Fatih Mehmet KANDEMİR, Sefa KÜÇÜKLER, Selim ÇOMAKLI, Selçuk ÖZDEMİR

Ratlarda Dosetaksel Kaynaklı Testis Toksisitesi Üzerine Silimarinin Etkileri: Biyokimyasal, Moleküler ve Histopatolojik Değerlendirme

Bu çalışmanın amacı; farklı kanser türlerinin tedavisinde yaygın olarak kullanılan dosetaksel (DTX)kaynaklı testis hasarına karşı doğal bir antioksidan olduğu bilinen silimarin (SLM)’in etkilerininaraştırılmasıdır. Çalışmada 35 adet erkek Spraque Dawley rat rastgele 5 gruba ayrıldı: Kontrolgrubu, DTX uygulanan grup, SLM 50 mg/kg uygulanan grup, DTX+SLM 25 mg/kg uygulanan grup,DTX+SLM 50 mg/kg uygulanan grup. DTX’in glutatyon peroksidaz (GPx), süperoksit dismutaz(SOD) ve katalaz (KAT) gibi antioksidan enzim aktivitelerini ve glutatyon (GSH) düzeylerini azaltıp,lipid peroksidasyonunu (LPO) artırarak oksidatif hasarı tetiklediği belirlendi. Ayrıca DTX ile kombineuygulanan SLM uygulamasının GSH seviyesini ve antioksidan enzim aktivitelerini arttırdığı, lipidperoksidasyonunu ise azalttığı ettiği tespit edildi. Çalışmada apoptozis belirteçlerinden kaspaz 8 ve9 seviyelerinin DTX grubunda gen ekspresyonu düzeyinde, kaspaz 3 seviyesinin iseimmunhistokimyasal incelemede arttığı, SLM uygulaması ile bu belirteçlerin düzeylerinde azalmaolduğu gözlendi. Sonuç olarak; DTX kaynaklı testis toksisitesinde SLM’in anti-oksidan ve antiapoptotik etki gösterdiği tespit edilmiş ve alternatif tıpta kullanılabilmesi için ileri düzey çalışmalarıngerekliliği ortaya konmuştur.

The Effects of Silymarin on Docetaxel Induced Testis Toxicity in Rats: Biochemical, Molecular and Histopathological Evaluation

The aim of the present study was to investigate the effects of the slymarin (SLM), which is known to be a natural antioxidant against testicular damaged induced by dosetaksel (DTX), which is commonly used in the treatment of various cancer types. In this study, 35 male Spraque Dawley rats were randomly divided into 5 groups: Control group, DTX-treated group, SLM -treated group (50 mg/kg), DTX+SLM -treated group (25 mg/kg), and DTX+SLM -treated group (50 mg/kg). It was determined that DTX induced oxidative damage by decreasing glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities and decreasing glutathione (GSH) levels and increasing lipid peroxidation. In addition, it was determined that SLM application increased GSH level and antioxidant enzyme activities and inhibited lipid peroxidation (LPO). In the study, it was observed that caspase 8 and 9 levels, one of the apoptosis markers, increased gene expression level in the DTX group and caspase 3 level increased in immunohistochemical examination, and decreased levels of these markers with SLM application. As a result; It has been determined that SLM shows anti-oxidant and anti-apoptotic effects in DTX-induced testicular toxicity and further studies are required for its use in alternative medicine.

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