In Vitro Genotoxic Effects of Ursodeoxycholic Acid in Human Peripheral Blood Lymphocytes

Abstract

Ursodeoxycholic acid (UDCA), the 7b epimer of chenodeoxycholic acid has been increasingly

used for the treatment of cholestatic liver diseases. In this study, it was aimed to determine the potential in vitro

genotoxic effects of ursodeoxycholic acid in human peripheral blood lymphocytes. The potential genotoxic and

cytotoxic effects of UDCA were investigated in vitro by using chromosome aberration and mitotic index assays.

Human peripheral blood lymphocytes were treated with 10, 50 and 100 μg/ml of UDCA for 24 and 48 hours. The

data were evaluated using one-way ANOVA (Post Hoc Analysis-LSD Test) test in the SPSS statistics program.

Statistical results showed that the applied doses of UDCA did not cause a significant increase in chromosome

aberration frequency, and also it did not cause a significant decrease in mitotic index when compared to the control

(p>0.05). The finding that UDCA does not cause an increase in chromosomal aberrations may be related to the

production of this substance physiologically as bile acid in the human body, even in trace amount. The fact that

there are many patients using UDCA increases the importance of findings obtained from this study.

Keywords

• Chromosome aberration test,Genotoxic effect,Human peripheral lymphocytes,Mitotic index,Ursodeoxycholic acid

Ursodeoksikolik Asit’in İnsan Periferal Kan Lenfositlerindeki in Vitro Genotoksik Etkisi

Abstract

Kenodeoksikolik asitin 7b epimeri olan ursodeoksikolik asit (UDKA), kolestatik karaciğer hastalıklarının

tedavilerinde artan bir şekilde kullanılmaktadır. Bu çalışmada, Ursodeoksikolik asitin, insan periferal kan

lenfositlerindeki in vitro sitotoksik ve genotoksik etkilerinin belirlenmesi hedeflendi. UDKA’nın potansiyel

genotoksik ve sitotoksik etkisi, kromozom aberasyon ve mitotik indeks testleri kullanılarak in vitro olarak araştırıldı.

İnsan peripheral kan lenfositleri, 24 ve 48 saat süreyle, 10, 50 ve 100 μg/ml UDKA ile muamele edildi. Veriler

SPSS istatistik programında, Tek Yönlü Anova (Post Hoc Analiz-LSD Test) testi ile analiz edildi. Elde edilen

istatistik sonuçları, kontrolle karşılaştırıldığında, uygulanan UDKA konsantrasyonlarının mitotik indeks değerlerini

düşürmediğini ve kromozom anomali frekanslarında da önemli bir artışa neden olmadığını göstermektedir (p>0.05).

UDKA’nın insan kromozomlarında anomalileri artırmaması bulgusu, bu maddenin az da olsa insan vücudunda

fizyolojik olarak üretilen bir safra asiti olması ile bağlantılı olabilir. UDKA’yı kullanan pek çok hasta olması, bu

çalışmadan elde ettiğimiz bulguların önemini artırmaktadır.

Keywords

• Genotoksik etki,İnsan periferal lenfositleri,Kromozom aberasyon testi,Mitotik indeks,Ursodeoksikolik asit

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