Araştırma Makalesi
Siklofosfamidle İndüklenmiş Ratlarda Serbest Radikaller ve Antioksidanlar Üzerine Naringinin Protektif Etkileri
Öz
Bu çalışmada siklofosfamid (CYP) ile uygulanan ratlarda kan ve serum örneklerinde Naringin (NA)’in antioksidanlar ve serbest radikaller üzerine protektif etkilerinin araştırılması amaçlandı. Araştırmamızda yaklaşık 200-250 g ağırlığında, 40 adet erkek erişkin Sprague Dawley rat kullanıldı ve her bir grupta 8 ratın bulunduğu 5 grup oluşturuldu. Kontrol grubuna 10 gün boyunca intra gastrik (i.g.) serum fizyolojik (1 ml) verildi. CYP grubuna 10 gün boyunca i.g. serum fizyolojik verildi ve 10. gün tek doz intra peritonal (i.p.) CYP (200 mg/kg) enjekte edildi. NA50+CYP ve NA100+CYP gruplarına 10 gün boyunca sırasıyla serum fizyolojikte çözdürülmüş 50 ve 100 mg/kg dozunda i.g. NA uygulandı ve NA’nın son enjeksiyondan sonra tek doz CYP (200 mg/kg, i.p.) enjekte edildi. NA100 grubuna ise 10 gün boyunca 100 mg/kg dozunda i.g. NA uygulandı. Deneyin 12. gününde ratlar tiopental sodyum (20 mg/kg) ile anestezi altına alınarak intra kardiyak kan örnekleri alındı ve dekapite edildiler. Ratlardan elde edilen kan ve serum örneklerinde Total Antioksidan Durumu (TAS), Total Oksidan Durumu (TOS), Oksidatif stres indeksi (OSİ) ve 8-Hydroxydeoxyguanosine (8-OHdG) parametreleri analiz edildi. CYP’nin ratlarda oksidatif stresi artırdığı, antioksidanları baskıladığı ve DNA hasarına yol açtığı tespit edildi. NA’nın farklı dozlarının, CYP’nin sebep olduğu oksidatif stresi baskıladığı, antioksidan miktarını artırdığı ve DNA hasarını önlediği belirlendi.
Anahtar Kelimeler
Kaynakça
- 1. Türker FA., Kayaalp SO., 2002. Kanser kemoterapisinin esasları ve antineoplastik ilaçlar. Rasyonel Tedavi Yönünden Tıbbi Farmakoloji. 380-415, Feryal Matbaacılık, Ankara. 2. Vollbracht C., Schneider B., Leendert V., Weiss G., Auerbach L., Beuth J., 2011. Intravenous vitamin C administration improves quality of life in breast cancer patients during chemo-/radiotherapy and aftercare: results of a retrospective, multicentre, epidemiological cohort study in Germany. In vivo, 25, 983-990. 3. Kintzel PE., 2001. Anticancer drug-induced kidney disorders. Incidence, prevention and management. Drug Safety, 24, 19-38. 4. Tripathi DN., Jena GB., 2008. Astaxanthin inhibits cytotoxic and genotoxic effects of cyclophosphamide in mice germ cells. Toxicology, 248, 96-103. 5. Al-Safi SA., Maddocks JL., 1986. Does 2-Mercaptoethane Sulphonate (mesna) Prevent Cyclophosphamide and Azathioprine Induced İmmunosuppression? In vitro studies. Br J Clin Pharmacol, 21, 267-270. 6. Koyoma H., Wada T., Nishizawa Y., Iwanaga T., Aoki Y., Terasawa T., Kosaki G., Yamamoto T., Wada A., 1977. Cyclophosphamide-induced ovarian failure and its therapeutic significance in patiens with breast cancer. Cancer, 39, 1403-1409. 7. Dönmez D., Yetim İ., 2018. Histological examination of the role of vitamin E in cyclophosphamide-induced testicular damage in rats. Anadolu Univ Bilim Teknol Derg, 7, 220-226. 8. Sampa G., Monomohon M., Ujijal Baran D., Rajkumar M., Jogendra Mohan D., Debidas G., 2001. Effect of human chorionic gonadotrophin co administration on ovarian steroidogenic and folliculogenic activities in cyclophosphamide treated albino rats. Reprod Toxicol, 15, 221-225. 9. Tripathi DN., Jena GB., 2009. Intervention of astaxanthin against cyclophosphamide-induced oxidative stress and DNA damage: a study in mice. Chem Biol Interact, 180, 398-406. 10. Wang X., Zhang J., Xu T., 2009. Cyclophosphamide-evoked heart failure involves pronounced co-suppression of cytoplasmic thioredoxin reductase activity and non-protein free thiol level. Eur J Heart Fail, 11, 154-162. 11. Caglayan C., Temel Y., Kandemir FM., Yildirim S., Kucukler S., 2018. Naringin protects against cyclophosphamide-induced hepatotoxicity and nephrotoxicity through modulation of oxidative stress, inflammation, apoptosis, autophagy, and DNA damage. Environ Sci Pollut R, 25, 20968-20984. 12. Temel Y., Kucukler S., Yıldırım S., Caglayan C., Kandemir FM., 2020. Protective effect of chrysin on cyclophosphamide-induced hepatotoxicity and nephrotoxicity via the inhibition of oxidative stress, inflammation, and apoptosis. N-S Arch Pharmacol, 393, 325-337. 13. 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. 14. Gelen V., Şengül 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. 15. Yaman Bülbül G., Mis L., Şengül E., Yıldırım S., Çelebi F., Çınar DA., 2018. Cyclophosphamide İle İndüklenmiş Ratlarda Karaciğer Enzimleri (AST, ALT, ALP) ve Histopatolojisi Üzerine Naringin’in Protektif Etkileri. Atatürk Üniversitesi Vet Bil Derg, 13, 182-190. 16. Dağ Y., Şengül E., Selçuk M., Yıldırım S., Çelebi F., Çınar DA., 2018. Ratlarda Cyclophosphamide ile İndüklenen Nefrotoksisitede Bazı Hematolojik Parametreler ve Böbreğin Histopatolojisi Üzerine Naringinin Protektif Etkileri. Atatürk Üniversitesi Vet Bil Derg, 13, 219-228. 17. Kwatra M., Kumar V., Jangra A., Mishra M., Ahmed S., Ghosh P., Khanam R., 2016. Ameliorative effect of naringin against doxorubicin-induced acute cardiac toxicity in rats. Pharm Biol, 54, 637-647. 18. Shanholtz C., 2011. Acute life-threatening toxicity of cancer treatment. Crit Care Clin, 7, 483-502. 19. Gelen V., Şengül E., Yildirim S., Çelebi F., Çinar DA., 2018. Ratlarda cyclophosphamide ile indüklenen hemorajik sistitte mesane kontraktilitesi ve histopatolojisi üzerine rutin’in etkileri. Atatürk Üniversitesi Vet Bil Derg, 13, 337-346. 20. Demirkaya M., 2012. Ratlarda siklofosfamid nedenli hepatoksisite üzerine karvakrol’ün koruyucu etkisi. Eskişehir Osmangazi Üniversitesi, Fen Bilimleri Enstitüsü, Türkiye. 21. Rezvanfar MA., Sadrkhanlou RA., Ahmadi A., Shojaei-Sadee H., 2008. Protection of cyclophosphamide induced toxicity in reproductive tract histology, sperm characteristic, and DNA damage by an herbal source; evidence for role of free-radical toxic stress. Hum Exp Toxicol, 27, 901-910. 22. Gore PR., Prajapati CP., Mahajan UB., Goyal SN., Belemkar S., Ojha S., Patil CR., 2016. Protective effect of thymoquinone against cyclophosphamide induced hemorragic cyctitis through inhibiting DNA damage upregralation of nrf2 expression. Int J Biol Sci, 12, 944-953. 23. Carino-Cortes R., Alvarez-Gonzalez I., Martino-Roaro L., Madrigal-Bujaidar E., 2010. Effect of naringin o the DNA damage induced by daunorubicin in mouse hepatocytes and cardiocytes. Biol Pharm Bull, 33, 697-701. 24. Kang YJ., Chen Y., Yu A., Voss-McCowan M., Epstein PN., 1997. Overexpression of metallothionein in the heart of transgenic mice suppresses doxorubicin cardiotoxicity. J Clin Invest, 100, 1501-1506. 25. Göktepe M., Günay M., 2014. Quercetin uygulamasının egzersiz, serbest radikal ve antioksidan enzim düzeyleri üzerine etkisi. Int J Sports Sci Coach, 2, 775-788. 26. Dong Q., Chen L., Lu Q., Sharma S., Li L., Morimoto S., Wang G., 2014. Quercetin attenuates doxorubicin cardiotoxicity by modulating Bmi-1 expression. Br J Pharmacol, 171, 4440-4454. 27. Aristatile B., Al‐Numair KS., Al‐Assaf AH., Veeramani C., Pugalendi KV., 2015. Protective effect of carvacrol on oxidative stress and cellular DNA damage induced by UVB irradiation in human peripheral lymphocytes. J Biochem Mol Toxic, 29, 497-507. 28. Bayramoglu G., 2007. Sıçanlarda siklofosfamid ile oluşturulmuş oksidatif strese karşı silimarinin olası koruyucu etkileri. Eskisehir Osmangazi Üniversitesi, Fen Bilimleri Enstitüsü, Türkiye. 29. 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. 30. Gelen V., Şengül 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. 31. 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. 32. Gedikli S., Şengül E. 2019. Ratlarda siklofosfamid ile indüklenen hepatotoksisite üzerine kuersetinin etkileri. Dicle Tıp Dergisi, 46, 41-50
Yıl 2020,
Cilt: 15 Sayı: 3, 231 - 236, 31.12.2020
Öz
In this study, it was aimed to investigate the protective effects of Naringin (NA) on antioxidants and free radicals in blood and serum samples in rats administered with cyclophosphamide (CYP). In our study, 40 male adult Sprague Dawley rats weighing about 200-250 g were used and 5 groups were formed with 8 rats in each group. The control group was given to intra-gastric (i.g.) saline (1 ml) for 10 days. The CYP group was given i.g. saline for 10 days and on the 10th day, a single dose of intraperitoneal (i.p.) CYP (200 mg/kg) was injected. NA50+CYP and NA100+CYP groups were administered NA at a dose of 50 and 100 mg/kg dissolved in saline for 10 days, respectively and and single dose CYP (200 mg/kg, i.p.) after NA last injection was injected. On the 12th day of the experiment, the rats were anesthetized with thiopental sodium (20 mg/kg) and intra cardiac blood samples were taken and they were decapitated. Total Antioxidant Status (TAS), Total Oxidant Status (TOS), Oxidative stress index (OSI) and 8-Hydroxydeoxyguanosine (8-OHdG) parameters in the blood and serum samples obtained from the rats were analyzed. It was determined that CYP increases oxidative stress in rats, suppresses antioxidants and causes DNA damage. It was determined that different doses of NA suppress oxidative stress caused by CYP, increase the amount of antioxidants and prevent DNA damage.
Anahtar Kelimeler
Kaynakça
- 1. Türker FA., Kayaalp SO., 2002. Kanser kemoterapisinin esasları ve antineoplastik ilaçlar. Rasyonel Tedavi Yönünden Tıbbi Farmakoloji. 380-415, Feryal Matbaacılık, Ankara. 2. Vollbracht C., Schneider B., Leendert V., Weiss G., Auerbach L., Beuth J., 2011. Intravenous vitamin C administration improves quality of life in breast cancer patients during chemo-/radiotherapy and aftercare: results of a retrospective, multicentre, epidemiological cohort study in Germany. In vivo, 25, 983-990. 3. Kintzel PE., 2001. Anticancer drug-induced kidney disorders. Incidence, prevention and management. Drug Safety, 24, 19-38. 4. Tripathi DN., Jena GB., 2008. Astaxanthin inhibits cytotoxic and genotoxic effects of cyclophosphamide in mice germ cells. Toxicology, 248, 96-103. 5. Al-Safi SA., Maddocks JL., 1986. Does 2-Mercaptoethane Sulphonate (mesna) Prevent Cyclophosphamide and Azathioprine Induced İmmunosuppression? In vitro studies. Br J Clin Pharmacol, 21, 267-270. 6. Koyoma H., Wada T., Nishizawa Y., Iwanaga T., Aoki Y., Terasawa T., Kosaki G., Yamamoto T., Wada A., 1977. Cyclophosphamide-induced ovarian failure and its therapeutic significance in patiens with breast cancer. Cancer, 39, 1403-1409. 7. Dönmez D., Yetim İ., 2018. Histological examination of the role of vitamin E in cyclophosphamide-induced testicular damage in rats. Anadolu Univ Bilim Teknol Derg, 7, 220-226. 8. Sampa G., Monomohon M., Ujijal Baran D., Rajkumar M., Jogendra Mohan D., Debidas G., 2001. Effect of human chorionic gonadotrophin co administration on ovarian steroidogenic and folliculogenic activities in cyclophosphamide treated albino rats. Reprod Toxicol, 15, 221-225. 9. Tripathi DN., Jena GB., 2009. Intervention of astaxanthin against cyclophosphamide-induced oxidative stress and DNA damage: a study in mice. Chem Biol Interact, 180, 398-406. 10. Wang X., Zhang J., Xu T., 2009. Cyclophosphamide-evoked heart failure involves pronounced co-suppression of cytoplasmic thioredoxin reductase activity and non-protein free thiol level. Eur J Heart Fail, 11, 154-162. 11. Caglayan C., Temel Y., Kandemir FM., Yildirim S., Kucukler S., 2018. Naringin protects against cyclophosphamide-induced hepatotoxicity and nephrotoxicity through modulation of oxidative stress, inflammation, apoptosis, autophagy, and DNA damage. Environ Sci Pollut R, 25, 20968-20984. 12. Temel Y., Kucukler S., Yıldırım S., Caglayan C., Kandemir FM., 2020. Protective effect of chrysin on cyclophosphamide-induced hepatotoxicity and nephrotoxicity via the inhibition of oxidative stress, inflammation, and apoptosis. N-S Arch Pharmacol, 393, 325-337. 13. 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. 14. Gelen V., Şengül 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. 15. Yaman Bülbül G., Mis L., Şengül E., Yıldırım S., Çelebi F., Çınar DA., 2018. Cyclophosphamide İle İndüklenmiş Ratlarda Karaciğer Enzimleri (AST, ALT, ALP) ve Histopatolojisi Üzerine Naringin’in Protektif Etkileri. Atatürk Üniversitesi Vet Bil Derg, 13, 182-190. 16. Dağ Y., Şengül E., Selçuk M., Yıldırım S., Çelebi F., Çınar DA., 2018. Ratlarda Cyclophosphamide ile İndüklenen Nefrotoksisitede Bazı Hematolojik Parametreler ve Böbreğin Histopatolojisi Üzerine Naringinin Protektif Etkileri. Atatürk Üniversitesi Vet Bil Derg, 13, 219-228. 17. Kwatra M., Kumar V., Jangra A., Mishra M., Ahmed S., Ghosh P., Khanam R., 2016. Ameliorative effect of naringin against doxorubicin-induced acute cardiac toxicity in rats. Pharm Biol, 54, 637-647. 18. Shanholtz C., 2011. Acute life-threatening toxicity of cancer treatment. Crit Care Clin, 7, 483-502. 19. Gelen V., Şengül E., Yildirim S., Çelebi F., Çinar DA., 2018. Ratlarda cyclophosphamide ile indüklenen hemorajik sistitte mesane kontraktilitesi ve histopatolojisi üzerine rutin’in etkileri. Atatürk Üniversitesi Vet Bil Derg, 13, 337-346. 20. Demirkaya M., 2012. Ratlarda siklofosfamid nedenli hepatoksisite üzerine karvakrol’ün koruyucu etkisi. Eskişehir Osmangazi Üniversitesi, Fen Bilimleri Enstitüsü, Türkiye. 21. Rezvanfar MA., Sadrkhanlou RA., Ahmadi A., Shojaei-Sadee H., 2008. Protection of cyclophosphamide induced toxicity in reproductive tract histology, sperm characteristic, and DNA damage by an herbal source; evidence for role of free-radical toxic stress. Hum Exp Toxicol, 27, 901-910. 22. Gore PR., Prajapati CP., Mahajan UB., Goyal SN., Belemkar S., Ojha S., Patil CR., 2016. Protective effect of thymoquinone against cyclophosphamide induced hemorragic cyctitis through inhibiting DNA damage upregralation of nrf2 expression. Int J Biol Sci, 12, 944-953. 23. Carino-Cortes R., Alvarez-Gonzalez I., Martino-Roaro L., Madrigal-Bujaidar E., 2010. Effect of naringin o the DNA damage induced by daunorubicin in mouse hepatocytes and cardiocytes. Biol Pharm Bull, 33, 697-701. 24. Kang YJ., Chen Y., Yu A., Voss-McCowan M., Epstein PN., 1997. Overexpression of metallothionein in the heart of transgenic mice suppresses doxorubicin cardiotoxicity. J Clin Invest, 100, 1501-1506. 25. Göktepe M., Günay M., 2014. Quercetin uygulamasının egzersiz, serbest radikal ve antioksidan enzim düzeyleri üzerine etkisi. Int J Sports Sci Coach, 2, 775-788. 26. Dong Q., Chen L., Lu Q., Sharma S., Li L., Morimoto S., Wang G., 2014. Quercetin attenuates doxorubicin cardiotoxicity by modulating Bmi-1 expression. Br J Pharmacol, 171, 4440-4454. 27. Aristatile B., Al‐Numair KS., Al‐Assaf AH., Veeramani C., Pugalendi KV., 2015. Protective effect of carvacrol on oxidative stress and cellular DNA damage induced by UVB irradiation in human peripheral lymphocytes. J Biochem Mol Toxic, 29, 497-507. 28. Bayramoglu G., 2007. Sıçanlarda siklofosfamid ile oluşturulmuş oksidatif strese karşı silimarinin olası koruyucu etkileri. Eskisehir Osmangazi Üniversitesi, Fen Bilimleri Enstitüsü, Türkiye. 29. 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. 30. Gelen V., Şengül 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. 31. 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. 32. Gedikli S., Şengül E. 2019. Ratlarda siklofosfamid ile indüklenen hepatotoksisite üzerine kuersetinin etkileri. Dicle Tıp Dergisi, 46, 41-50
Toplam 1 adet kaynakça vardır.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Konular | Sağlık Kurumları Yönetimi |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Yayımlanma Tarihi | 31 Aralık 2020 |
| Yayımlandığı Sayı | Yıl 2020 Cilt: 15 Sayı: 3 |