Natural Products and Bioprospecting ( IF 4.8 ) Pub Date : 2020-11-20 , DOI: 10.1007/s13659-020-00286-6 Soad Z El-Emam 1
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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：
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 细胞的细胞毒性作用
抽象的
环磷酰胺 (CYL) 是一种化疗药物，常用于治疗乳腺癌或白血病等各种恶性肿瘤。然而，CYL 已被证明会引起肺毒性。 CYL 毒性的机制是通过氧化应激和损伤相关分子模式 (DAMP) 的释放。 Sesamol (SES) 是一种从芝麻中分离出来的天然抗氧化剂，其对 CYL 引起的肺毒性的作用尚未研究。本研究旨在研究 SES 是否可以使用正常人肺细胞 WI-38 细胞系来预防 CYL 对肺引起的任何有害影响，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和台盼蓝测定法评估细胞活力。通过AO/EB染色确定细胞死亡模式。此外，还通过比色法和 ELISA 技术评估了 caspase-3 水平、氧化应激和炎症标志物。进行 qRT-PCR 来评估 RAGE、NF-κB 和 Beclin-1 mRNA 表达。 CYL 处理的 WI-38 细胞的细胞死亡显着增加，氧化和 RAGE/NF-κb/自噬信号增强，这些信号在 SES 预处理后均减弱。因此，我们得出结论，SES 通过抑制氧化应激和 RAGE/NF-κB/自噬信号传导，对 CYL 诱导的肺损伤发挥保护作用，这是针对 CYL 毒性的天然安全治疗选择。
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