Genetics and Cytology Department, National Research Center, Dokki, Egypt; Common First Year Deanship, King Saud University, Riyadh, Saudi Arabia.
Pharmacol Rep. 2018 Aug;70(4):804-811. doi: 10.1016/j.pharep.2018.02.009. Epub 2018 Feb 5.
Lead acetate (Led) and mercury chloride (Mer) represent important ecological and public health concerns due to their hazardous toxicities. Naturally found products play a vital role in chemopreventive agent innovation. The current study aimed to assess the modifying effect of garlic (Gar) and/or vitamin E (Vit E) against the half-maximal inhibitory concentration (IC50) Led and/or Mer-induced cytotoxic, genotoxic and apoptotic effects.
Human lung cells (WI-38) were pretreated with Gar and/or Vit E for 24h and then treated with Led and/or Mer either alone or with their combination for 24h. Cytotoxicity of Led and Mer and the viability of Gar and Vit E were assessed using MTT assay. The alkaline comet assay was used to assess DNA damage, whereas QRT-PCR was performed to evaluate p53, Bax, and Bcl2 mRNA-expression.
The results of this study showed that IC50 of Led was (732.72μg/mL) and for Mer was (885.83μg/mL), while cell viability effective dose for Gar was (300μg/mL) and for Vit E was (26,800μg/mL). Treating cells with the IC50-concentration of Led or Mer or their combination using half IC50 of both of them induced severe DNA-damage. Bax-expression was increased, while p53 and Bcl2-expressions were decreased. Pretreatment of cells with Gar and/or Vit E ameliorated the previous alternations.
Led and Mer can induce oxidative stress and change the expressions of apoptosis-related proteins in WI-38 cells. Gar and Vit E may be promising protective candidate agent against the toxic effect of heavy metals.
醋酸铅（Led）和氯化汞（Mer）因其毒性危害而成为重要的生态和公共卫生关注点。天然产物在化学预防剂创新中起着至关重要的作用。本研究旨在评估大蒜（Gar）和/或维生素 E（Vit E）对半数最大抑制浓度（IC50）的 Led 和/或 Mer 诱导的细胞毒性、遗传毒性和细胞凋亡作用的修饰作用。
用人肺细胞（WI-38）进行 Gar 和/或 Vit E 预处理 24 小时，然后单独或联合使用 Led 和/或 Mer 处理 24 小时。使用 MTT 测定法评估 Led 和 Mer 的细胞毒性以及 Gar 和 Vit E 的细胞活力。使用碱性彗星试验评估 DNA 损伤，而 QRT-PCR 则用于评估 p53、Bax 和 Bcl2 mRNA 表达。
本研究结果表明，Led 的 IC50 为（732.72μg/mL），Mer 的 IC50 为（885.83μg/mL），而 Gar 的细胞活力有效剂量为（300μg/mL），Vit E 的细胞活力有效剂量为（26,800μg/mL）。用 Led 或 Mer 的 IC50 浓度或它们的组合处理细胞，用它们的半 IC50 处理细胞，会引起严重的 DNA 损伤。Bax 表达增加，而 p53 和 Bcl2 表达减少。Gar 和/或 Vit E 预处理可改善上述变化。
Led 和 Mer 可诱导 WI-38 细胞氧化应激并改变凋亡相关蛋白的表达。Gar 和 Vit E 可能是重金属毒性的有前途的保护候选药物。
