Halofuginonun deneysel kolon kanserinde etkinliğinin belirlenmesi
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Dosyalar
Tarih
2016
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Selçuk Üniversitesi Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Kolon kanseri dünyada en fazla mortalite ve morbiditeye neden olan kanserlerden birisidir. Kolon kanseri tedavisinde cerrahi ve medikal tedavinin yanısıra alternatif tedavi seçenekleri de uygulanmaktadır. Halofuginon (HLF) uzun yıllardır veteriner alanda kriptosporidiozis ve koksidiozis tedavisinde kullanılan antiprotozoal ilaçtır. Son yıllarda yapılan çalışmalarda HLF'un antiproliferatif, antifibrotik, antianjiyogenik, antimetastatik, antiinflamatuar ve antioksidan etkilerinin olduğu belirtilmiştir. HLF'un antifibrotik, antiproliferatif, antianjiyogenik ve antiinflamatuar etkileri ile kolon kanseri oluşumunda faydalı olabileceği hipotez edildi. Bu çalışmanın amacı ratlarda azoksimetan ile indüklenen kolon kanseri üzerine HLF etkisini belirlemektir. Çalışmada kullanılan toplam 38 rat 4 gruba ayrıldı: Kontrol (KNT): (n:8), HLF (n:10, 0.4 mg/kg, PO, SID), kanser (KAN) (n:10, azoksimetan, 15 mg/kg, IP, haftada bir defa 2 hafta boyunca) ve KAN+HLF (n:10, azoksimetan, 15 mg/kg, IP, haftada bir defa 2 hafta boyunca+ HLF 0.4 mg/kg, PO, SID). Çalışma 18. hafta sonunda sonlandırıldı. Ratların kalbinden anestezi altında kan örnekleri alındıktan sonra ratlar servikal dislokasyon yöntemi ile ötenazi edildi. Çalışma boyunca gruplarda ölümler gözlendiği için istatistiksel değerlendirme her gruptan 7 rat üzerinde gerçekleştirildi. Aberrant kriptal foki (ACF)'yi belirlemek için ötenaziden hemen sonra kolon dokusu metilen mavisi ile boyandı. Hemogram değerleri (Akyuvar, alyuvar, platelet, hematokrit, hemoglobin) kan sayım cihazında ve biyokimyasal değerler (Alkalin fosfataz, total bilirubin, alanin aminotransferaz, aspartat aminotransferaz, gamma glutamil transferaz, total protein, albumin, kreatinin, kolesterol, trigliserid) otoanalizör cihazında belirlenirken, sitokinler (tümör nekrozis faktör (TNF)-α, interlöykin (IL)-2, IL-6, IL-10), tiyobarbitürik asit reaktif ürünleri ve 13,14-dihidro-15-keto-prostaglandin F2α değerleri ELISA okuyucusunda ölçüldü. HLF ve KNT gruplarında ACF gözlenmedi. ACF düzeyi KAN grubunda KAN+HLF grubuna göre ve TNF-α düzeyi KAN grubunda diğer grublara göre istatistiksel olarak önemli derecede yüksek bulundu (P<0.05). Ayrıca hemoglobin seviyesi, KAN+HLF grubunda KNT grubuna göre daha düşük iken (P<0.05), kolesterol seviyesi, HLF grubunda KAN+HLF grubuna göre, trigliserid seviyesi ise HLF grubunda KAN ve KAN+HLF grubuna göre daha yüksek bulundu (P<0.05). Ancak bu değişimler ratlar için belirtilen referans aralıkta belirlendi. Diğer parametrelerde ise herhangi bir değişiklik gözlenmedi. Sonuç olarak HLF'un kolon kanserinin ilerlemesini engelleyebileceği ve gelecekte kolon kanseri tedavisinde destek tedavi olarak kullanılabileceği ifade edilebilir.
Colon cancer is one cancer which causes the most mortality and morbidity in the world. Medical and surgical tecniques, as well some alternative therapies, are used in the therapy of colon cancer. Halofuginone (HLF) is widely used as antiprotozoon drug against to cryptosporidiosis and coccidiosis in veterinary medicine for a long time. Antiproliferative, antifibrotic, antiangionegic, antimetastatic, anti-inflammatuar and antioxidant effects of HLF have been reported in last years. In the current research, antiproliferative, antifibrotic, antiangiogenic and anti-inflammatuar effects of HLF have been considered; it has been hypothesized that HLF might inhibit tumorigenesis in experimentally induced colon cancer. Aim of this research is to investigate the effect of HLF on the progression of azoxymethane induced colon cancer in rats. Totally 38 male Wistar albino rats were divided 4 groups: Control (n:8, CNT), halofuginone (n:10, HLF, 0.4 mg/kg, PO, SID), cancer (n: 10, CAN, azoxymethane, 15 mg/kg, IP, once a week for two weeks) and CAN+HLF (n:10, azoxymethane, 15 mg/kg, IP, once a week for two weeks, HLF, 0.4 mg/kg, PO, SID). After 18 weeks, research was terminated. Blood samples were taken under anesthesia and all animals were sacrificed. During the experimental period, deaths were observed in groups and statistically evaluations of research were done from 7 rats of each group. Aberrant crypt foci (ACF) of colon were stain with Methylene blue. Hemogram values (white blood cell, red blood cell, platelet, hematocrit, hemoglobin) were determined with hemocell counter, biochemical values (Alkaline phosphatase, total bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, total protein, albumin, creatinine, cholesterol, triglyceride) were measured by autoanalyzer, whereas cytokines (Tumour necrosis factor (TNF)-α, interleukin (IL)-2, IL-6, IL-10), 13,14-dihydro-15-keto Prostaglandin F2α and Thiobarbituric Acid Reactive Substances levels were measured with ELISA reader. There was no observed any ACF in CNT and HLF group.Higher ACF was determined (P<0.05) in CAN group when compared to HLF+CAN group, in addition TNF-α level of cancer group was higher than all experimental groups. Hemoglobin level of CAN+HLF was lower (P<0.05) than CNT group, whereas cholesterol and triglyceride levels of HLF group were higher (P<0.05) than CAN and CAN+HLF. But these changes were within the referenge range of rats. No any changes were determimned in the other values. In conclusion, it may be stated that HLF inhibits tumor progression in colon cancer, and it may be evaluated as supportive drug in the treatment of colon cancer in the future.
Colon cancer is one cancer which causes the most mortality and morbidity in the world. Medical and surgical tecniques, as well some alternative therapies, are used in the therapy of colon cancer. Halofuginone (HLF) is widely used as antiprotozoon drug against to cryptosporidiosis and coccidiosis in veterinary medicine for a long time. Antiproliferative, antifibrotic, antiangionegic, antimetastatic, anti-inflammatuar and antioxidant effects of HLF have been reported in last years. In the current research, antiproliferative, antifibrotic, antiangiogenic and anti-inflammatuar effects of HLF have been considered; it has been hypothesized that HLF might inhibit tumorigenesis in experimentally induced colon cancer. Aim of this research is to investigate the effect of HLF on the progression of azoxymethane induced colon cancer in rats. Totally 38 male Wistar albino rats were divided 4 groups: Control (n:8, CNT), halofuginone (n:10, HLF, 0.4 mg/kg, PO, SID), cancer (n: 10, CAN, azoxymethane, 15 mg/kg, IP, once a week for two weeks) and CAN+HLF (n:10, azoxymethane, 15 mg/kg, IP, once a week for two weeks, HLF, 0.4 mg/kg, PO, SID). After 18 weeks, research was terminated. Blood samples were taken under anesthesia and all animals were sacrificed. During the experimental period, deaths were observed in groups and statistically evaluations of research were done from 7 rats of each group. Aberrant crypt foci (ACF) of colon were stain with Methylene blue. Hemogram values (white blood cell, red blood cell, platelet, hematocrit, hemoglobin) were determined with hemocell counter, biochemical values (Alkaline phosphatase, total bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, total protein, albumin, creatinine, cholesterol, triglyceride) were measured by autoanalyzer, whereas cytokines (Tumour necrosis factor (TNF)-α, interleukin (IL)-2, IL-6, IL-10), 13,14-dihydro-15-keto Prostaglandin F2α and Thiobarbituric Acid Reactive Substances levels were measured with ELISA reader. There was no observed any ACF in CNT and HLF group.Higher ACF was determined (P<0.05) in CAN group when compared to HLF+CAN group, in addition TNF-α level of cancer group was higher than all experimental groups. Hemoglobin level of CAN+HLF was lower (P<0.05) than CNT group, whereas cholesterol and triglyceride levels of HLF group were higher (P<0.05) than CAN and CAN+HLF. But these changes were within the referenge range of rats. No any changes were determimned in the other values. In conclusion, it may be stated that HLF inhibits tumor progression in colon cancer, and it may be evaluated as supportive drug in the treatment of colon cancer in the future.
Açıklama
Anahtar Kelimeler
Aberrant kriptal foki, Halofuginon, Kolon kanseri, Oksidatif durum, Sitokinler, Aberrant crypt foci, Colon cancer, Cytokines, Halofuginone, Oxidative status
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Çorum, O. (2016). Halofuginonun deneysel kolon kanserinde etkinliğinin belirlenmesi. Selçuk Üniversitesi, Yayımlanmış doktora tezi, Konya.
