Turkiye Klinikleri Journal of Anesthesiology Reanimation

.: ORIGINAL RESEARCH
Effect of Liver Ischemia-Reperfusion Injury on Genotoxicity in Rabbits: Experimental Study
Tavşanlarda Karaciğer İskemi-Reperfüzyon Hasarının Genotoksisite Üzerine Etkisi: Deneysel Çalışma
Meltem BEKTAŞa , Ela KADIOĞLUa , Mert NAKİPb , Mehmet ÇAKIRCAa , Ayşe ÖZCANc , Çetin KAYMAKc
aDepartment of Anesthesiology and Reanimation, Health Sciences University Ankara Training and Research Hospital, Ankara, Türkiye
bDepartment of Toxicology, Gazi University Faculty of Pharmacy, Ankara, Türkiye
cDepartment of Anesthesiology and Reanimation, Health Sciences University Ankara Health Application and Research Center, Ankara, Türkiye
Turkiye Klinikleri J Anest Reanim. 2023;21(2):47-52
doi: 10.5336/anesthe.2023-96522
Article Language: EN
Full Text
ABSTRACT
 Objective: Ischemia-reperfusion (I-R) injury is defined as the paradoxical exacerbation of cellular dysfunction and death following restoration of blood flow to ischemic tissues. In our study, it was aimed to examine the potential DNA injury effects of liver IR injury with an experimental animal model. Material and Methods: In the study, modeling was done with seven male New Zealand rabbits. Blood samples were taken before the experimental IR model, 30 minutes after ischemia, and 60 minutes after reperfusion. The DNA damage in the blood of the rabbits was measured using Tail Length, Intensity, and Moment techniques. Statistical significance was determined using one-way analysis of variance (ANOVA) and Tukey's post hoc test. Results: There are significant differences between control-ischemia, control-reperfusion and I-R groups in all 3 measurements. Tail length; increased by 51.84%, 54.16% after ischemia and reperfusion, respectively. Tail length increased by 134.09% between control and reperfusion. Similarly, tail density and tail moment were increased by 78.95% (after ischemia), 77.96% (after reperfusion), 85.54% (after ischemia), 165.52% (after reperfusion) respectively. Conclusion: Tissue blood flow disruption is known to occur tissue hypoxia that triggers anaerobic respiration. Restoring blood flow to a hypoxic-tissue results in an increase in reactive oxygen species production. Literature stated I/R-related DNA damage may result from the formation of oxygen radicals during the reperfusion period. Moreover, it induces oxidative damage and exceeds the antioxidative capacity of circulating leukocytes, leading to DNA damage. In our study, DNA lesions characteristic of DNA damage mediated by free radicals were detected at a significantly increased level during reperfusion.

Keywords: Comet assay; DNA damage; ischemia; reperfusion injury; rabbits
ÖZET
 Amaç: İskemi-reperfüzyon (I-R) hasarı, iskemik dokulara kan akışının yeniden sağlanmasını takiben, hücresel işlev bozukluğunun ve ölümün paradoksal alevlenmesi olarak tanımlanır. Çalışmamızda, deneysel hayvan modeli ile karaciğer I-R hasarının potansiyel DNA hasarı etkilerinin incelenmesi amaçlanmıştır. Gereç ve Yöntemler: Çalışmada, 7 adet erkek Yeni Zelanda tavşanı ile modelleme yapılmıştır. Deneysel I-R modeli öncesi, iskemi sonrası 30. dk ve reperfüzyon sağlandıktan 60 dk sonra kan örnekleri alınmıştır. Tavşanların kanlarındaki DNA hasarı Kuyruk Uzunluğu, Yoğunluk ve Moment teknikleri kullanılarak ölçüldü. İstatistiksel anlamlılık, tek yönlü varyans analizi (ANOVA) ve Tukey'in post hoc testi kullanılarak belirlendi. Bulgular: Her 3 ölçümde hem kontrol-iskemi hem kontrol-reperfüzyon hem de I/R grupları arasında anlamlı farklılıklar vardır. Kuyruk uzunluğu; iskemi ve reperfüzyon sonrasında sırasıyla %51,84 ve %54,16 artmıştır. Kuyruk uzunluğu, kontrol ve reperfüzyon arasında %134,09 artmıştır. Benzer şekilde, kuyruk yoğunluğu ve kuyruk momenti iskemi ve reperfüzyon sonrası sırasıyla %78,95 (iskemi sonrası), %77,96 (reperfüzyon sonrası) ve %85,54 (iskemi sonrası), %165,52 (reperfüzyon sonrası) artış göstermiştir. Sonuç: Doku kan akımının bozulmasının anaerobik solunumu tetikleyen doku hipoksisi oluşturduğu bilinmektedir. Hipoksik bir dokuya kan akışının yeniden sağlanması reaktif oksijen türlerinin üretiminde artışa neden olur. Literatürde, I-R ile ilişkili DNA hasarı, reperfüzyon periyodu sırasında oksijen radikallerinin oluşumundan kaynaklanabilir. Ayrıca oksidatif hasara neden olur ve dolaşımdaki lökositlerin antioksidan kapasitesini aşarak DNA hasarına yol açar. Çalışmamızda, serbest radikallerin aracılık ettiği DNA hasarının özelliği olan DNA lezyonlarının, reperfüzyon sırasında önemli ölçüde arttığı tespit edilmiştir.

Anahtar Kelimeler: Comet assay; DNA hasarı; iskemi; reperfüzyon hasarı; tavşanlar
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