Health Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo, Egypt.
Biochemistry Division, Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-kom, Egypt.
Arch Biochem Biophys. 2023 May 15;740:109594. doi: 10.1016/j.abb.2023.109594. Epub 2023 Apr 5.
Cisplatin is one of the most significant anticancer. However, its use is associated with numerous toxicities especially nephrotoxicity. The main aim of this work was to examine the protective effect of Gallic acid (GA) and/or cerium oxide nanoparticles (CONPs) synthesized by gamma-irradiation on cisplatin-induced nephrotoxicity in rats. To do that, 48 adult male albino rats were separated into eight groups and received GA (100 mg/kg orally) and/or CONPs (15 mg/kg i. p.) for 10 days before injection with a single dose of cisplatin (7.5 mg/kg i. p.). The findings showed that cisplatin treatment impaired kidney functioning as shown by elevated serum levels of urea and creatinine. Additionally, the oxidative stress indicators (MDA and NO), levels of NF-kB, pro-inflammatory cytokines (IL1-and TNF-) and pro-apoptotic proteins (BAX and caspase-3) were raised after cisplatin injection, while levels of intrinsic anti-oxidants (CAT, SOD, and GSH) and anti-apoptotic protein (Bcl-2) were reduced. Moreover, renal toxicity was confirmed by alteration in normal histological architecture of the kidneys. On the other hand, pretreatment with CONPs and/or GA ameliorated cisplatin-induced nephrotoxicity as evidenced by improvement of renal function parameters and levels of oxidative stress, inflammatory and apoptotic markers in renal tissue along with the renal histopathological changes. This study clarifies how GA and CONPs protect against cisplatin-induced nephrotoxicity and demonstrates any potential synergism between them. Therefore, they can be considered as promising nephroprotective agents during chemotherapy.
顺铂是一种最重要的抗癌药物之一。然而，它的使用与许多毒性有关，尤其是肾毒性。这项工作的主要目的是研究没食子酸（GA）和/或通过γ辐照合成的氧化铈纳米粒子（CONPs）对顺铂诱导的大鼠肾毒性的保护作用。为此，将 48 只成年雄性白化大鼠分为 8 组，在注射顺铂（7.5mg/kg，ip）前，连续 10 天口服 GA（100mg/kg）和/或 CONPs（15mg/kg，ip）。研究结果表明，顺铂治疗会损害肾脏功能，表现为血清尿素和肌酐水平升高。此外，氧化应激指标（MDA 和 NO）、NF-kB 水平、促炎细胞因子（IL1-和 TNF-）和促凋亡蛋白（BAX 和 caspase-3）在注射顺铂后升高，而内源性抗氧化剂（CAT、SOD 和 GSH）和抗凋亡蛋白（Bcl-2）的水平降低。此外，肾脏毒性通过肾脏正常组织学结构的改变得到证实。另一方面，CONPs 和/或 GA 的预处理可改善顺铂诱导的肾毒性，表现为肾功能参数的改善以及氧化应激、炎症和凋亡标志物在肾组织中的水平，同时改善肾组织的组织病理学变化。本研究阐明了 GA 和 CONPs 如何防止顺铂引起的肾毒性，并表明它们之间可能存在协同作用。因此，它们可以被认为是化疗期间有前途的肾保护剂。
