Cocaine-derived hippuric acid activates mtDNA-STING signaling in alcoholic liver disease: Implications for alcohol and cocaine co-abuse.
Cell Biol Toxicol
; 40(1): 71, 2024 Aug 16.
Article
en En
| MEDLINE
| ID: mdl-39147926
ABSTRACT
The simultaneous abuse of alcohol-cocaine is known to cause stronger and more unpredictable cellular damage in the liver, heart, and brain. However, the mechanistic crosstalk between cocaine and alcohol in liver injury remains unclear. The findings revealed cocaine-induced liver injury and inflammation in both marmosets and mice. Of note, co-administration of cocaine and ethanol in mice causes more severe liver damage than individual treatment. The metabolomic analysis confirmed that hippuric acid (HA) is the most abundant metabolite in marmoset serum after cocaine consumption and that is formed in primary marmoset hepatocytes. HA, a metabolite of cocaine, increases mitochondrial DNA leakage and subsequently increases the production of proinflammatory factors via STING signaling in Kupffer cells (KCs). In addition, conditioned media of cocaine-treated KC induced hepatocellular necrosis via alcohol-induced TNFR1. Finally, disruption of STING signaling in vivo ameliorated co-administration of alcohol- and cocaine-induced liver damage and inflammation. These findings postulate intervention of HA-STING-TNFR1 axis as a novel strategy for treatment of alcohol- and cocaine-induced excessive liver damage.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
ADN Mitocondrial
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Transducción de Señal
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Cocaína
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Hipuratos
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Hepatopatías Alcohólicas
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Proteínas de la Membrana
Límite:
Animals
Idioma:
En
Revista:
Cell Biol Toxicol
Asunto de la revista:
TOXICOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Corea del Sur