Mild Hypothermia Attenuates the Anesthetic Isoflurane-Induced Cytotoxicity.
Mild Hypothermia Attenuates the Anesthetic Isoflurane-Induced Cytotoxicity.
复制标题
轻度低温可减轻麻醉剂异氟烷引起的细胞毒性
DOI：
10.3389/fncel.2017.00015
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发表时间：
2017
影响因子：
5.3
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Li C;Dong Y;Chen D;Xie Z;Zhang Y
据报道，常用的吸入麻醉剂异氟烷可诱导DNA损伤和细胞毒性。然而，减少这些影响的方法在很大程度上仍有待确定。轻度低温具有神经保护作用。因此，我们着手评估亚低温是否可以保护异氟醚诱导的DNA损伤和细胞毒性。此外，我们通过评估亚低温对异氟醚诱导的ATP水平变化的影响来研究其潜在机制。H4人神经胶质瘤细胞用2%异氟烷处理3或6小时，伴随和不伴随轻度低温（35°C）。我们通过3-（4，5-二甲基噻唑-2-基）-2，5-二苯基四氮唑溴化物（MTT）和乳酸脱氢酶（LDH）测定来评估细胞活力。我们通过测量组蛋白H2 A变体X在Ser 139（γH2A.X）的磷酸化水平（DNA损伤的标志物）来确定DNA损伤。我们还测量了细胞中的ATP水平。在这里，我们表明，用2%异氟烷处理6小时诱导细胞毒性和DNA损伤。此外，用2%异氟烷处理3 h可降低ATP水平而不诱导细胞毒性。亚低温减弱异氟醚诱导的细胞毒性，DNA损伤和ATP减少的细胞。总之，这些数据表明，异氟烷诱导的ATP水平降低发生在异氟烷诱导的细胞毒性之前。异氟烷可通过降低ATP水平诱导DNA损伤并引起细胞毒性。亚低温可减轻异氟醚引起的ATP水平降低，从而减轻异氟醚引起的DNA损伤和细胞毒性。这些初步研究建立了一个系统，并将促进未来的研究麻醉神经毒性。
The commonly used inhalation anesthetic isoflurane has been reported to induce DNA damage and cytotoxicity. However, the methods to attenuate these effects remain largely to be determined. Mild hypothermia has neuroprotective effects. We therefore set out to assess whether mild hypothermia could protect the isoflurane-induced DNA damage and cytotoxicity. Moreover, we investigated the underlying mechanisms by assessing the effects of mild hypothermia on the isoflurane-induced changes in ATP levels. H4 human neuroglioma cells were treated with 2% isoflurane for 3 or 6 h with and without mild hypothermia (35°C). We assessed the cell viability by using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and lactate dehydrogenase (LDH) assay. We determined DNA damage by measuring levels of phosphorylation of the histone protein H2A variant X at Ser139 (γH2A.X), the marker of DNA damage. We also measured ATP levels in the cells. Here we showed that the treatment with 2% isoflurane for 6 h induced cytotoxicity and DNA damage in the cells. Moreover, the treatment with 2% isoflurane for 3 h decreased ATP levels without inducing cytotoxicity. Mild hypothermia attenuated the isoflurane-induced cytotoxicity, DNA damage, and ATP reduction in the cells. Taken together, these data suggest that the isoflurane-induced reduction in ATP levels occurred before the isoflurane-induced cytotoxicity. Isoflurane may induce DNA damage and cause cytotoxicity through reducing ATP levels. Mild hypothermia would ameliorate isoflurane-induced DNA damage and cytotoxicity by attenuating the isoflurane-induced reduction in ATP levels. These pilot studies have established a system and will promote the future investigations of anesthesia neurotoxicity.