Low-molecular-weight fucoidan increases telomere length and immunostimulatory effects on NK-92 cells following inhaled anesthetic injury

IF 1.5 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2024-01-01 DOI:10.1016/j.mrfmmm.2024.111857
Cheng-Hsi Chang , Pai-An Hwang
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Abstract

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.

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吸入麻醉损伤后,低分子量褐藻糖胶可增加端粒长度和对NK-92细胞的免疫刺激作用
异氟醚等吸入麻醉剂可能会产生副作用,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)具有良好的免疫调节作用。在这项研究中,我们确定了异氟烷对端粒的影响,并考察了 LMF 改善异氟烷有害影响的潜力。雄性 Lewis 大鼠、小鼠淋巴瘤细胞系 YAC-1 和人类自然杀伤细胞系 NK-92 MI 均暴露于异氟醚。通过定量 PCR 测定相对端粒长度(T/S)比和 mRNA 表达。活力测定法用于评估细胞活力。在体内,2%的异氟烷暴露(临床相关浓度)会减少端粒长度,并与暴露频率和持续时间相关。异氟醚浓度超过2%会缩短YAC-1端粒,但对细胞活力的影响很小。与LMF后处理相比,LMF前处理提高了异氟烷暴露导致的NK-92 MI细胞存活率,并发挥了更好的端粒保护作用。此外,与未处理组相比,在异氟烷暴露期间加入 LMF 会导致 IFN-γ、TNF-α 和 IL-10 mRNA 显著增加。LMF 可防止异氟烷诱导的端粒缩短,增强 NK 细胞的活力,调节细胞因子的表达,从而减轻术后免疫抑制和肿瘤转移的风险。
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来源期刊
CiteScore
4.90
自引率
0.00%
发文量
24
审稿时长
51 days
期刊介绍: Mutation Research (MR) provides a platform for publishing all aspects of DNA mutations and epimutations, from basic evolutionary aspects to translational applications in genetic and epigenetic diagnostics and therapy. Mutations are defined as all possible alterations in DNA sequence and sequence organization, from point mutations to genome structural variation, chromosomal aberrations and aneuploidy. Epimutations are defined as alterations in the epigenome, i.e., changes in DNA methylation, histone modification and small regulatory RNAs. MR publishes articles in the following areas: Of special interest are basic mechanisms through which DNA damage and mutations impact development and differentiation, stem cell biology and cell fate in general, including various forms of cell death and cellular senescence. The study of genome instability in human molecular epidemiology and in relation to complex phenotypes, such as human disease, is considered a growing area of importance. Mechanisms of (epi)mutation induction, for example, during DNA repair, replication or recombination; novel methods of (epi)mutation detection, with a focus on ultra-high-throughput sequencing. Landscape of somatic mutations and epimutations in cancer and aging. Role of de novo mutations in human disease and aging; mutations in population genomics. Interactions between mutations and epimutations. The role of epimutations in chromatin structure and function. Mitochondrial DNA mutations and their consequences in terms of human disease and aging. Novel ways to generate mutations and epimutations in cell lines and animal models.
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