Publication: Timokinonun genetik absans epilepsisinin ve valproik asitin oluşturduğu testis hasarı üzerine olası iyileştirici etkisinin araştırılması
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Amaç: Bu çalışmanın amacı genetik absans epilepsinin ve tedavisinde kullanılan Valproik asitin testis dokusu ve sperm parametreleri üzerindeki etkisini göstermek ve timokinonu alternatif veya eş bir tedavi olarak değerlendirmektir. Gereç ve yöntem: 25 adet Wistar albino ve 25 adet GAERS suşu erkek sıçan kendi aralarında kontrol, sham, timokinon, VPA ve VPA+Timokinon olmak üzere beşer gruba ayrılmıştır. Alınan örneklerde sperm morfolojisi, genel testis morfolojisi, PCNA ve StAR immünohistokimyasal analizleri, oksidatif stres belirteçlerinin biyokimyasal analizi ve PCNA, StAR, ZO-1 ve apoptotik yolak proteinlerinin western blot analizleri gerçekleştirilmiştir. Bulgular: GAERS sıçanlarda apoptotik yolak proteinlerinin ekspresyonları, TOS (p<0,0001) ve OSI (p<0,0001) seviyeleri artarken, normal morfoloji sergileyen sperm miktarı (p<0,0001), testis histopatolojik skoru (P<0,001), PCNA (p<0,0001), StAR (p<0,001) ve ZO-1 (p<0,001), proteinlerinin ekspresyonları ve TAS (p<0,0001) seviyeleri azalmıştır. GAERS-VPA gruplarında normal morfoloji sergileyen sperm miktarı azalırken (P<0,05), testis histopatolojisinde GAERS-Kontrol gruplarına göre bir fark görülmemiştir. GAERS Timokinon/ VPA/ VPA+Timokinon gruplarında apoptoz proteinlerinin ekspresyonları azalırken, PCNA, StAR ve ZO-1 proteinlerinin ekspresyonları artmıştır. Sonuç: Genetik absans epilepsisi, sperm ve testis morfolojisini olumsuz etkilemiştir. PCNA, StAR ve ZO-1 proteinlerinin ekspresyonlarını azaltıp, oksidatif stresi ve apoptozu arttırmıştır. Timokinon, VPA ve VPA ile timokinonun eş zamanlı uygulaması testis ve sperm morfolojisini, PCNA, StAR ve ZO-1 proteinlerinin ekspresyonlarını, apoptoz ve oksidatif stresi olumlu etkilemiştir. Sonuçlarımız, timokinonun tek başına veya VPA ile eş zamanlı kullanımının absans epilepsinin sebep olduğu sperm ve testis hasarı üzerinde olumlu etkilerinin olabileceğini göstermektedir.
Objective: The aim of this study was to show the effect of genetic absence epilepsy and valproic acid used in the treatment of genetic absence epilepsy on testicular tissue and sperm parameters and to evaluate thymoquinone as an alternative or co-treatment against the damage caused by absence epilepsy and valproic acid on testicular and sperm parameters. Material and method: 25 wistar albino and 25 GAERS strain male rats were divided into five groups control, sham, thymoquinone, VPA and VPA+thymoquinone. Sperm and testicular morphology, PCNA and StAR immunohistochemical analysis, biochemical analysis of oxidative stress markers and western blot analysis of PCNA, StAR, ZO-1 and apoptotic pathway proteins were performed on the samples. Results: In GAERS rats, the expression of apoptotic proteins, TOS (p<0.0001) and OSI (p<0.0001) levels were increased, while the amount of sperm exhibiting normal morphology (p<0.0001), testicular histopathologic score (P<0.001), PCNA (p<0.0001), StAR (p<0.001) and ZO-1 (p<0.001), protein expressions and TAS (p<0.0001) levels were decreased. While the amount of sperm exhibiting normal morphology decreased in GAERS-VPA groups (P<0.05), there was no difference in testicular histopathology compared to GAERS-Control groups. In GAERS-Thymoquinone/ VPA/ VPA+Thymoquinone groups, the expression of apoptosis proteins decreased, while the expression of PCNA, StAR and ZO-1 proteins increased. Conclusion: Genetic absence epilepsy negatively affected sperm and testicular morphology. It decreased the expression of PCNA, StAR, ZO-1 proteins and increased oxidative stress and apoptosis. Administration of thymoquinone/ VPA/ VPA+thymoquinone positively affected testicular and sperm morphology, expression of PCNA, StAR and ZO-1 proteins, apoptosis and oxidative stress. Our results suggest that the use of thymoquinone/ VPA/ VPA+thymoquinone may have positive effects on absence epilepsy-induced sperm and testicular damage.
Objective: The aim of this study was to show the effect of genetic absence epilepsy and valproic acid used in the treatment of genetic absence epilepsy on testicular tissue and sperm parameters and to evaluate thymoquinone as an alternative or co-treatment against the damage caused by absence epilepsy and valproic acid on testicular and sperm parameters. Material and method: 25 wistar albino and 25 GAERS strain male rats were divided into five groups control, sham, thymoquinone, VPA and VPA+thymoquinone. Sperm and testicular morphology, PCNA and StAR immunohistochemical analysis, biochemical analysis of oxidative stress markers and western blot analysis of PCNA, StAR, ZO-1 and apoptotic pathway proteins were performed on the samples. Results: In GAERS rats, the expression of apoptotic proteins, TOS (p<0.0001) and OSI (p<0.0001) levels were increased, while the amount of sperm exhibiting normal morphology (p<0.0001), testicular histopathologic score (P<0.001), PCNA (p<0.0001), StAR (p<0.001) and ZO-1 (p<0.001), protein expressions and TAS (p<0.0001) levels were decreased. While the amount of sperm exhibiting normal morphology decreased in GAERS-VPA groups (P<0.05), there was no difference in testicular histopathology compared to GAERS-Control groups. In GAERS-Thymoquinone/ VPA/ VPA+Thymoquinone groups, the expression of apoptosis proteins decreased, while the expression of PCNA, StAR and ZO-1 proteins increased. Conclusion: Genetic absence epilepsy negatively affected sperm and testicular morphology. It decreased the expression of PCNA, StAR, ZO-1 proteins and increased oxidative stress and apoptosis. Administration of thymoquinone/ VPA/ VPA+thymoquinone positively affected testicular and sperm morphology, expression of PCNA, StAR and ZO-1 proteins, apoptosis and oxidative stress. Our results suggest that the use of thymoquinone/ VPA/ VPA+thymoquinone may have positive effects on absence epilepsy-induced sperm and testicular damage.