Adnan Ayhancı, Özge Acar, Varol Şahintürk, Sibel Güneş, İlknur Kulcanay Şahin, Ahmet Musmul, Sema Uslu

SELENYUM SİKLOFOSFAMİD NEDENLİ HEPATOTOKSİSİTEYİ İYİLEŞTİREBİLİR

ÖZET: Siklofosfamid (CP)’in antitümör etkinliği dozu ile doğru orantılıdır. Bununla birlikte, yüksek dozlarda yaygın sitotoksisitelere neden olur. Selenyum (Se) yapısına katıldığı glutatyon peroksidaz gibi selenoproteinler yoluyla potansiyel besinsel bir antioksidan olarak biyolojik etkiler göstermektedir. Bu nedenle siklofosfamid nedenli hepatotoksisitede selenyumun olası koruyucu etkisinin araştırılması amaçlanmıştır. Toplam 42 adet erkek Spraque-Dawley sıçan 6 gruba (n=7) ayrıldı (kontrol, 150 mg/kg CP, 0.5 ve 1 mg/kg Se, CP+0.5 ve CP+1 mg/kg Se grupları). Se’un karaciğer toksisitesinde koruyucu etkisini belirlemek için serum alanin transaminaz (ALT), aspartat transaminaz (AST), alkalen fosfataz (ALP) ve laktat dehidrogenaz (LDH) seviyeleri belirlendi. Ayrıca karaciğer dokusu histolojik olarak da incelendi. CP uygulanan grupta serum ALT (%145), AST (%226), ALP (%88), ve LDH (%73) düzeyleri arttı. CP ile birlikte Se uygulanan gruplarda ALT, AST, ALP ve LDH düzeyleri azaldı (p<0.05). Histolojik incelemelerde de CP+Se gruplarında karaciğer doku hasarı önemli düzeyde azaldı. Sonuçlarımız selenyumun antioksidan etkilerinin olduğu ve siklofosfamid nedenli oksidatif hasarı ve çoklu organ toksisitelerini gidermede yararlı olabileceğini göstermiştir.ANAHTAR KELİMELER: Siklofosfamid, oksidatif stres, hepatotoksisite, selenyum, rat.SELENIUM AMELIORATES CYCLOPHOSPHAMIDE-INDUCED HEPATOTOXICITYABSTRACT: The antitumoral efficieny of CP is directly proportional to its administrated dose. However, high doses have a tendency to result in generalized cytotoxicity. Selenium (Se) is a potent nutritional antioxidant that carries out biological effects by its incorporation into selenoproteins, such as glutathione peroxidase. Therefore we aimed to investigate the possible protective effect of Se on CP-induced hepatotoxicity. A total of 42 male Spraque-Dawley rats were divided into 6 groups (n=7) (control, 150 mg/kg CP, 0.5 or 1 mg/kg Se and CP+0.5 and CP+1 mg/kg Se groups). In order to determine the protective effects of Se on liver toxicity, the levels of serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were determined. Also, the liver tissues were analysed histologically. Serum ALT (%145), AST (%226), ALP (%88), and LDH (%73) levels increased in CP administrated rats. In groups where CP and Se were given together ALT, AST, ALP, and LDH levels decreased (p<0.05). Histological analysis of liver tissue showed that tissue damage was significantly lower in CP+Se groups. Our results show that Se has antioxidant effects and that it may be useful to eliminate CP related oxidative damage. KEYWORDS: Cyclophosphamide, oxidative stress, hepatotoxicity, selenium, rat.

Anahtar Kelimeler:

Siklofosfamid, oksidatif stres, hepatotoksisite, selenyum

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