Protective Effects of Ferrostatin-1 on Liver and Kidney Tissues in Mice with Middle and Late Stages of Diabetes
10.13865/j.cnki.cjbmb.2024.04.1064
- VernacularTitle:铁抑素-1对糖尿病中晚期小鼠肝肾组织的保护作用
- Author:
Huan WANG
1
;
Ming-Xing ZHU
;
Zhi-Jing WU
;
Wei-Wen CHEN
;
Yan-Fang ZHENG
;
Ming-Qing HUANG
Author Information
1. 福建中医药大学药学院,福州 350122
- Keywords:
ferrostatin-1(Fer-1);
diabetic liver disease;
ferroptosis;
db/db mice;
HIF-1α/VEGF
- From:
Chinese Journal of Biochemistry and Molecular Biology
2024;40(6):848-856
- CountryChina
- Language:Chinese
-
Abstract:
Diabetes mellitus is a metabolic disease with high incidence and many complications,among which type 2 diabetes mellitus(T2DM)accounts for a large proportion.Current studies have shown that T2DM is accompanied by damage of liver,kidney,and other organs and its complications seriously en-danger human health.Ferroptosis generates many Reactive Oxygen Species(ROS)through the Fenton reaction,and the accumulation of ROS activates Hypoxia Inducible Factor-1(HIF-1α).As a result,the level of vascular endothelial growth factor(VEGF)is increased.Ferrostatin-1(Fer-1),a ferroptosis in-hibitor,has strong antioxidant capacity.Therefore,based on the hypoxia-inducible factor-1α/vascular endothelial growth factor(HIF-1α/VEGF)signaling pathway,we explored the therapeutic effect of Fer-1 on the liver and kidney tissues of diabetic mice.db/db mice(21～22 weeks old)were used as the model of diabetes mellitus.Ferroptosis inhibitor Fer-1 was used as the intervention drug.db/m mice served as the blank control group,and body weight and blood glucose were measured for 4 weeks.Food intake and water intake were recorded in each group.The levels of Alanine aminotransferase(ALT)and Aspartate aminotransferase(AST)in the serum were measured.ROS and Glutathione(GSH)activity in liver and kidney tissues and urinary protein content were measured.Liver and kidney tissue sections were stained with Hematoxylin-Eosin(HE),and the pathological morphology was observed under a light microscope.The protein levels of HIF-1α,VEGF,and glutathione peroxidase 4(GPX4)in liver and kidney tissues were detected by Western blot.In db/db mice,Fer-1(1 mg·kg-1,ig)could significantly reduce the a-mount of food and water intake,the levels of ALT and AST in serum,the ROS production in liver and kidney tissues,and the level of urine protein,but significantly increase the activity of GSH,thus improve the pathological conditions of liver and kidney.Fer-1 also significantly inhibited HIF-1α and VEGF pro-tein indexes and increased GPX4 protein levels in liver and kidney tissues.Although Fer-1 can not change the body weight and reduce blood glucose in diabetic mice,it can play a therapeutic role in the liver and kidney tissues of diabetic mice in the middle and late stages,and its mechanism may be related to HIF-1α/VEGF and GPX4.
