Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan; School of Medicine, Fu Jen Catholic University, New Taipei 242, Taiwan.
Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 20224, Taiwan; Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung 202, Taiwan.
Mutat Res. 2024 Jan-Jun;828:111857. doi: 10.1016/j.mrfmmm.2024.111857. Epub 2024 Apr 3.
Inhaled anesthetics, such as isoflurane, may cause side effects, including short-term immunosuppression and DNA damage. In contrast, low molecular weight fucoidan (LMF), derived from brown seaweed, exhibits promising immunomodulatory effects. In this study, we determined the effect of isoflurane on telomeres and examined the potential of LMF to ameliorate the harmful effects of isoflurane. Male Lewis rats, the mouse lymphoma cell line YAC-1, and the human nature killer cell line NK-92 MI were exposed to isoflurane. The relative telomere length (T/S) ratio and mRNA expression were determined by quantitative PCR. The viability assay was used to assess cell viability. In vivo, 2% isoflurane exposure, which is a clinically relevant concentration, reduced telomere length, and correlated with exposure frequency and duration. Isoflurane concentrations above 2% shortened YAC-1 telomeres, with minimal impact on cell viability. LMF pre-treatment enhanced NK-92 MI cell survival resulting from isoflurane exposure and exerted superior telomere protection compared with LMF post-treatment. Furthermore, adding LMF during isoflurane exposure resulted in a significant increase in IFN-γ, TNF-α, and IL-10 mRNA compared with the untreated group. LMF protected against isoflurane-induced telomere shortening, enhanced NK cell viability, and modulated cytokine expression, thus mitigating postoperative immune suppression and risk of tumor metastasis.
吸入麻醉剂,如异氟醚,可能会引起副作用,包括短期免疫抑制和 DNA 损伤。相比之下,从褐藻中提取的低分子量褐藻糖胶(LMF)具有有希望的免疫调节作用。在这项研究中,我们确定了异氟醚对端粒的影响,并研究了 LMF 减轻异氟醚有害影响的潜力。雄性 Lewis 大鼠、小鼠淋巴瘤细胞系 YAC-1 和人自然杀伤细胞系 NK-92MI 暴露于异氟醚中。通过定量 PCR 测定相对端粒长度(T/S)比和 mRNA 表达。活力测定用于评估细胞活力。在体内,2%的异氟醚暴露,这是一个临床相关的浓度,会缩短端粒长度,并与暴露频率和持续时间相关。高于 2%的异氟醚浓度缩短 YAC-1 端粒,对细胞活力的影响最小。LMF 预处理增强了 NK-92MI 细胞在异氟醚暴露下的存活,并与 LMF 后处理相比具有更好的端粒保护作用。此外,与未处理组相比,在异氟醚暴露期间添加 LMF 会导致 IFN-γ、TNF-α 和 IL-10 mRNA 的显著增加。LMF 可防止异氟醚引起的端粒缩短,增强 NK 细胞活力,并调节细胞因子表达,从而减轻术后免疫抑制和肿瘤转移的风险。