Öz
Background: Cyclophosphamide (CP), an agent used in antineoplastic chemotherapy, has toxic effects on many tissues. In this study, the protective effects of thymoquinone (TQ), the dominant component of black cumin essential oil, against cyclophosphamide-induced cardiotoxicity were investigated.
Materials and Methods: Thirty-two 8-week-old male Sprague Dawley rats were divided into 4 groups (n=8); control, TQ (10 mg/kg/day, oral gavage), CP (50 mg/kg, i.p., on days 1, 8, 15 and 22), and TQ+CP (TQ 10 mg/kg/day, oral gavage and CP 50 mg/kg, i.p. on days 1, 8, 15 and 22). After four weeks of applications, histopathological and biochemical analyzes were performed on heart tissues.
Results: It was observed that CP caused a significant increase in malondialdehyde (MDA) levels in heart tissues (p<0.001), and the addition of TQ reduced the CP-induced increase in MDA levels to normal levels. Histological preparations stained with hematoxylin and eosin (H&E), Masson’s trichrome and Toluidine Blue revealed histopathological changes in heart tissues between groups. TQ supplementation was found to have a positive effect on the biochemical and histological changes induced by CP.
Conclusions: In this study, TQ was found to have a protective effect against cardiotoxicity by reducing CP-induced oxidative damage.
Anahtar Kelimeler
Cyclophosphamide Thymoquinone Malondialdehyde Cardiotoxicity.
Proje Numarası
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Kaynakça
- Aksoy, F., Dogan, R., Ozturan, O., Tugrul, S., Veyseller, B., Ozer, O.F. & Pektas, A. (2015). An evaluation of the protective effects of thymoquinone on amikacin-induced ototoxicity in rats. Clinical and experimental otorhinolaryngology, 8(4), 312-319.
- Aktaş, İ. & Mehmet Gür, F. (2022). Hepato-protective effects of thymoquinone and beta-aminoisobutyric acid in streptozocin induced diabetic rats. Biotechnic & Histochemistry, 97(1), 67-76.
- Alenzi, F.Q., El-Bolkiny, Y.E.S. & Salem, M.L. (2010). Protective effects of Nigella sativa oil and thymoquinone against toxicity induced by the anticancer drug cyclophosphamide. British journal of biomedical science, 67(1), 20-28.
- Ali, B.H. & Blunden, G. (2003). Pharmacological and toxicological properties of Nigella sativa. Phytotherapy Research: An international journal devoted to pharmacological and toxicological evaluation of natural product derivatives, 17(4), 299-305.
- Argun, M. (2015). Hematolojik malign hastalıklarda kalp tutulumu ve kemoterapi kardiyotoksisitesi. Turkiye Klinikleri J Pediatr Sci, 11(2), 60-5.
- Aydin, M.S., Kocarslan, A., Kocarslan, S., Kucuk, A., Eser, İ., Sezen, H.,... & Hazar, A. (2015). Thymoquinone protects end organs from abdominal aorta ischemia/reperfusion injury in a rat model. Brazilian Journal of Cardiovascular Surgery, 30, 77-83.
- Ayhanci, A., Uyar, R., Aral, E., Kabadere, S. & Appak, S. (2008). Protective effect of zinc on cyclophosphamide-induced hematoxicity and urotoxicity. Biological trace element research, 126, 186-193.
- Ayza, M.A., Zewdie, K.A., Tesfaye, B.A., Wondafrash, D.Z. & Berhe, A.H. (2020). The role of antioxidants in ameliorating cyclophosphamide-ınduced cardiotoxicity. Oxidative Medicine and Cellular Longevity, 2020, 1–14.
- Beutler, E. Glutathione in Red Cell Metabolism : A Manual of Biochemical methods. 2nd ed., Grune and Stratton, NY, 1975, p:112-114.
- Buege, J.A. & Aust, S.D. (1978). [30] Microsomal lipid peroxidation. In Methods in enzymology (Vol. 52, pp. 302-310). Academic press.
- Cengiz, M. (2018). Ratlarda siklofosfamid nedenli kardiyotoksisite üzerine borik asitin koruyucu etkileri. Bitlis Eren Üniversitesi Fen Bilimleri Dergisi, 7(1), 113-118.
- Cetik, S. (2014). Sıçanlarda Siklofosfamid Nedenli Kardiyotoksisitede Oksidatif Stres ve Kalp Hasarına Karşı Karvakrol’ün Koruyucu Etkisi. Eskişehir Osmangazi Üniversitesi. Fen Bilimleri Enstitüsü, Doktora Tezi, Eskişehir.
- Chaudhary, P., Janmeda, P., Docea, A. O., Yeskaliyeva, B., Abdull Razis, A. F., Modu, B., ... & Sharifi-Rad, J. (2023). Oxidative stress, free radicals and antioxidants: potential crosstalk in the pathophysiology of human diseases. Frontiers in chemistry, 11, 1158198.
- Darakhshan, S., Pour, A.B., Colagar, A.H. & Sisakhtnezhad, S. (2015). Thymoquinone and its therapeutic potentials. Pharmacological research, 95, 138-158.
- Fraiser, L.H., Kanekal, S. & Kehrer, J.P. (1991). Cyclophosphamide toxicity: characterising and avoiding the problem. Drugs, 42, 781-795.
- Goyal, S., Arora, S., Bhatt, T. K., Das, P., Sharma, A., Kumari, S. & Arya, D. S. (2010). Modulation of PPAR-γ by telmisartan protects the heart against myocardial infarction in experimental diabetes. Chemico-biological interactions, 185(3), 271-280.
- Günes, S. (2014). Siklofosfamid nedenli doku hasarı ve oksidatif stres üzerine selenyumun etkisi. (Yüksek lisans tezi). Eskişehir Osmangazi Üniversitesi. Sağlık Bilimleri Enstitüsü. Fizyoloji Ana Bilim Dalı. Ulusal tez merkezi. (396492).
- Isaev, N.K., Genrikhs, E.E. & Stelmashook, E.V. (2023). Antioxidant thymoquinone and its potential in the treatment of neurological diseases. Antioxidants, 12(2), 433.
- Karabulut, D., Ozturk, E., Kaymak, E., Akin, A.T. & Yakan, B. (2021). Thymoquinone attenuates doxorubicin‐cardiotoxicity in rats. Journal of biochemical and molecular toxicology, 35(1), e22618.
- Kaya, E., Yılmaz, S. & Çolakoğlu, N. (2018). Ratlarda siklofosfamidin sebep olduğu kardiyotoksisitede propolisin koruyucu rolü. Ankara Üniversitesi Veteriner Fakültesi Dergisi, 66(1), 13-20.
- Kumar, K.B.H. & Kuttan, R. (2005). Chemoprotective activity of an extract of phyllanthus amarus against cyclophosphamide induced toxicity in mice. Phytomedicine, 12(6-7), 494-500.
- Kwon, D.H., Cha, H.J., Lee, H., Hong, S.H., Park, C., Park, S.H., ... & Choi, Y.H. (2019). Protective effect of glutathione against oxidative stress-induced cytotoxicity in RAW 264.7 macrophages through activating the nuclear factor erythroid 2-related factor-2/heme oxygenase-1 pathway. Antioxidants, 8(4), 82.
- Mabrouk, A. (2021). Thymoquinone ımproves lead-induced hematotoxicity in rats. Pakistan Journal of Zoology, 54, 1-9.
- Mythili, Y., Sudharsan, P.T., Selvakumar, E. & Varalakshmi, P. (2004). Protective effect of DL-α-lipoic acid on cyclophosphamide-induced oxidative cardiac injury. Chemico-biological interactions, 151(1), 13-19.
- Nagi, M.N., Al‐Shabanah, O.A., Hafez, M.M. & Sayed‐Ahmed, M.M. (2011). Thymoquinone supplementation attenuates cyclophosphamide‐induced cardiotoxicity in rats. Journal of biochemical and molecular toxicology, 25(3), 135-142.
- Parlar, A. & Arslan, S.O. (2020). Thymoquinone reduces ischemia and reperfusion-induced intestinal injury in rats, through anti-oxidative and anti-inflammatory effects. Turkish Journal of Surgery, 36(1), 96.
- Perini, P., Calabrese, M., Rinaldi, L. & Gallo, P. (2008). Cyclophosphamide-based combination therapies for autoimmunity. Neurological Sciences, 29, 233-234.
- Ray, S., Chowdhury, P., Pandit, B., Ray, S.D. & Das, S. (2010). Exploring the antiperoxidative potential of morin on cyclophosphamide and flutamide-induced lipid peroxidation and changes in cholesterol profile in rabbit model. Acta Pol Pharm., 67(1), 35-44.
- Staniek, K. & Gille, L. (2010, November). Is thymoquinone an antioxidant?. In BMC pharmacology (Vol. 10, No. 1, pp. 1-1). BioMed Central.
- Swamy, A.V., Patel, U.M., Koti, B.C., Gadad, P.C., Patel, N.L. & Thippeswamy, A.H.M. (2013). Cardioprotective effect of Saraca indica against cyclophosphamide induced cardiotoxicity in rats: a biochemical, electrocardiographic and histopathological study. Indian journal of pharmacology, 45(1), 44.
- Yıldız, S.Ç. & Gözüoğlu, G. (2021) Myeloprotective and hematoprotective role of kefir on cyclophosphamide toxicity in rats. Archives of Clinical and Experimental Medicine, 6(2), 77-82.
Öz
Amaç: Antineoplastik kemoterapide kullanılan bir ajan olan siklofosfamidin (CP) birçok doku üzerinde toksik etkisi bulunmaktadır. Bu çalışmada siklofosfamidin oluşturduğu kardiyotoksisiteye karşı çörek otu uçucu yağının baskın bileşeni olan Timokinonun (TQ) koruyucu etkileri araştırıldı.
Materyal ve Metot: Bu amaçla 32 adet 8 haftalık erkek Sprague Dawley sıçan 4 eşit gruba ayrıldı (n=8). Kontrol, TQ (10 mg/kg/gün, oral gavaj), CP (50 mg/kg, i.p., 1, 8, 15 ve 22. günlerde) ve TQ+CP (TQ 10 mg/kg/gün, oral gavaj ve CP 50 mg/kg, i.p., 1, 8, 15 ve 22. günlerde). Dört haftalık uygulamaların ardından kalp dokusunda histopatolojik ve biyokimyasal analizler yapıldı.
Bulgular: Kalp dokusunda CP’nin malondialdehit (MDA) seviyelerinde belirgin artışlara sebep olduğu (p<0.001), TQ ilavesinin siklofosfamidin sebep olduğu MDA seviyesindeki artışı azaltarak normal seviyelere getirdiği görüldü. Hematoksilen-Eozin (H&E), Masson trikrom boyama ve Toluidin Blue boyama yöntemi ile boyanan histolojik preperatlarda kalp dokusunda gruplar arasında histopatolojik değişiklikler tespit edildi. TQ takviyesinin, CP’nin sebep olduğu biyokimyasal ve histolojik değişiklikleri olumlu yönde etkilediği saptandı.
Sonuç: Bu çalışmada TQ’nun CP kaynaklı oksidatif hasarı azaltarak kardiyotoksisiteye karşı koruyucu bir etki gösterdiği tespit edildi.
Anahtar Kelimeler
Destekleyen Kurum
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Proje Numarası
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Teşekkür
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Kaynakça
- Aksoy, F., Dogan, R., Ozturan, O., Tugrul, S., Veyseller, B., Ozer, O.F. & Pektas, A. (2015). An evaluation of the protective effects of thymoquinone on amikacin-induced ototoxicity in rats. Clinical and experimental otorhinolaryngology, 8(4), 312-319.
- Aktaş, İ. & Mehmet Gür, F. (2022). Hepato-protective effects of thymoquinone and beta-aminoisobutyric acid in streptozocin induced diabetic rats. Biotechnic & Histochemistry, 97(1), 67-76.
- Alenzi, F.Q., El-Bolkiny, Y.E.S. & Salem, M.L. (2010). Protective effects of Nigella sativa oil and thymoquinone against toxicity induced by the anticancer drug cyclophosphamide. British journal of biomedical science, 67(1), 20-28.
- Ali, B.H. & Blunden, G. (2003). Pharmacological and toxicological properties of Nigella sativa. Phytotherapy Research: An international journal devoted to pharmacological and toxicological evaluation of natural product derivatives, 17(4), 299-305.
- Argun, M. (2015). Hematolojik malign hastalıklarda kalp tutulumu ve kemoterapi kardiyotoksisitesi. Turkiye Klinikleri J Pediatr Sci, 11(2), 60-5.
- Aydin, M.S., Kocarslan, A., Kocarslan, S., Kucuk, A., Eser, İ., Sezen, H.,... & Hazar, A. (2015). Thymoquinone protects end organs from abdominal aorta ischemia/reperfusion injury in a rat model. Brazilian Journal of Cardiovascular Surgery, 30, 77-83.
- Ayhanci, A., Uyar, R., Aral, E., Kabadere, S. & Appak, S. (2008). Protective effect of zinc on cyclophosphamide-induced hematoxicity and urotoxicity. Biological trace element research, 126, 186-193.
- Ayza, M.A., Zewdie, K.A., Tesfaye, B.A., Wondafrash, D.Z. & Berhe, A.H. (2020). The role of antioxidants in ameliorating cyclophosphamide-ınduced cardiotoxicity. Oxidative Medicine and Cellular Longevity, 2020, 1–14.
- Beutler, E. Glutathione in Red Cell Metabolism : A Manual of Biochemical methods. 2nd ed., Grune and Stratton, NY, 1975, p:112-114.
- Buege, J.A. & Aust, S.D. (1978). [30] Microsomal lipid peroxidation. In Methods in enzymology (Vol. 52, pp. 302-310). Academic press.
- Cengiz, M. (2018). Ratlarda siklofosfamid nedenli kardiyotoksisite üzerine borik asitin koruyucu etkileri. Bitlis Eren Üniversitesi Fen Bilimleri Dergisi, 7(1), 113-118.
- Cetik, S. (2014). Sıçanlarda Siklofosfamid Nedenli Kardiyotoksisitede Oksidatif Stres ve Kalp Hasarına Karşı Karvakrol’ün Koruyucu Etkisi. Eskişehir Osmangazi Üniversitesi. Fen Bilimleri Enstitüsü, Doktora Tezi, Eskişehir.
- Chaudhary, P., Janmeda, P., Docea, A. O., Yeskaliyeva, B., Abdull Razis, A. F., Modu, B., ... & Sharifi-Rad, J. (2023). Oxidative stress, free radicals and antioxidants: potential crosstalk in the pathophysiology of human diseases. Frontiers in chemistry, 11, 1158198.
- Darakhshan, S., Pour, A.B., Colagar, A.H. & Sisakhtnezhad, S. (2015). Thymoquinone and its therapeutic potentials. Pharmacological research, 95, 138-158.
- Fraiser, L.H., Kanekal, S. & Kehrer, J.P. (1991). Cyclophosphamide toxicity: characterising and avoiding the problem. Drugs, 42, 781-795.
- Goyal, S., Arora, S., Bhatt, T. K., Das, P., Sharma, A., Kumari, S. & Arya, D. S. (2010). Modulation of PPAR-γ by telmisartan protects the heart against myocardial infarction in experimental diabetes. Chemico-biological interactions, 185(3), 271-280.
- Günes, S. (2014). Siklofosfamid nedenli doku hasarı ve oksidatif stres üzerine selenyumun etkisi. (Yüksek lisans tezi). Eskişehir Osmangazi Üniversitesi. Sağlık Bilimleri Enstitüsü. Fizyoloji Ana Bilim Dalı. Ulusal tez merkezi. (396492).
- Isaev, N.K., Genrikhs, E.E. & Stelmashook, E.V. (2023). Antioxidant thymoquinone and its potential in the treatment of neurological diseases. Antioxidants, 12(2), 433.
- Karabulut, D., Ozturk, E., Kaymak, E., Akin, A.T. & Yakan, B. (2021). Thymoquinone attenuates doxorubicin‐cardiotoxicity in rats. Journal of biochemical and molecular toxicology, 35(1), e22618.
- Kaya, E., Yılmaz, S. & Çolakoğlu, N. (2018). Ratlarda siklofosfamidin sebep olduğu kardiyotoksisitede propolisin koruyucu rolü. Ankara Üniversitesi Veteriner Fakültesi Dergisi, 66(1), 13-20.
- Kumar, K.B.H. & Kuttan, R. (2005). Chemoprotective activity of an extract of phyllanthus amarus against cyclophosphamide induced toxicity in mice. Phytomedicine, 12(6-7), 494-500.
- Kwon, D.H., Cha, H.J., Lee, H., Hong, S.H., Park, C., Park, S.H., ... & Choi, Y.H. (2019). Protective effect of glutathione against oxidative stress-induced cytotoxicity in RAW 264.7 macrophages through activating the nuclear factor erythroid 2-related factor-2/heme oxygenase-1 pathway. Antioxidants, 8(4), 82.
- Mabrouk, A. (2021). Thymoquinone ımproves lead-induced hematotoxicity in rats. Pakistan Journal of Zoology, 54, 1-9.
- Mythili, Y., Sudharsan, P.T., Selvakumar, E. & Varalakshmi, P. (2004). Protective effect of DL-α-lipoic acid on cyclophosphamide-induced oxidative cardiac injury. Chemico-biological interactions, 151(1), 13-19.
- Nagi, M.N., Al‐Shabanah, O.A., Hafez, M.M. & Sayed‐Ahmed, M.M. (2011). Thymoquinone supplementation attenuates cyclophosphamide‐induced cardiotoxicity in rats. Journal of biochemical and molecular toxicology, 25(3), 135-142.
- Parlar, A. & Arslan, S.O. (2020). Thymoquinone reduces ischemia and reperfusion-induced intestinal injury in rats, through anti-oxidative and anti-inflammatory effects. Turkish Journal of Surgery, 36(1), 96.
- Perini, P., Calabrese, M., Rinaldi, L. & Gallo, P. (2008). Cyclophosphamide-based combination therapies for autoimmunity. Neurological Sciences, 29, 233-234.
- Ray, S., Chowdhury, P., Pandit, B., Ray, S.D. & Das, S. (2010). Exploring the antiperoxidative potential of morin on cyclophosphamide and flutamide-induced lipid peroxidation and changes in cholesterol profile in rabbit model. Acta Pol Pharm., 67(1), 35-44.
- Staniek, K. & Gille, L. (2010, November). Is thymoquinone an antioxidant?. In BMC pharmacology (Vol. 10, No. 1, pp. 1-1). BioMed Central.
- Swamy, A.V., Patel, U.M., Koti, B.C., Gadad, P.C., Patel, N.L. & Thippeswamy, A.H.M. (2013). Cardioprotective effect of Saraca indica against cyclophosphamide induced cardiotoxicity in rats: a biochemical, electrocardiographic and histopathological study. Indian journal of pharmacology, 45(1), 44.
- Yıldız, S.Ç. & Gözüoğlu, G. (2021) Myeloprotective and hematoprotective role of kefir on cyclophosphamide toxicity in rats. Archives of Clinical and Experimental Medicine, 6(2), 77-82.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Konular | Kardiyoloji , Sistem Fizyolojisi |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Proje Numarası | - |
| Yayımlanma Tarihi | 30 Aralık 2023 |
| Gönderilme Tarihi | 21 Ağustos 2023 |
| Yayımlandığı Sayı | Yıl 2023 Cilt: 2 Sayı: 3 |
