Erastin‑induced ferroptosis causes physiological and pathological changes in healthy tissues of mice.

Abstract

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.