. Effects of cyclophosphamide in dogs and cats. JAWMA, 188, 1319-1322.
  • 29. Schwartz PJ., Stramba BM., 1998. Prolongation of the QT interval and the sudden infant death syndrome. New Engl J Med, 338, 1709-1714.
  • 30. Kilicalp D., Cinar A., Belge F., 2004. Effects of chronic fluorosis on electrocardiogram in dogs. Fluoride, 37, 96-101.
  • 31. Kılıçalp D., Çınar A., 2003. The investigation of the effects of age, sex and season on electrocardiograms (ECG values) and heart radiographs of healty van cats. Tr J Vet Anim Sci, 27, 101-107.
  • 32. Cieslar G., Sieron A., Rzepka E., Zmudzsinski J., Franek A., 1986. Normal electrocardiogram in guinea pig. Acta Physiol, 37, 139-149.

Sıçanlarda Siklofosfamid ile İndüklenen Kardiyotoksisitede EKG, Kardiyak Enzimler, Kardiyak Histopatoloji ve 8-OHdG Ekspresyonu Üzerine Naringin’in Protektif Etkilerinin Araştırılması

Year 2021, Volume: 16 Issue: 2, 196 - 203, 31.10.2021
https://doi.org/10.17094/ataunivbd.870668

Abstract

Bu çalışmada, sıçanlarda Siklofosfamid (CYP) ile indüklenen kardiyotoksisitede Naringin'in koruyucu etkilerinin araştırılması amaçlandı. Çalışmada, ortalama 200-250 gr ağırlığında kırk adet erkek yetişkin Sprague Dawley sıçan kullanıldı. Sıçanlar kontrol, CYP, Naringin 50+CYP, Naringin100+CYP ve Naringin100 olmak üzere 5 deney grubuna ayrıldı. Kontrol ve CYP gruplarına, 10 gün intragastrik (i.g.) serum fizyolojik uygulandı. Ayrıca, CYP 10. gün tek doz CYP (200 mg/kg, intraperitoneal (i.p.)) verildi. Naringin 50+CYP ve Naringin100+CYP gruplarına, 10 gün boyunca sırasıyla 50 ve 100 mg/kg dozunda i.g. Naringin verildi ve 10. gün tek doz CYP (200 mg/kg, i.p.) verildi. Naringin100 grubuna ise, 10 gün 100 mg/kg dozunda i.g. Naringin verildi. Anestezi altında EKG kaydı yapıldı ve intrakardiyak kan örnekleri alındı. Serum örneklerinde Troponin I, kreatin kinaz (CK) ve kreatin kinaz-MB (CK-MB) parametreleri incelendi. Otopsi sonucunda histopatolojik inceleme için rutin kalp dokusu takip yöntemi ile preparatlar hazırlandı. Kalp dokusunda DNA hasarının tespiti için 8-OHdG ekspresyonu araştırıldı. CYP'nin sıçanların EKG değerleri, kardiyak enzimleri ve kardiyak histopatolojisi üzerinde kardiyotoksik etkileri olduğu gösterilmiştir. Bu çalışmada, sıçanlarda CYP ile indüklenen kardiyotoksisitede Naringin’in koruyucu etkilere sahip olduğu belirlendi.

References

  • 1. Ghobadi E., Moloudizargari M., Asghari MH., Abdollahi M., 2017. The mechanisms of cyclophosphamide-induced testicular toxicity and the protective agents. Expert Opin Drug Metab Toxicol, 13, 525-536.
  • 2. Şengül E., Gelen V., Gedikli S., Özkanlar S., Gür C., Kara A., Çelebi F., Çınar A., 2017. Protective effect of quercetin on cyclophosphamide-induced lung toxicity in rats. Biomed Pharmacother, 92, 303-307.
  • 3. Gedikli S., Sengul E., 2019. Ratlarda siklofosfamid ile indüklenen hepatotoksisite üzerine kuersetinin etkileri. Dicle Tıp Derg, 46, 41-50.
  • 4. Yaman Bülbül G., Mis L., Şengül E., Yıldırım S., Çelebi F., Çınar DA., 2018. Cyclophosphamide ile indüklenmiş ratlarda karaciğer enzimleri (AST, ALT, ALP) ve histopatolojisi üzerine Naringinin protektif etkileri. Atatürk Üniversitesi Vet Bil Derg, 13, 182-190.
  • 5. Sengul E., Gelen V., Gedikli S., 2021. Cardioprotective activities of quercetin and rutin in sprague dawley rats treated with 5-fluorouracil. J Anim Plant Sci, 31, 423-431.
  • 6. Dağ Y., Sengul E., Selçuk M., Yıldırım S., Çelebi F., Çınar DA., 2018. Ratlarda cyclophosphamide ile indüklenen nefrotoksisitede bazı hematolojik parametreler ve böbreğin histopatolojisi üzerine Naringinin protektif etkileri. Atatürk Üniversitesi Vet Bil Derg, 13, 219-228.
  • 7. Gelen V., Sengul E., Yıldırım S., Celebi F., Cınar A., 2018. Effects of rutin on bladder contractility and histopathology in cyclophosphamide-induced hemorrhagic cystitis in rats. Atatürk Üniversitesi Vet Bil Derg, 13(3), 337-346.
  • 8. Gelen V., Sengul E., Gedikli S., Atila G., Uslu H., Makav M., 2017. The protective effect of rutin and quercetin on 5-FU-induced hepatotoxicity in rats. Asian Pac J Trop Biomed, 7, 647-653.
  • 9. Sengul E., Gelen SU., Yıldırım S., Çelebi F., Çınar A., 2019. Probiotic bacteria attenuates cisplatin-induced nephrotoxicity through modulation of oxidative stress, inflammation and apoptosis in rats. Asian Pac J Trop Biomed, 9, 116.
  • 10. Gelen V., Sengul E., Yıldırım S., Atila G., 2018. The protective effects of Naringin against 5-fluorouracil-induced hepatotoxicity and nephrotoxicity in rats. Iran J Basic Med Sci, 21, 404-410.
  • 11. Çelebi F., Cengiz I., Cinar DA., Sengul E., 2020. Siklofosfamidle indüklenmiş ratlarda serbest radikaller ve antioksidanlar üzerine Naringinin protektif etkileri. Atatürk Üniversitesi Vet Bil Derg, 15, 231-236.
  • 12. Çınar A., Yörük M., Meral İ., Kiliçalp D., Koç A., Ertekin A., 1999. Karbon tetraklörür (CCl4) ile tavşanlarda deneysel olarak oluşturulan akut ve kronik intoksikasyonun karaciğerin histolojik yapısına, bazı hematolojik değerlere ve elektrokardiyogram üzerine etkileri. Turkish J Vet Anim Sci, 23, 235-242.
  • 13. Yılmaz B., 1988. Kobaylarda elektrokardiyogram. AÜ Vet Fak Derg, 35, 309-316.
  • 14. Edwards NJ., 1987. Bolton’s Handbook of Canine and Feline Electrocardiography. 2st Ed., WB Saunders Company, Philadelphia.
  • 15. Bulduk B., Kılınç KD., 2013. Günlük crataegus oxyacatha (Alıç) uygulamasının ratlarda EKG değerlerine etkisi. YYU Vet Fak Derg, 24, 77-81.
  • 16. Baillard C., Mansier P., Ennezat PV., Mangin L., Medigue C., Swynghedauw B., 2000. Converting enzyme inhibition normalizes QT interval in spontaneously hypertensive rats. Hypertension, 36, 350-354.
  • 17. Kılıçalp D., Değer Y., Çınar A., 2009. Effects of green tea on electrocardiography of guinea pigs exposed to electromagnetic field emitted by mobile phones. Kafkas Uni Vet Fak Derg, 15, 823-828.
  • 18. Iqubal A., Syed MA., Najmi AK., Ali J., Haque SE., 2020. Ameliorative effect of nerolidol on cyclophosphamide‐induced gonadal toxicity in Swiss Albino mice: Biochemical‐, histological‐and immunohistochemical‐based evidences. Andrologia, 52, e13535.
  • 19. Yeh ET., Tong AT., Lenihan DJ., Yusuf SW., Swafford J., 2004. Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management. Circulation, 109, 3122-3131.
  • 20. Gelen V., Sengul E., 2020. Antioxidant, anti-inflammatory and antiapoptotic effects of Naringin on cardiac damage induced by cisplatin. Indian J Tradit Know, 19, 459-465.
  • 21. Bolton GR., 1975. Handbook of Canine Electrocardiography. WB Saunders Co, Philadelphia.
  • 22. Sambhi MP., White FN., 1960. The electrocardiogram of the normal and hypertensive rat. Am Heart Monogr S, 8, 129-134.
  • 23. Fraiser LH., Kanekal S., Kehrer JP., 1991. Cyclophosphamide toxicity. Characterising and avoiding the problem. Drugs, 42, 781-795.
  • 24. Gottdiener JS., Appelbaum FR., Ferrans VJ., Deisseroth A., Ziegler J., 1981. Cardiotoxicity associate with high-dose cyclophosphamide therapy. Arch Intern Med, 141, 758-763.
  • 25. Comba B., Çınar DA., Comba A., Gencer YG., 2016. Sıçanlarda ACTH uygulamasının böbrek fonksiyon testleri elektrolitler ve hematolojik parametreler üzerine etkileri. Ankara Üniversitesi Vet Fak Derg, 63, 229-233.
  • 26. Mills BA., Roberts RW., 1979. Cyclophosphamide-induced cardiomyopathy. Cancer, 43, 2223-2226.
  • 27. Morandi P., Ruffini PA., Benvenuto GM., Raimondi R., Fosser V., 2005. Cardiac toxicity of high dose chemotherapy. Bone Marrow Transplant, 35, 323-334.
  • 28. Stanton ME., Legendre AM., 1986. Effects of cyclophosphamide in dogs and cats. JAWMA, 188, 1319-1322.
  • 29. Schwartz PJ., Stramba BM., 1998. Prolongation of the QT interval and the sudden infant death syndrome. New Engl J Med, 338, 1709-1714.
  • 30. Kilicalp D., Cinar A., Belge F., 2004. Effects of chronic fluorosis on electrocardiogram in dogs. Fluoride, 37, 96-101.
  • 31. Kılıçalp D., Çınar A., 2003. The investigation of the effects of age, sex and season on electrocardiograms (ECG values) and heart radiographs of healty van cats. Tr J Vet Anim Sci, 27, 101-107.
  • 32. Cieslar G., Sieron A., Rzepka E., Zmudzsinski J., Franek A., 1986. Normal electrocardiogram in guinea pig. Acta Physiol, 37, 139-149.
There are 32 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Araştırma Makaleleri
Authors

Yavuz Kolikpınar This is me 0000-0003-2334-9320

Yusuf Dağ This is me 0000-0003-0784-5826

Samet Tekin 0000-0003-4116-6720

Serkan Yıldırım 0000-0003-2457-3367

Pelin Durukan Azman This is me 0000-0001-8379-6670

Aslıhan Atasever This is me 0000-0002-2983-3343

Merve Bolat This is me 0000-0001-5836-5529

Burak Batuhan Laçin 0000-0002-5701-3684

Melehat Gök This is me 0000-0001-5177-0118

Özlem Erol Polat 0000-0002-2618-9601

Ali Cınar 0000-0002-3928-320X

Publication Date October 31, 2021
Published in Issue Year 2021 Volume: 16 Issue: 2

Cite

APA Kolikpınar, Y., Dağ, Y., Tekin, S., Yıldırım, S., et al. (2021). Investigation of Protective Effects of Naringin on ECG, Cardiac Enzymes, Cardiac Histopathology and 8-OHdG Expression in Cyclophosphamide-Induced Cardiotoxicity in Rats. Atatürk Üniversitesi Veteriner Bilimleri Dergisi, 16(2), 196-203. https://doi.org/10.17094/ataunivbd.870668
AMA Kolikpınar Y, Dağ Y, Tekin S, Yıldırım S, Durukan Azman P, Atasever A, Bolat M, Laçin BB, Gök M, Erol Polat Ö, Cınar A. Investigation of Protective Effects of Naringin on ECG, Cardiac Enzymes, Cardiac Histopathology and 8-OHdG Expression in Cyclophosphamide-Induced Cardiotoxicity in Rats. Atatürk Üniversitesi Veteriner Bilimleri Dergisi. October 2021;16(2):196-203. doi:10.17094/ataunivbd.870668
Chicago Kolikpınar, Yavuz, Yusuf Dağ, Samet Tekin, Serkan Yıldırım, Pelin Durukan Azman, Aslıhan Atasever, Merve Bolat, Burak Batuhan Laçin, Melehat Gök, Özlem Erol Polat, and Ali Cınar. “Investigation of Protective Effects of Naringin on ECG, Cardiac Enzymes, Cardiac Histopathology and 8-OHdG Expression in Cyclophosphamide-Induced Cardiotoxicity in Rats”. Atatürk Üniversitesi Veteriner Bilimleri Dergisi 16, no. 2 (October 2021): 196-203. https://doi.org/10.17094/ataunivbd.870668.
EndNote Kolikpınar Y, Dağ Y, Tekin S, Yıldırım S, Durukan Azman P, Atasever A, Bolat M, Laçin BB, Gök M, Erol Polat Ö, Cınar A (October 1, 2021) Investigation of Protective Effects of Naringin on ECG, Cardiac Enzymes, Cardiac Histopathology and 8-OHdG Expression in Cyclophosphamide-Induced Cardiotoxicity in Rats. Atatürk Üniversitesi Veteriner Bilimleri Dergisi 16 2 196–203.
IEEE Y. Kolikpınar, “Investigation of Protective Effects of Naringin on ECG, Cardiac Enzymes, Cardiac Histopathology and 8-OHdG Expression in Cyclophosphamide-Induced Cardiotoxicity in Rats”, Atatürk Üniversitesi Veteriner Bilimleri Dergisi, vol. 16, no. 2, pp. 196–203, 2021, doi: 10.17094/ataunivbd.870668.
ISNAD Kolikpınar, Yavuz et al. “Investigation of Protective Effects of Naringin on ECG, Cardiac Enzymes, Cardiac Histopathology and 8-OHdG Expression in Cyclophosphamide-Induced Cardiotoxicity in Rats”. Atatürk Üniversitesi Veteriner Bilimleri Dergisi 16/2 (October 2021), 196-203. https://doi.org/10.17094/ataunivbd.870668.
JAMA Kolikpınar Y, Dağ Y, Tekin S, Yıldırım S, Durukan Azman P, Atasever A, Bolat M, Laçin BB, Gök M, Erol Polat Ö, Cınar A. Investigation of Protective Effects of Naringin on ECG, Cardiac Enzymes, Cardiac Histopathology and 8-OHdG Expression in Cyclophosphamide-Induced Cardiotoxicity in Rats. Atatürk Üniversitesi Veteriner Bilimleri Dergisi. 2021;16:196–203.
MLA Kolikpınar, Yavuz et al. “Investigation of Protective Effects of Naringin on ECG, Cardiac Enzymes, Cardiac Histopathology and 8-OHdG Expression in Cyclophosphamide-Induced Cardiotoxicity in Rats”. Atatürk Üniversitesi Veteriner Bilimleri Dergisi, vol. 16, no. 2, 2021, pp. 196-03, doi:10.17094/ataunivbd.870668.
Vancouver Kolikpınar Y, Dağ Y, Tekin S, Yıldırım S, Durukan Azman P, Atasever A, Bolat M, Laçin BB, Gök M, Erol Polat Ö, Cınar A. Investigation of Protective Effects of Naringin on ECG, Cardiac Enzymes, Cardiac Histopathology and 8-OHdG Expression in Cyclophosphamide-Induced Cardiotoxicity in Rats. Atatürk Üniversitesi Veteriner Bilimleri Dergisi. 2021;16(2):196-203.