Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, College of Animal Science, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China.
Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, College of Animal Science, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China.
Mol Med Rep. 2021 Oct;24(4). doi: 10.3892/mmr.2021.12352. Epub 2021 Aug 13.
Ferroptosis is a non‑apoptotic form of cell death that relies on iron and lipid peroxidation, which is associated with multiple pathological processes in several diseases. Erastin is a small molecule capable of initiating ferroptotic cell death in cancer cells, which has shown great potential for cancer therapy. However, the physiological and pathological role of erastin‑induced ferroptosis on healthy tissues has not been well characterized. The present study intraperitoneally injected erastin into healthy mice to detect the metabolic changes of several tissues of mice. Erastin injection induced typical characteristics of ferroptosis with higher level of serum iron and malondialdehyde and lower level of glutathione and glutathione peroxidase 4 protein. Erastin injection enhanced iron deposition in the brain, duodenum, kidney and spleen of mice. Erastin‑induced ferroptosis altered the blood index values, causing mild cerebral infarction of brain and enlarged glomerular volume of kidney. It also promoted the growth of duodenal epithelium with thicker, longer and denser villi in erastin‑treated mice. The findings provided evidence that erastin induced ferroptosis and caused pathological changes in healthy tissues of mice. This suggested that the anti‑tumor drug erastin was somewhat toxic to healthy tissues.
铁死亡是一种依赖于铁和脂质过氧化的非细胞凋亡形式的细胞死亡，与多种疾病的多种病理过程有关。恩拉霉素是一种能够在癌细胞中引发铁死亡的小分子，它在癌症治疗方面显示出巨大的潜力。然而，恩拉霉素诱导的铁死亡对健康组织的生理和病理作用尚未得到很好的描述。本研究通过腹腔注射恩拉霉素到健康小鼠体内，以检测小鼠几种组织的代谢变化。恩拉霉素注射诱导了典型的铁死亡特征，表现为血清铁和丙二醛水平升高，谷胱甘肽和谷胱甘肽过氧化物酶 4 蛋白水平降低。恩拉霉素注射增强了小鼠大脑、十二指肠、肾脏和脾脏的铁沉积。恩拉霉素诱导的铁死亡改变了血液指标值，导致大脑轻度脑梗死和肾脏肾小球体积增大。它还促进了十二指肠上皮细胞的生长，使恩拉霉素处理的小鼠的绒毛更厚、更长、更密集。这些发现为恩拉霉素诱导铁死亡并导致小鼠健康组织发生病理变化提供了证据。这表明抗肿瘤药物恩拉霉素对健康组织有一定的毒性。
