Caveolin-1 alleviates acetaminophen-induced vascular oxidative stress and inflammation in non-alcoholic fatty liver disease.
Free Radic Biol Med
; 195: 245-257, 2023 02 01.
Article
in En
| MEDLINE
| ID: mdl-36596386
ABSTRACT
Acetaminophen (APAP) is one of the most widely used drugs in the world. The literature shows that excessive or long-term use of APAP can lead to increased cardiovascular dysfunction. An acute increase in angiotensin â
¡ (Ang â
¡) caused by APAP use in fatty liver disease may increase the risk and severity of vascular injury. However, the underlying mechanism remains unclear. Caveolin-1 (CAV1) is a broad-spectrum kinase inhibitor that significantly determines endothelial function. This study aimed to observe the effects of APAP on the vasculature in non-alcoholic fatty liver disease (NAFLD) and to determine whether CAV1 could alleviate vascular oxidative stress and inflammation by targeting Ang â
¡ or its downstream pathways. In this study, 7-week-old C57BL/6 male mice (18-20 g) were administered APAP by gavage after eight weeks of a high-fat diet. Any resulting vascular oxidative stress and inflammation were assessed. Levels of Ang â
¡, CAV1, and other related proteins were measured using ELISA and western blotting. In APAP-treated NAFLD mice, CAV1 expression was downregulated and Ang â
¡ expression was upregulated compared to normal APAP-treated mice. In vitro, HUVECs were incubated with Ang â
¡ (300 nM) for 48 h. Overexpression of CAV1 in HUVECs attenuated Ang â
¡-induced oxidative stress and inflammation and downregulated the expression of Protein kinase C (PKC) and p-P38/P38. After intervention with CAV1-siRNA, immunofluorescence results showed that the fluorescence intensity of PKC on mitochondria was further increased, and flow cytometry results showed that the mitochondrial membrane potential increased. PKC inhibitors alleviated Ang â
¡-induced endothelial injury. In conclusion, our findings confirmed that CAV1 exerts a protective effect against vascular injury by inhibiting oxidative stress and inflammation through the PKC/MAPK pathway. Therefore, restoration of CAV1 may have clinical benefits in reducing APAP-induced vascular damage in NAFLD patients.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Caveolin 1
/
Chemical and Drug Induced Liver Injury
/
Vascular System Injuries
/
Non-alcoholic Fatty Liver Disease
Limits:
Animals
Language:
En
Journal:
Free Radic Biol Med
Journal subject:
BIOQUIMICA
/
MEDICINA
Year:
2023
Document type:
Article