Ahu PAKDEMİRLİ, Ruşen Koray EYİSON, Sermet SEZİGEN, Levent KENAR, Meral SARPER

SÜLFÜR MUSTARDIN GLUTATYON BAĞIMLI β-LİYAZ METABOLİTLERİNİN DÖRT FARKLI TİP IN VITRO HÜCRE KÜLTÜR MODELİ ÜZERİNDEKİ SİTOTOKSİK ETKİLERİNİN DEĞERLENDİRİLMESİ

Giriş: Sülfür mustard (SM) alkilleyici özelliği çok güçlü bir yakıcı ajan ve aynı zamanda yasaklanmış bir kimyasal harp maddesidir. SBMTE, MSMTESE ve SBMSE; SM’ın glutatyon bağımlı β-liyaz metabolitleridir. Bu çalışmanın amacı; β-liyaz metabolitlerinin sitotoksik etkilerini dört farklı tip in vitro insan hücre hattı üzerinde değerlendirmektir. Gereç ve Yöntem: İnsan retina pigment epitel hücre hattı, insan umbilikal ven endotel hücre hattı, insan oral keratinosit hücre hattı ve insan akciğer fibroblast hücre hattı beş farklı konsantrasyondaki (10, 50, 100, 500, and 1000 ng/mL) SBMTE, MSMTESE ve SBMSE’ye maruz bırakılmıştır. β-liyaz metabolitlerinin sitotoksik etkisi; maruziyetten 24, 48 ve 72 saat sonra yapılan MTT testlerinde yaşayan hücrelerin yüzdelerine göre tespit edilmiştir. Bulgular: SBMTE, MSMTESE ve SBMSE’nin farklı konsantrasyonlarının dört farklı hücre kültür modelinde 24, 48 ve 72 saatteki sitotoksik etkileri değerlendirildiğinde, yaşayan hücrelerin yüzdeleri anlamında istatistiki olarak anlamlı bir fark bulunmamıştır (p> 0.05). Sonuç: β-liyaz metabolitlerinin; SM’ın ana hedefi olan bu grup hücrelerde ortaya çıkan sitotoksik etkilerden doğrudan sorumlu olmadığı değerlendirilmektedir. Bulgularımız; SM maruziyeti sonrasında β-liyaz metabolitlerinin oksidan/antioksidan denge üzerindeki etkilerini anlamak için hayvan modellerinde kullanılabilir. Böylece SM kurbanlarının tedavisinde kullanılabilecek potansiyel antioksidan ajanların etkinlikleri değerlendirilebilir.

EVALUATION OF CYTOTOXICITY OF GLUTATHIONE DERIVED β-LYASE METABOLITES OF SULFUR MUSTARD ON FOUR DIFFERENT TYPES OF IN VITRO CELL CULTURE MODEL

Introduction: Sulfur mustard (SM) is an extremely alkylating vesicant agent and it is also a banned chemicalwarfare agent. SBMTE, MSMTESE, and SBMSE are glutathione derived β-lyase metabolites of SM. The aim ofthis study was to evaluate the cytotoxic effects of β-lyase metabolites on four different types of in vitro human celllines.Material and Methods: The human retinal pigmented epithelium cell line, human primary umbilical veinendothelial cell line, human oral keratinocytes cell line, and human lung fibroblast cell line were exposed to five different concentrations (10, 50, 100, 500, and 1000 ng/mL) of SBMTE, MSMTESE, and SBMSE. The cytotoxiceffects of β-lyase metabolites were determined at 24, 48, and 72 hours (h) after the exposure by MTT assay asviability rate “%”.Results: When the cytotoxic effects of different concentrations of SBMTE, MSMTESE, and SBMSE on four cellculture model at 24th, 48th, and 72th h were evaluated, there was no statistically significant difference found inmean of cell viability (p> 0.05).Conclusion: It is concluded that β-lyase metabolites are not directly responsible for the toxicity occurring in thesegroup of cells which are main targets of SM. Our findings could be used for understanding the effects of β-lyasemetabolites on oxidant/antioxidant balance after SM exposure in animal models. By this way, effectiveness ofpotential antioxidant agents for the treatment of victims of SM exposure could be evaluated.

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