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Assessment of Glutamine as a Fuel Source for Alveolar Macrophages Exposed to Chronic Ethanol Using an Extracellular Flux Bioanalyzer
Published on: November 15, 2024
Subchronic Alcohol Exposure Exacerbates Acetaminophen-Induced Acute Liver Injury via Macrophage-Mediated Inflammation
Qingyang Zhang1, Hu Liu1, Weigao Zhang1
1School of Environmental and Biological Engineering, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing 210094, China, njust.edu.cn.
None:
Alcohol use is a major coexposure in patients taking acetaminophen (APAP), yet how subchronic alcohol exposure reshapes hepatic vulnerability to APAP remains incompletely defined. In this study, we examined the effects of chronic alcohol intake on APAP-induced liver injury in mice. Our results indicated that subchronic alcohol exposure significantly increased the mortality rate in APAP-overdosed mice. Alcohol pretreatment also exacerbated APAP-induced hepatic damage, as evidenced by elevated serum ALT and AST levels, enhanced inflammatory responses, and aggravated oxidative stress. Quantitative polymerase chain reaction (qPCR) analysis revealed that alcohol consumption suppressed mitochondrial biogenesis (MB)-related genes, including Pgc-1α and transcription factor A, mitochondrial (TFAM). Notably, macrophage depletion via clodronate liposomes not only attenuated hepatocyte injury and inflammation induction but also restored the expression of MB/function-related genes, including Pgc-1α, TFAM, and Opa1. These findings suggest macrophage-involved inflammatory amplification may aggravate APAP-induced liver injury, at least in part, by impairing mitochondrial adaptive repair responses.
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