Department of Pathology, Cairo University, Giza, Egypt.
J Biochem Mol Toxicol. 2021 May;35(5):e22722. doi: 10.1002/jbt.22722. Epub 2021 Jan 23.
Cisplatin is a highly cytotoxic anticarcinogenic drug used to treat several kinds of solid tumors such as liver tumors. With the increase in the incidences associated with hepatic tumors and a lack of selectivity of cisplatin to cancer cells, it is important to explore new therapeutic strategies against them. The present study was designed to verify the ability of gold nanoparticles (GNPs) to improve the hepatotherapeutic effect of cisplatin against DENA-induced hepatic tumors and to declare its ability to reduce the renal toxicity induced by cisplatin. Forty male Wistar rats were divided into two groups (n = 20): Group (A)-negative control and group (B)-model of hepatocellular tumor induction. After 4 months, each group was subdivided into four subgroups as the following: Group (1) received normal saline, Group (2) was treated by cisplatin, Group (3) was treated by GNPs, Group (4) was treated by GNPs-cisplatin conjugates. Our results revealed a marked elevation in liver and kidney function tests and oxidant levels with a reduction in antioxidant levels in the DENA-administrated group. Remarkable histopathological alterations in the liver and kidney tissue sections were observed and confirmed by the overexpression of the immunohistochemical staining of placental glutathione S-transferase, Hep Par 1, and proliferating cell nuclear antigen. Noticeable improvements in all the measurable toxicological parameters were recorded in the group treated with either GNPs or GNPs-cisplatin conjugate not observed in the group treated with cisplatin. We can conclude that GNPs not only improve the distribution of cisplatin, targeting it to the site of tumors, but it also reduces the renal toxicity induced by cisplatin, which are the primary concerns in cancer therapy.
顺铂是一种高细胞毒性的抗癌药物,用于治疗多种实体肿瘤,如肝癌。随着与肝肿瘤相关的发病率的增加和顺铂对癌细胞的选择性不足,探索针对它们的新治疗策略非常重要。本研究旨在验证金纳米颗粒 (GNPs) 是否能够提高顺铂对 DENA 诱导的肝肿瘤的治疗效果,并证明其降低顺铂引起的肾毒性的能力。40 只雄性 Wistar 大鼠被分为两组(n = 20):组(A)-阴性对照和组(B)-肝细胞肿瘤诱导模型。4 个月后,每组又分为四个亚组:组(1)接受生理盐水,组(2)用顺铂治疗,组(3)用 GNPs 治疗,组(4)用 GNPs-顺铂缀合物治疗。我们的结果显示,DENA 给药组的肝功能和肾功能试验以及氧化水平显著升高,抗氧化水平降低。肝和肾组织切片的显著组织病理学改变通过胎盘谷胱甘肽 S-转移酶、Hep Par 1 和增殖细胞核抗原的免疫组织化学染色的过度表达得到证实。用 GNPs 或 GNPs-顺铂缀合物治疗的组中观察到所有可测量的毒理学参数都有明显改善,而用顺铂治疗的组中没有观察到这种情况。我们可以得出结论,GNPs 不仅可以提高顺铂的分布,将其靶向肿瘤部位,而且还可以降低顺铂引起的肾毒性,这是癌症治疗中的主要关注点。