Metotreksatın neden olduğu testis hasarına karşı curcuminin koruycu etkisinin incelenmesi
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Dosyalar
Tarih
2015
Yazarlar
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Yayıncı
Trakya Üniversitesi Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Metotreksat (MTX), kemik iliği, bağırsak mukozası, gonadlar gibi yüksek çoğalma gücüne sahip dokular üzerine yan etkileri olan ve yaygın kullanılan kemoterapötik bir ajandır. Bu çalışmada MTX’in yol açtığı testis hasarına karşı curcumin (CMN)’nin koruyucu etkisinin araştırılması amaçlandı. Onsekiz adet Wistar albino erkek sıçan herbirinde altı adet olacak şekilde 3 gruba ayrıldı. Kontrol grubuna intragastrik (ig.) yolla 14 gün boyunca dimetilsülfoksit (DMSO, CMN ile eşit hacimde); 2. gruba, intraperitoneal (ip.) olarak 11. gün tek doz MTX (20 mg/kg); 3. gruba, ig. yol ile 14 gün boyunca CMN (100 mg/kg/gün, DMSO içinde çözülerek) ve ek olarak yine 3. gruba, ip. olarak 11. günde tek doz MTX (20 mg/kg) verildi ve CMN son dozundan 24 saat sonra sakrifiye edilerek testis dokuları histolojik ve immünohistokimyasal olarak çalışıldı. İntrakardiak ponksiyon yoluyla kan örnekleri alınarak serumda total testosteron değerleri saptandı. Deneklerin vücut ve testis ağırlıkları ölçülerek testis ağırlığı/vücut ağırlığı oranı hesaplandı. Ek olarak, testis dokularında seminifer tübül çap ve epitel kalınlığı ile interstisyel alan genişliği ölçüldü. Hayvan ağırlıkları, serum testosteron seviyeleri, seminifer tübül çap ve epitel kalınlığının MTX grubunda kontrole göre anlamlı olarak azaldığı, testis ağırlıklarında ve testis ağırlığı/vücut ağırlığı oranında bir değişiklik olmadığı, histolojik olarak hasarlı seminifer tübül sayısının ve interstisyel alan genişliğinin anlamlı olarak arttığı görüldü. Buna ek olarak, NF-kB immünoreaktivitesi ve p38 MAPK immünopozitif hücre sayısında kontrole göre bir artış olduğu saptandı. Curcumin, MTX’in neden olduğu vücut ağırlıkları, serum testosteron seviyeleri, seminifer tübül çap ve epitel kalınlığındaki azalmayı önlerken, histolojik olarak hasarlı seminifer tübül sayısı ve interstisyel alan genişlik artışını anlamlı olarak azalttı. Bundan başka, artmış olan NF-kB immünoreaktivitesi ve f-p38 MAPK immünopozitif hücre sayısında azalmaya neden oldu. Sonuç olarak, CMN’nin MTX’in neden olduğu testis hasarını NF-kB ve p38 MAPK yolu üzerinden etki göstererek azaltabileceği kanısındayız.
Abstract
Methotraxate (MTX) is a chemotherapeutic agent which is commonly used and which has side effects on tissues with high proliferation potential such as bone marrow, intestinal mucosa and gonads. In this study, it is aimed to investigate the protective effects of curcumin (CMN) against to MTX-induced testis damage. Eighteen Wistar albino male rats were subdivided into three groups having each six rats in. To control group, during 14 days intragastric (ig.) dimethylsulfoxide (DMSO, with same volume of CMN); to 2. group, during 11 days, intraperitoneal(ip.) single dose MTX (20mg/kg); to 3. group, during 14 days, ig. CMN (100 mg/kg/day, dissolved in DMSO) and additionally to 3. group, during 11 days, ip. single dose MTX (20 mg/kg) were administered. Twenty four hours later than last dose of CMN, rats were sacrified and testis tissues were analysed for histological and immunohistochemical methods. Intracardiac blood samples were analysed for total testosteron value in serum. After weights of body and testis were measured, testis weight/body weight ratio was calculated. In addition, seminiferous tubules diameter, epithelium thickness and interstitial space diameter were measured. The weights of animals, serum testoteron levels and seminiferous tubules diameter and epithelial thickness were decreased significantly in MTX group in comparison with control group whereas, weights of testis and testis weights/body weights ratios were not changed. The number of histologically damaged seminiferous tubules and interstitial space diameter were increased significantly. In addition to this, immunoreactivity of NF-kB and pp38 MAPK immunopsitive cell numbers increased in MTX group comparing to control group. Curcumin protects the decrase on MTX-induced body weights, serum testosteron levels, seminiferous tubules diameter and epithelial thickness, whereas reduced the increase in histologically damaged seminiferous tubules number and interstitial space diameter. Moreover, it caused reduction in the increased immunoreactivity of NF-kB and numbers of pp38 MAPK immunopsitive cells. In conclusion, we are of the opinion that CMN could reduce MTX-induced testicular damage via the inhibition of NF-kB and p38 MAPK signaling pathway.
Abstract
Methotraxate (MTX) is a chemotherapeutic agent which is commonly used and which has side effects on tissues with high proliferation potential such as bone marrow, intestinal mucosa and gonads. In this study, it is aimed to investigate the protective effects of curcumin (CMN) against to MTX-induced testis damage. Eighteen Wistar albino male rats were subdivided into three groups having each six rats in. To control group, during 14 days intragastric (ig.) dimethylsulfoxide (DMSO, with same volume of CMN); to 2. group, during 11 days, intraperitoneal(ip.) single dose MTX (20mg/kg); to 3. group, during 14 days, ig. CMN (100 mg/kg/day, dissolved in DMSO) and additionally to 3. group, during 11 days, ip. single dose MTX (20 mg/kg) were administered. Twenty four hours later than last dose of CMN, rats were sacrified and testis tissues were analysed for histological and immunohistochemical methods. Intracardiac blood samples were analysed for total testosteron value in serum. After weights of body and testis were measured, testis weight/body weight ratio was calculated. In addition, seminiferous tubules diameter, epithelium thickness and interstitial space diameter were measured. The weights of animals, serum testoteron levels and seminiferous tubules diameter and epithelial thickness were decreased significantly in MTX group in comparison with control group whereas, weights of testis and testis weights/body weights ratios were not changed. The number of histologically damaged seminiferous tubules and interstitial space diameter were increased significantly. In addition to this, immunoreactivity of NF-kB and pp38 MAPK immunopsitive cell numbers increased in MTX group comparing to control group. Curcumin protects the decrase on MTX-induced body weights, serum testosteron levels, seminiferous tubules diameter and epithelial thickness, whereas reduced the increase in histologically damaged seminiferous tubules number and interstitial space diameter. Moreover, it caused reduction in the increased immunoreactivity of NF-kB and numbers of pp38 MAPK immunopsitive cells. In conclusion, we are of the opinion that CMN could reduce MTX-induced testicular damage via the inhibition of NF-kB and p38 MAPK signaling pathway.
Açıklama
Yüksek Lisans Tezi
Anahtar Kelimeler
Curcumin, p38, Metotreksat, Nükleer Faktör-Kappa B, Testis, Methotrexate, Nuclear Factor-Kappa B
