Fatih Mehmet KANDEMİR, Emrah Hicazi AKSU, Sefa KÜÇÜKLER

Naringin'in Erkek Ratlarda Methotreaxte İndüklü Testis Apoptosisi ve Otofajisi Üzerine Oksidatif Stresi Azaltmak Yoluyla Koruyucu Etkisi

Bu çalışma erkek ratlarda methotrexate (MTX) indüklü testis hasarı üzerine Narinjin’in (NRG) muhtemel koruyucu etkisini araştırmak amacıyla yapılmıştır. Toplamda 35 adet erkek rat materyal olarak kullanılmıştır. Ratlar her grupta 7 adet olacak şekilde 5 gruba ayrılmıştır; Grup 1’e (Kontrol) çalışmanın ilk günü tek doz serum fizyolojik periton içi enjeksiyonu uygulanmıştır. Grup 2’ye (NRG 100) 7 gün boyunca oral yolla NRG (100 mg/kg CA/günlük) verilmiştir. Grup 3’e (MTX) çalışmanın ilk günü 20 mg/kg MTX peritoniçi enjeksiyon uygulanmıştır. Grup 4’e (NRG 50+MTX) çalışmanın ilk günü 20 mg/kg MTX uygulaması ile birlikte 7 gün boyunca 50 mg/kg/gün NRG oral yolla verilmiştir. Group 5’e (NRG 100+MTX): çalışmanın ilk günü 20 mg/kg MTX uygulaması ile birlikte 7 gün boyunca 50 mg/kg/gün NRG oral yolla verilmiştir. Sonuç olarak; MTX control grubuna kıyasla malondialdehit (MDA) seviyesini arttırmış ve glutatyon (GSH) seviyesi ile süperoksit dismutaz (SOD), katalaz (CAT) ve glutatyon perksidaz (GSH-Px) aktivitesini önemli derecede azaltmıştır. Diğer taraftan NRG (100 mg/kg) tedavisi MDA seviyesini azaltmış ve GSH seviyesi ile SOD, CAT, GSH-Px aktiviteleri MTX grubuna kıyasla artmıştır. NRG 50 tedavisi ise MTX grubuna kıyasla SOD aktivitesinde herhangi bir değişikliğe sebep olmamıştır. Aynı zamanda MTX uygulaması testis dokusunda kontrol grubuyla kıyaslandığında caspase-3 ve BCL-3 ekspresyon seviyelerini artırmıştır. Bununla birlikte NRG (hem 50 mg/kg hem de 1000 mg/kg dozda) tedavisinin MTX grubuna kıyasla caspase-3 ve BCL-3 ekspresyon seviyelerini anlamlı olarak azaltmıştır. Sonuç olarak NRG tedavisi (özellikle 100 mg/kg dozda) MTX indüklü testis toksisitesini azaltmıştır.

Protective Effect of Naringin on Methotrexate-Induced Testicular Apoptosis and Autophagy Via Reducing Oxidative Stress in Male Rats

In this study the possible protective effect of naringin (NRG) on methotrexate (MTX)–induceddamage on testes of rats was investigated. A total of 35 male rats were used as materials.Animals were divided into 5 groups, 7 rats in each; Group 1 (Control): A single dose injection ofphysiological saline was administered intraperitoneally on the first day. Group 2 (NRG 100): NRG(100 mg/kg b.w./ day) was given orally for 7 days. Group 3 (MTX): Single dose of 20 mg/kg of MTXwas given intraperitoneally on the first day. Group 4 (NRG 50+MTX) 50 mg/kg/day NRG was givenfor 7 days after a single intraperitoneal injection of 20 mg/kg MTX. Group 5 (NRG 100+MTX): 100mg/kg/day NRG was given for 7 days after a single intraperitoneal injection of 20 mg/kg MTX.As a results, MTX increased to malondialdehyde (MDA) levels and decreased glutathione (GSH)level and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px)activities when compared to control group. On the other hand, NRG (100 mg/kg) treatment causeddecreasing the MDA levels and increa the GSH levels and SOD, CAT, and GSH-Px activities whencompared to MTX alone group. NRG 50 mg/kg treatment did not increase SOD activity.Also, MTX treatment increased caspase-3 and B-cell lymphoma 3 protein (BCL-3) expressionlevels in testicular tissue when compared to control group. However, NRG (both at the dose of 50mg/kg and 100 mg/kg) treatment lightened significantly the testis caspase-3 and BCL-3 expressionlevels when compared to MTX alone group.In conclusion, NRG (especially at the dose of 100 mg/kg) treatment decreased MTX-inducedtesticular toxicity in male rats.

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