Abstract

Cyclophosphamide (CYL) is a chemotherapeutic medication commonly used in managing various malignancies like breast cancer or leukemia. Though, CYL has been documented to induce lung toxicity. Mechanism of CYL toxicity is through oxidative stress and the release of damage-associated molecular patterns (DAMPs). Sesamol (SES) is a natural antioxidant isolated from Sesamum indicum and its effect against CYL-induced lung toxicity is not studied yet. This study aims to investigate whether SES could prevent any deleterious effects induced by CYL on lung using normal human lung cells, WI-38 cell line, without suppressing its efficacy. Cells were pretreated with SES and/or CYL for 24 h, then cell viability was estimated by MTS and trypan blue assays. The mode of cell death was determined by AO/EB staining. Additionally, caspase-3 level, oxidative stress, and inflammatory markers were evaluated by colorimetric and ELISA techniques. qRT-PCR was performed to evaluate RAGE, NF-κB, and Beclin-1 mRNA-expression. CYL-treated WI-38 cells developed a significantly increased cell death with enhanced oxidative and RAGE/NF-κb/Autophagy signaling, which were all attenuated after pretreatment with SES. Thus, we concluded that SES offered a protective role against CYL-induced lung injury via suppressing oxidative stress and RAGE/NF-κB/Autophagy signaling, which is a natural safe therapeutic option against CYL toxicities.

Graphic Abstract

中文翻译：

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芝麻酚通过抑制RAGE /NF-κB/自噬信号传导减轻环磷酰胺对正常人肺WI-38细胞的细胞毒作用

摘要

环磷酰胺（CYL）是一种化学治疗药物，通常用于处理各种恶性肿瘤，如乳腺癌或白血病。虽然，据报道CYL可以诱发肺毒性。CYL毒性的机制是通过氧化应激和损伤相关分子模式（DAMPs）的释放。芝麻酚（SES）是从印度芝麻中分离出来的天然抗氧化剂尚未研究其对共轭亚油酸诱导的肺毒性的作用。这项研究旨在调查SES是否可以使用正常的人肺细胞WI-38细胞系预防CYL诱导的对肺的任何有害作用，而不抑制其功效。用SES和/或CYL预处理细胞24小时，然后通过MTS和锥虫蓝测定法评估细胞活力。细胞死亡的方式通过AO / EB染色确定。另外，通过比色法和ELISA技术评估了caspase-3水平，氧化应激和炎性标志物。进行qRT-PCR评估RAGE，NF-κB和Beclin-1 mRNA的表达。经CYL处理的WI-38细胞的氧化和RAGE /NF-κb/自噬信号增强，细胞死亡显着增加，在用SES预处理后均减弱。从而，

图形摘要