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Chinese Journal of Clinical Laboratory Management(Electronic Edition) ›› 2023, Vol. 11 ›› Issue (02): 65-70. doi: 10.3877/cma.j.issn.2095-5820.2023.02.001

• Original Article •     Next Articles

The effect and implication of inhibiting glycotoxicity pathway on mitochondrial dysfunction

Shaoying Li, Ying Wen, Cuiping Jia, Yuan Zhang(), Weihao Deng()   

  1. Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou Guangdong 510623, China
  • Received:2022-09-30 Online:2023-05-28 Published:2023-06-29
  • Contact: Yuan Zhang, Weihao Deng

Abstract:

Objective

To explore the effects of various glycotoxicity pathway inhibitors on cellular mitochondria, and provide better therapeutic strategy for the effective treatment of diabetic vascular complications.

Methods

In this study, we inhibited polyol, hexosamine, AGE and PKC pathway with epalrestat, azaserine, aminoguanidine, sotrastaurin, respectively in human umbilical vein endothelial cell (HUVEC) before and after high glucose treatment. The mitochondria ROS was determined by flow cytometry and mitochondrial division was observed by confocal laser microscopy.

Results

The mitochondrial ROS and fragmentation of HUVEC were significantly increased by high glucose stimulation. After high glucose incubation, the mitochondrial ROS level and fragmentation did not decrease significantly. However, pre-addition of glucose-toxic pathway inhibitors before hyperglucose stimulation can effectively reduce mitochondrial ROS levels and mitochondrial division in HUVEC.

Conclusions

Inhibition of the glucotoxic pathway after high glucose stimulation cannot effectively alleviate mitochondrial damage. When the glycotoxic pathway is inhibited in advance, mitochondrial damage can be effectively alleviated. It is expected to provide better therapeutic strategies for the effective treatment of diabetic vascular complications by clarifying the effects of various glucotoxic pathway inhibitors on cellular mitochondria.

Key words: endothelial cell, reactive oxygen species, diabetes mellitus, hyperglycemia

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