Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, 21511, Egypt.
Chemistry Department, Faculty of Science, Kafrelsheikh University, Kafrelsheikh, 33516, Egypt.
Environ Sci Pollut Res Int. 2022 Feb;29(6):8487-8502. doi: 10.1007/s11356-021-15834-x. Epub 2021 Sep 6.
Our previous study showed that dithiophenolate (DTP) and its chitosan nanoparticles (DTP-CSNPs) have abilities to bind with DNA helixes. So in this study, their lethal doses (LD) and therapeutic roles against rat liver injuries induced by carbon tetrachloride (CCl) were evaluated. The study focused on the determination of the markers of oxidative stress (OS) and apoptosis and compare the results with those of cisplatin treatment. The results revealed that LD values of DTP and DTP-CSNPs are 2187.5 and 1462.5 mg/kg, respectively. Treatment with DPT and DPT-CSNPs after CCl administration reduced liver injuries, induced by CCl, and improved liver functions and architecture through the reduction of OS and apoptosis. Where the oxidant marker was decreased with elevations of antioxidant markers. Also, there was an elevation in Bcl-2 value, with decreases in caspase-8, Bax, and Bax/Bcl-2 ratio. DPT-CSNPs treatment gave preferable results than those treated with DPT. Moreover, DTP and DPT-CSNPs treatment gave better results than cisplatin treatment. The administration of healthy rats with low doses of DTP and DTP-CSNPs for 14 days had no effect. Otherwise, the study on HepG2 cell line showed that DTP and DPT-CSNPs inhibited cell growth by arresting cells in the G2/M phase and inducing cell death. In conclusion, DTP and DTP-CSNPs have antiapoptotic and anti-oxidative stress toward hepatotoxicity induced by CCl. Moreover, DTP and DTP-CSNPs have anticancer activity against the HepG2 cell line. Generally, DTP-CSNPs are more effective than DTP. So, they can be used in the pharmacological fields, especially DTP-CSNPs.
我们之前的研究表明，二硫酚（DTP）及其壳聚糖纳米粒子（DTP-CSNP）具有与 DNA 螺旋结合的能力。因此，在这项研究中，评估了它们对四氯化碳（CCl）诱导的大鼠肝损伤的致死剂量（LD）和治疗作用。研究重点是确定氧化应激（OS）和细胞凋亡的标志物，并将结果与顺铂治疗进行比较。结果表明，DTP 和 DTP-CSNP 的 LD 值分别为 2187.5 和 1462.5 mg/kg。CCl 给药后用 DPT 和 DTP-CSNP 治疗可减轻 CCl 引起的肝损伤，改善肝功能和结构，减少 OS 和细胞凋亡。其中，氧化应激标志物降低，抗氧化标志物升高。此外，Bcl-2 值升高，caspase-8、Bax 和 Bax/Bcl-2 比值降低。DTP-CSNP 治疗的效果优于 DTP 治疗。此外，DTP 和 DTP-CSNP 治疗的效果优于顺铂治疗。健康大鼠连续 14 天低剂量给予 DTP 和 DTP-CSNP 无影响。相反，对 HepG2 细胞系的研究表明，DTP 和 DTP-CSNP 通过将细胞阻滞在 G2/M 期并诱导细胞死亡来抑制细胞生长。总之，DTP 和 DTP-CSNP 对 CCl 诱导的肝毒性具有抗凋亡和抗氧化应激作用。此外，DTP 和 DTP-CSNP 对 HepG2 细胞系具有抗癌活性。一般来说，DTP-CSNP 比 DTP 更有效。因此，它们可用于药理学领域，特别是 DTP-CSNP。
