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Title: Kidney cell DNA damage caused by combined exposure to volatile anaesthetics and 1 Gy or 2 Gy radiotherapy dose in vivo.
Author: Benković V, Oršolić N, Knežević AH, Borojević N, Brozović G, Milić M.
Journal: Arh Hig Rada Toksikol; 2022 Apr 07; 73(1):62-70. PubMed ID: 35390237.
Abstract:
Patient immobilisation with volatile anaesthetics (VA) during radiotherapy is sometimes unavoidable. Although it is known that both VAs and ionising radiation can have nephrotoxic effects, there are no studies of their combined effects on DNA damage. The aim of this in vivo study was to address this gap by investigating whether 48 groups of healthy Swiss albino mice (totalling 240) would differ in kidney cell DNA damage response (alkaline comet assay) to isoflurane, sevoflurane, or halothane anaesthesia and exposure to 1 Gy or 2 Gy of ionising radiation. We took kidney cortex samples after 0, 2, 6, and 24 h of exposure and measured comet parameters: tail length and tail intensity. To quantify the efficiency of the cells to repair and re-join DNA strand breaks, we also calculated cellular DNA repair index. Exposure to either VA alone increased DNA damage, which was similar between sevoflurane and isoflurane, and the highest with halothane. In combined exposure (VA and irradiation with 1 Gy) DNA damage remained at similar levels for all time points or was even lower than damage caused by radiation alone. Halothane again demonstrated the highest damage. In combined exposure with irradiation of 2 Gy sevoflurane significantly elevated tail intensity over the first three time points, which decreased and was even lower on hour 24 than in samples exposed to the corresponding radiation dose alone. This study confirmed that volatile anaesthetics are capable of damaging DNA, while combined VA and 1 Gy or 2 Gy treatment did not have a synergistic damaging effect on DNA. Further studies on the mechanisms of action are needed to determine the extent of damage in kidney cells after longer periods of observation and how efficiently the cells can recover from exposure to single and multiple doses of volatile anaesthetics and radiotherapy. Imobilizacija bolesnika hlapljivim anesteticima (HA) tijekom radioterapije ponekad je neizbježna. Iako je poznato da i HA i ionizirajuće zračenje mogu imati nefrotoksične učinke, ne postoje istraživanja o njihovu kombiniranom učinku na oštećenje DNA bubrežnih stanica. Cilj ovog istraživanja in vivo na miševima soja Swiss albino bio je utvrditi oštećenje DNA stanica bubrega (alkalni komet-test) nakon anestezije izofluranom, sevofluranom ili halotanom i izlaganja ionizirajućem zračenju u dozama od 1 Gy ili 2 Gy. Uzorke bubrežnoga korteksa uzeli smo nakon 0, 2, 6 i 24 sata od izlaganja i izmjerili parametre komet-testa: duljinu repa i njegov intenzitet. Kako bismo kvantificirali učinkovitost staničnoga popravka, izračunali smo indeks popravka stanične DNA. Izloženost bilo kojem od testiranih anestetika povećalo je oštećenje DNA u odnosu na kontrolu, slično kod sevoflurana i izoflurana, a najveće kod halotana. U kombiniranom izlaganju HA-u i zračenju od 1 Gy, oštećenje DNA ostalo je na sličnim razinama u svim vremenskim točkama, ili je bilo čak niže od oštećenja prouzročenih samim zračenjem. Halotan je ponovno izazvao najveća oštećenja. U kombiniranom izlaganju sa zračenjem od 2 Gy sevofluran je značajno povećao intenzitet repa tijekom prvih triju vremenskih točaka, koji se smanjivao te je nakon 24 sata čak bio niži nego u uzorcima koji su bili izloženi samo zračenju. Potrebna su daljnja istraživanja mehanizma djelovanja kako bi se utvrdilo u kojoj mjeri oštećenja ostaju u bubrežnim stanicama nakon duljeg razdoblja, kao i koliko se učinkovito stanice mogu oporaviti nakon jednokratnog ili višekratnog izlaganja HA-u i zračenju.

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