Increased oxidative stress caused by impaired mitophagy aggravated liver ischemia and reperfusion injury in diabetic mice.
J Diabetes Investig
; 14(1): 28-36, 2023 Jan.
Article
in En
| MEDLINE
| ID: mdl-36345578
ABSTRACT
AIMS/INTRODUCTION:
Emerging evidence has suggested the detrimental role of oxidative stress in aggravating ischemia and reperfusion (IR) injury in diabetic livers. Interplay between oxidative stress and mitophagy has been shown. However, the role and mechanism of mitophagy in regulating oxidative stress and IR injury in diabetic livers remain unclear. MATERIALS ANDMETHODS:
Wild-type and db/db (DB) mice were subjected to a partial warm liver IR model. Liver injury, oxidative stress, mitophagy and related molecular pathways were analyzed.RESULTS:
Here, we found that increased liver IR injury was observed in DB mice, as evidenced by higher levels of serum alanine aminotransferase and serum aspartate, worsened liver architecture damage and more hepatocellular death. DB mice also showed increased mitochondrial oxidative stress. Mitochondrial reactive oxygen species scavenge alleviated liver IR injury in DB mice. Mechanistic analysis showed that 5' adenosine monophosphate-activated protein kinase-mediated mitophagy was suppressed in DB mice post-IR. Pharmacological activation of 5' adenosine monophosphate-activated protein kinase by its agonist effectively restored mitophagy activation, leading to decreased mitochondrial oxidative stress and attenuated liver IR injury in DB mice.CONCLUSIONS:
Our findings showed that diabetes increased oxidative stress to exacerbate liver IR injury by impairing 5' adenosine monophosphate-activated protein kinase-mediated mitophagy. Strategies targeting oxidative stress and mitophagy might provide a promising approach to ameliorate liver IR injury in diabetes patients.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Reperfusion Injury
/
Diabetes Mellitus, Experimental
/
Liver Diseases
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Diabetes Investig
Year:
2023
Document type:
Article
Affiliation country:
China