Clinical pharmacology department, faculty of medicine, Zagazig University, Zagazig, Sharqia, Egypt.
Pathology department, faculty of medicine, Zagazig University, Zagazig, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2020 Dec;393(12):2411-2425. doi: 10.1007/s00210-020-01946-7. Epub 2020 Jul 24.
Cisplatin and oxaliplatin are widely used anticancer drugs. Their use is restricted by their dose-limiting side effects: nephrotoxicity and neurotoxicity, respectively. Cerium oxide nanoparticles (CONPs) are promising antioxidant and anti-inflammatory agent. To test the possible ameliorative impact of CONPs on the toxic effect of cisplatin and oxaliplatin in male albino rats. Forty eight rats were divided into 6 groups: control group, CONPs group, cisplatin group, cisplatin and CONPs group, oxaliplatin group, and oxaliplatin and CONPs group. After 4 weeks, serum urea and creatinine, renal tissue level of interleukin 10 (IL10), and total antioxidant (TAO) were measured in control, CONPs, and cisplatin groups. The other kidney was used for histopathological and immunohistochemical studies. The right sciatic nerves and the lumbar spinal cord of rats from control, CONPs, and oxaliplatin groups were used for immunohistochemical evaluations of nitrotyrosine, myelin basic protein (MBP), and glial fibrillary acidic protein (GFAP). Cisplatin significantly increased serum urea and creatinine levels, significantly decreased the kidney level of IL10 and TAO with marked tubular necrosis, hemorrhage and renal damage. Also, it decreased IL10 immunohistochemical expression. CONPs significantly decreased the serum urea and creatinine level and increased IL10 and TAO with lower renal damage and strong IL10 expression compared with cisplatin group. Oxaliplatin significantly decreased MBP immunoreactivity and increased nitrotyrosine immunoreactivity. In the lumbar spinal cord, GFAP immunoreactivity was significantly increased. CONPs significantly increased MBP and decreased nitrotyrosine immunoreactivity. GFAP immunoreactivity was significantly decreased. CONPs ameliorated cisplatin and oxaliplatin primary toxicities through anti-inflammatory and antioxidant characteristics.
顺铂和奥沙利铂是广泛使用的抗癌药物。它们的使用受到其剂量限制的副作用的限制：分别是肾毒性和神经毒性。氧化铈纳米粒子（CONPs）是一种很有前途的抗氧化和抗炎剂。为了测试 CONPs 对顺铂和奥沙利铂在雄性白化大鼠中的毒性作用的可能改善作用。将 48 只大鼠分为 6 组：对照组、CONPs 组、顺铂组、顺铂和 CONPs 组、奥沙利铂组和奥沙利铂和 CONPs 组。4 周后，测量对照组、CONPs 组和顺铂组的血清尿素和肌酐、肾组织白细胞介素 10（IL10）水平和总抗氧化（TAO）。另一个肾脏用于组织病理学和免疫组织化学研究。控制组、CONPs 组和奥沙利铂组大鼠的右侧坐骨神经和腰脊髓用于免疫组织化学评估硝基酪氨酸、髓鞘碱性蛋白（MBP）和胶质纤维酸性蛋白（GFAP）。顺铂显著增加血清尿素和肌酐水平，显著降低肾脏 IL10 和 TAO 水平，并伴有明显的肾小管坏死、出血和肾损伤。此外，它还降低了 IL10 的免疫组织化学表达。与顺铂组相比，CONPs 组显著降低了血清尿素和肌酐水平，增加了 IL10 和 TAO，肾损伤较低，IL10 表达较强。奥沙利铂显著降低 MBP 免疫反应性，增加硝基酪氨酸免疫反应性。在腰椎脊髓中，GFAP 免疫反应性显著增加。CONPs 显著增加 MBP，减少硝基酪氨酸免疫反应性，GFAP 免疫反应性显著降低。CONPs 通过抗炎和抗氧化特性改善顺铂和奥沙利铂的原发性毒性。
