Is Dexmedetomidine Toxic on Kidney Cells (Hek-293)? Effects on Cytotoxicity, Reactive Oxygen Species (ROS) and Apoptosis

Year 2023, Volume: 5 Issue: 2, 372 - 9, 15.05.2023

Başak Pehlivan , Erdoğan Duran , Veli Fahri Pehlivan , İsmail Koyuncu

https://doi.org/10.37990/medr.1253117

Abstract

Aim: Dexmedetomidine; it is widely used in anesthesia and intensive care. We aimed to examine and compare the cytotoxic, reactive oxygen species (ROS) and apoptotic effects of dexmedetomidine on kidney cells (Hek-293) in vitro at two different high and cumulative doses.
Material and Methods: The half-maximum inhibitory concentration (IC50) dose of dexmedetomidine on Hek-293 cells was determined using the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) method. Then at two different doses of the drug; apoptotic effects were determined by Annexin-V Method, morphological examinations were determined by Acridine Orange Ethidium Bromide Method and intracellular ROS levels were determined by flow cytometry.
Results: The IC50 value of dexmedetomidine for Hek-293 cells was determined as 64.6559 μg/mL. Compared with the control group, doses of 50 and 100 µg/mL of dexmedetomidine tended to show cytotoxicity (p<0.05). dexmedetomidine was found to have a lower cytotoxic effect at a dose of 50 μg / mL than at a dose of 100 μg / mL (p<0.05).
Conclusion: In the study, it was determined that dexmedetomidine increased intracellular ROS more than clinical doses at two different concentrations on Hek-293 cells, cytotoxic doses caused an increase in ROS in cells and induced apoptosis. We think that the toxic effects of dexmedetomidine can be prevented with the data obtained from this study and further studies.

Keywords

Anesthesia, apoptosis, cytotoxicity, dexmedetomidine, human kidney cells (Hek-293), reactive oxygen species (ROS)

Supporting Institution

Harran University Scientific Research Projects Unit (HUBAK)

Project Number

19342

Thanks

The authors would like to express their sincere gratitude to the staff of Harran University Faculty of Medicine, Department of Biochemistry Laboratory and Hamza Erdoğdu for their support.

Deksmedetomidin Böbrek Hücreleri (Hek-293) Üzerinde Toksik midir ? Sitotoksisite, Reaktif Oksijen Türleri (ROS) ve Apoptoz Üzerine Etkileri

Abstract

Amaç: Deksmedetomidin; Anestezi ve yoğun bakımda yaygın olarak kullanılmaktadır. Amacımız Deksmedetomidinin böbrek hücreleri (Hek-293) üzerindeki sitotoksik, reaktif oksijen türleri (ROS) ve apoptotik etkilerini in vitro olarak iki farklı yüksek ve kümülatif dozda incelemek ve karşılaştırmak.
Gereç ve Yöntemler: Deksmedetomidinin Hek-293 hücreleri üzerindeki yarı maksimum inhibitör konsantrasyonu (IC50) dozu, 3-[4,5-dimetiltiazol-2il]-2,5-difeniltetrazolyum bromür (MTT) yöntemi kullanılarak belirlendi. Daha sonra ilacın iki farklı dozunda; apoptotik etkiler Annexin-V Yöntemi ile, morfolojik incelemeler Akridin Turuncu Ethidyum Bromür Yöntemi ile ve hücre içi reaktif oksijen türleri (ROS) seviyeleri akış sitometrisi ile belirlendi.
Bulgular: Deksmedetomidinin Hek-293 hücreleri için IC50 değeri 64,6559 μg/mL olarak belirlendi. Kontrol grubuyla karşılaştırıldığında, 50 ve 100 µg/mL deksmedetomidinin dozları sitotoksisite gösterme eğilimindeydi (p<0.05). deksmedetomidinin 50 μg/mL dozunda 100 μg/mL dozuna göre daha düşük sitotoksik etkiye sahip olduğu bulundu (p<0,05).
Sonuç: Bu çalışmada Hek-293 hücreleri üzerinde deksmedetomidin; İki farklı konsantrasyonda hücre içi ROS'u klinik dozlardan daha fazla artırarak toksik etkilere sahip olduğu bulunmuştur. Sitotoksik dozların hücrelerde ROS artışına neden olduğu ve apoptozu indüklediği belirlendi. Bu çalışmalardan elde edilen değerler ve ileride yapılacak çalışmaların sonuçları incelenerek bu ilaçların toksik etkilerinin önlenebileceği kanaatindeyiz.

Keywords

Anestezi, Apoptozis, Sitotoksite, Dexmedetomidine, İnsan Böbrek Epitel Hücreleri (Hek-293), Reaktif Oksijen Türleri (ROS)

Project Number

19342

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