Agomelatin ve selenyum, deneysel İskemi Reperfüzyon hasarlı rat testis modelini nasıl etkiler?
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Dosyalar
Tarih
2023
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Necmettin Erbakan Üniversitesi Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/embargoedAccess
Özet
Agomelatin, literatürde antioksidatif, antiinflamatuar, antiapoptotik ve düz kaslarda miyorelaksan etkileri olduğu bildirilen bir melatonerjik reseptör analoğudur. Selenyum ise çok uzun zamandır antioksidan enzim aktivitesini arttırdığı kanıtlanmış olan, organizma için önemli bir eser elementtir. İskemi Reperfüzyon (İR) hasarı, doku ve organ düzeyinde geri dönüşü olmayan ciddi sağlık sorunlarına neden olabilir. Bu çalışmanın amacı, agomelatinin tek başına ve selenyumla birlikte testiküler İR hasarına karşı olası etkilerini araştırmaktır. 40 adet erkek rat randomize 5 gruba ayrılmıştır (n=8): Sham Operasyon (ShamOp), Agomelatin Kontrol (AgoK), İskemi Reperfüzyon (İR), Agomelatin + İskemi Reperfüzyon (AgoİR), Agomelatin + Selenyum + İskemi Reperfüzyon (AgoSeİR). ShamOp, sağlıklı grup; İR, hasar grubu; AgoK, proflaktik tedavi grubu; AgoİR ve AgoSeİR ise proflaktik tedavi + hasar grubudur. Agomelatin (20 mg/kg) ve selenyum (1,5 mg/kg), 1 mililitre (ml) distile su içerisinde vortekste karıştırılarak çözdürülmüş ve tedavi içeren tüm gruplara arka arkaya 14 gün boyunca intraperitoneal (i.p.) enjeksiyonla verilmiştir. İR hasarı, intramüsküler ketamin-xylazin (75 mg/kg-8 mg/kg) anestezisi altında, 720o cerrahi torsiyon (4 saat) / detrorsiyon (24 saat) uygulamasıyla indüklenmiştir. Histopatolojik incelemeler sol taraf testisler kullanılarak, Modifiye Johnsen Skorlaması ile yapılmıştır. Fizyolojik incelemeler ise sağ taraf testisler kullanılarak izole organ banyosu sisteminde gerçekleştirilmiştir. Histopatolojik verilerimizin istatistiksel analizine göre gruplarımız arasında anlamlı farklılıklar bulunmaktadır. Modifiye Johnsen skorları, AgoİR ve AgoSeİR gruplarında İR grubuna göre anlamlı düzeyde yükselmişti (p<0.001). Bunun yanında, AgoSeİR grubu, AgoİR grubundan da anlamlı ölçüde daha yüksek Johnsen sokruna sahipti (p<0.05). AgoK grubu AgoİR grubundan istatistiksel olarak anlamlı ölçüde yüksek Johnsen skoruna sahipti (p<0.05). Benzer şekilde, AgoK grubu AgoSeİR grubundan da yüksek Johnsen skoruna sahipti ancak aradaki fark anlamlı değildi (p>0.05). Johnsen skoru ShamOp grubunda, AgoİR ve AgoSeİR gruplarından daha yüksekti. Ancak aradaki farklılık AgoİR grubunda anlamlıyken (p<0.05) AgoSeİR grubunda değildi (p>0.05). Bununla birlikte, ShamOp grubu, AgoK grubuyla anlamlı bir farklılık göstermedi (p>0.05). Son olarak AgoK ve ShamOp grubları İR grubuna göre anlamlı düzeyde Johnsen skorlarına sahipti (p<0.001). İzole organ banyosu verilerimizin istatistiksel analizine göre gruplarımız arasında anlamlı bir farklılık bulunamamıştır (p>0.05). Ancak genlik parametrelerini grup içi zaman değerleri üzerinden analiz ettiğimizde AgoK, İR ve AgoİR gruplarında anlamlı azalmalar olduğunu belirledik (p<0.05). ShamOp grubu, anlamlı düzeyde olmasa da AgoK, İR ve AgoİR gruplarından daha iyi bir kasılma gücüne sahipti (p>0.05). Agomelatin cerrahi torsiyon/detorsiyonla indüklenmiş testiküler İR hasarına karşı, olasılıkla oksidatif stresi azaltarak, anlamlı düzeyde iyileştirici etki göstermiştir (p<0.001). Selenyum agomelatin ile beraber uygulandığında bu iyileştirici etkiyi anlamlı düzeyde arttırmaktadır (p<0.05). Bununla birlikte; ulaştığımız verilerin güvenilirliği açısından, sonuçlarımızın biyokimyasal parametreler üzerinden elde edilecek ilave kanıtlarla güçlendirilmesi gerektiğine inanıyoruz. Testis kapsülünün düz kas içeren tunica albuginea tabakasındaki kontraktilitenin spermi seminifer tübüllerden epididimise ileten güçlerden biri olduğu ve kapsülün kasılabilirliğindeki bir azalmanın inferiliteyi tetikleyebileceği bildirilmektedir. Deneysel verilerimizin analizine göre, agomelatinin testis kapsülü üzerindeki kısmi inhibitör etkisi ilacın doz bağımlı çalışmalarıyla desteklenmeye ihtiyaç duymaktadır.
Agomelatine is a melatonergic receptor analog that has been shown to be antioxidative, anti-inflammatory and anti-apoptotic in the literature, and myorelaxant effects on smooth muscles, although there are few studies demonstrating. Selenium is an important trace element for our organism, which has been proven to increase antioxidant enzyme activity for a very long time. Ischemia-Reperfusion (IR) injury can cause serious irreversible health problems at the tissue and organ level. The aim of this study is to investigate the possible effects of agomelatine alone and in combination with selenium against testicular IR injury. 40 male rats were randomly divided into 5 groups (n=8): Sham Operation (ShamOp), Agomelatine Control (AgoC), Ischemia-Reperfusion (IR), Agomelatine + Ischemia-Reperfusion (AgoIR), Agomelatine + Selenium + Ischemia-Reperfusion (AgoSeIR). ShamOp is healthy group; IR is injury group; AgoK is prophylactic treatment group; AgoIR and AgoSeIR are prophylactic treatment + injury groups. Agomelatine (20 mg/kg) and selenium (1.5 mg/kg) were dissolved in 1 milliliter (ml) of distilled water by mixing in the vortex and given to all treatment-containing groups by intraperitoneal (i.p.) injection for 14 consecutive days. IR injury was induced by intramuscular ketamine-xylazine (75 mg/kg-8 mg/kg) anesthesia under 720° surgical torsion (4 hours)/detrosion (24 hours). Histopathological examinations were performed with the Modified Johnsen Score using left-sided testicles. Physiological examinations were performed in an isolated organ bath system using right-sided testicles. According to the statistical analysis of our histopathological data, our groups have significant differences. Modified Johnsen scores were significantly higher in the AgoIR and AgoSeIR groups compared to the IR group (p<0.001). In addition, the AgoSeIR group had a significantly higher Johnsen score than the AgoIR group (p<0.05). The AgoC group had a statistically significantly higher Johnsen score than the AgoIR group (p<0.05). Similarly, the AgoC group had higher Johnsen scores than the AgoSeIR group, but the difference was not significant (p>0.05). The Johnsen score was higher in the ShamOp group than in the AgoIR and AgoSeIR groups. However, the difference was significant in the AgoIR group (p<0.05) but not in the AgoSeIR group (p>0.05). However, the ShamOp group did not differ significantly from the AgoC group (p>0.05). Finally, the AgoC and ShamOp groups had significant Johnsen scores compared to the IR group (p<0.001). No significant difference was found between our groups (p>0.05) based on the statistical analysis of our isolated organ bath data. However, when we analyzed the amplitude parameters over the within-group time values, we determined that there were significant decreases in the AgoC, IR and AgoIR groups (p<0.05). The ShamOp group had better contractile strength than the AgoC, IR and AgoIR groups, although not significantly (p>0.05). Agomelatine showed a significant therapeutic effect against surgical torsion/detorsion-induced testicular IR injury, possibly by reducing oxidative stress (p<0.001). When selenium is applied together with agomelatine, this curative effect increases significantly (p<0.05). Beyond that, we believe that our results should be strengthened with additional evidence from biochemical parameters in terms of the reliability of the data we have reached. It has been reported that the contractility in the smooth muscle-containing tunica albugine layer of the testis capsule is one of the forces that transmit the sperm from the seminiferous tubules to the epididymis, and a decrease in the contractility of the capsule may trigger infertility. The partial inhibitory effect of agomelatine on the testicular capsule needs to be supported by dose-dependent studies of the drug based on the analysis of our experimental data.
Agomelatine is a melatonergic receptor analog that has been shown to be antioxidative, anti-inflammatory and anti-apoptotic in the literature, and myorelaxant effects on smooth muscles, although there are few studies demonstrating. Selenium is an important trace element for our organism, which has been proven to increase antioxidant enzyme activity for a very long time. Ischemia-Reperfusion (IR) injury can cause serious irreversible health problems at the tissue and organ level. The aim of this study is to investigate the possible effects of agomelatine alone and in combination with selenium against testicular IR injury. 40 male rats were randomly divided into 5 groups (n=8): Sham Operation (ShamOp), Agomelatine Control (AgoC), Ischemia-Reperfusion (IR), Agomelatine + Ischemia-Reperfusion (AgoIR), Agomelatine + Selenium + Ischemia-Reperfusion (AgoSeIR). ShamOp is healthy group; IR is injury group; AgoK is prophylactic treatment group; AgoIR and AgoSeIR are prophylactic treatment + injury groups. Agomelatine (20 mg/kg) and selenium (1.5 mg/kg) were dissolved in 1 milliliter (ml) of distilled water by mixing in the vortex and given to all treatment-containing groups by intraperitoneal (i.p.) injection for 14 consecutive days. IR injury was induced by intramuscular ketamine-xylazine (75 mg/kg-8 mg/kg) anesthesia under 720° surgical torsion (4 hours)/detrosion (24 hours). Histopathological examinations were performed with the Modified Johnsen Score using left-sided testicles. Physiological examinations were performed in an isolated organ bath system using right-sided testicles. According to the statistical analysis of our histopathological data, our groups have significant differences. Modified Johnsen scores were significantly higher in the AgoIR and AgoSeIR groups compared to the IR group (p<0.001). In addition, the AgoSeIR group had a significantly higher Johnsen score than the AgoIR group (p<0.05). The AgoC group had a statistically significantly higher Johnsen score than the AgoIR group (p<0.05). Similarly, the AgoC group had higher Johnsen scores than the AgoSeIR group, but the difference was not significant (p>0.05). The Johnsen score was higher in the ShamOp group than in the AgoIR and AgoSeIR groups. However, the difference was significant in the AgoIR group (p<0.05) but not in the AgoSeIR group (p>0.05). However, the ShamOp group did not differ significantly from the AgoC group (p>0.05). Finally, the AgoC and ShamOp groups had significant Johnsen scores compared to the IR group (p<0.001). No significant difference was found between our groups (p>0.05) based on the statistical analysis of our isolated organ bath data. However, when we analyzed the amplitude parameters over the within-group time values, we determined that there were significant decreases in the AgoC, IR and AgoIR groups (p<0.05). The ShamOp group had better contractile strength than the AgoC, IR and AgoIR groups, although not significantly (p>0.05). Agomelatine showed a significant therapeutic effect against surgical torsion/detorsion-induced testicular IR injury, possibly by reducing oxidative stress (p<0.001). When selenium is applied together with agomelatine, this curative effect increases significantly (p<0.05). Beyond that, we believe that our results should be strengthened with additional evidence from biochemical parameters in terms of the reliability of the data we have reached. It has been reported that the contractility in the smooth muscle-containing tunica albugine layer of the testis capsule is one of the forces that transmit the sperm from the seminiferous tubules to the epididymis, and a decrease in the contractility of the capsule may trigger infertility. The partial inhibitory effect of agomelatine on the testicular capsule needs to be supported by dose-dependent studies of the drug based on the analysis of our experimental data.
Açıklama
Yüksek Lisans Tezi
Anahtar Kelimeler
Agomelatin, Selenyum, Testis, İskemi, Reperfüzyon, Agomelatine, Selenium, Testes, Ischemia, Reperfusion
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
İnal, A. T. (2023). Agomelatin ve selenyum, deneysel İskemi Reperfüzyon hasarlı rat testis modelini nasıl etkiler?. (Yayımlanmamış yüksek lisans tezi). Necmettin Erbakan Üniversitesi, Sağlık Bilimleri Enstitüsü Fizyoloji Anabilim Dalı, Konya.
