1-methylnicotinamide modulates IL-10 secretion and voriconazole metabolism

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 13, 2025

Background Inflammatory diseases impair the hepatic metabolism of voriconazole (VRC). 1-Methylnicotinamide (1-MNA), a common final metabolite nicotinamide in liver, has demonstrated anti-inflammatory effects recent studies. This study investigated impact 1-MNA on VRC liver. Method Mice with systemic inflammatory response induced by lipopolysaccharide (LPS) were intragastrically administered 1-MNA, and their metabolic capacity was evaluated. Kupffer cells primary hepatocytes isolated, flow cytometry along molecular knockdown experiments performed to explore mechanisms underlying improved drug metabolism. IL-10 knockout (IL-10 –/– ) mice used validate role enhancing hepatocyte under conditions. Results promoted M2 polarization liver cells, stimulated secretion, upregulated CYP2C38 expression hepatocytes, enhanced The mechanism which appears involve inhibition nuclear transcription factor NF-κB (p65) hepatocytes. Conclusions regulated cell an LPS-induced environment, reduced

Language: Английский

Targeting hepatic macrophages for non-alcoholic fatty liver disease therapy

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Sept. 5, 2024

Non-alcoholic fatty liver disease (NAFLD) and its more advanced form, non-alcoholic steatohepatitis (NASH), have become global health challenges with significant morbidity mortality rates. NAFLD encompasses several diseases, ranging from simple steatosis to severe inflammatory fibrotic forms. Ultimately, this can lead cirrhosis hepatocellular carcinoma. The intricate role of hepatic macrophages, particularly Kupffer cells (KCs) monocyte-derived macrophages (MoMFs), in the pathogenesis NASH, has received increasing attention. Hepatic interact hepatocytes, stellate cells, endothelial playing a crucial maintaining homeostasis. Paradoxically, they also participate some diseases. This review highlights fundamental emphasizing their plasticity contribution inflammation fibrosis, hopes provide ideas for subsequent experimental research clinical treatment.

Language: Английский

Inhibition of histone methyltransferase G9a aggravates phenotypic severity of hepatic lipotoxicity in non-alcoholic steatohepatitis (NASH)

Biochemical and Biophysical Research Communications, Journal Year: 2024, Volume and Issue: 743, P. 151171 - 151171

Published: Dec. 11, 2024

Language: Английский