Exploring Endogenous Tryptamines: Overlooked Agents Against Fibrosis in Chronic Disease? A Narrative Review DOI Creative Commons
Hunter Korsmo

Livers, Journal Year: 2024, Volume and Issue: 4(4), P. 615 - 637

Published: Nov. 28, 2024

Long regarded as illicit substances with no clinical value, N-dimethylated tryptamines—such N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, and bufotenine—have been found to produce naturally in a wide variety of species, including humans. Known for their psychoactive effects through serotonin receptors (5-HTRs), tryptamines are currently being reinvestigated clinically long-term benefits mental disorders. Endogenous tryptamine is methylated by indolethylamine-N-methyltransferase (INMT), which can then serve an agonist pro-survival pathways, such sigma non-opioid intracellular receptor 1 (SIGMAR1) signaling. Fibrogenic diseases, like metabolic-associated fatty liver disease (MAFLD), steatohepatitis (MASH), chronic kidney (CKD) have shown changes INMT SIGMAR1 activity the progression pathogenesis. At cellular level, endothelial cells fibroblasts express various tissues; however, little known about injury fibrosis. In this review, I will give overview biochemistry, molecular biology, current evidence INMT’s role hepatic fibrogenesis. also discuss pre-clinical findings N-methylated highlight new upcoming therapeutic strategies that may be adapted mitigating fibrogenic diseases. Finally, mention recent mutualistic gut bacteria influencing endogenous signaling metabolism.

Language: Английский

Hepatic microtubule destabilization facilitates liver fibrosis in the mouse model of Wilson disease DOI Creative Commons
Som Dev,

Yixuan Dong,

James P. Hamilton

et al.

Journal of Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Language: Английский

Citations

0
Probing Liver Injuries Induced by Thioacetamide in Human In Vitro Pooled Hepatocyte Experiments DOI Open Access
Himanshu Goel,

Richard L. Printz,

Venkat R. Pannala

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3265 - 3265

Published: March 13, 2024

Animal studies are typically utilized to understand the complex mechanisms associated with toxicant-induced hepatotoxicity. Among alternative approaches animal studies, in vitro pooled human hepatocytes have potential capture population variability. Here, we examined effect of hepatotoxicant thioacetamide on hepatocytes, divided into five lots, obtained from forty diverse donors. For 24 h, were exposed vehicle, 1.33 mM (low dose), and 12 (high dose) thioacetamide, followed by RNA-seq analysis. We assessed gene expression variability using heat maps, correlation plots, statistical variance. used KEGG pathways co-expression modules identify underlying physiological processes/pathways. The module analysis showed that majority lots exhibited activation for bile duct proliferation module. Despite lot-to-lot variability, identified a set common differentially expressed genes across similarities their response amino acid, lipid, carbohydrate metabolism. also efflux transporters found larger patterns, indicating alteration toxicant bioavailability within cells, which could turn affect patterns between lots. Overall, our highlights challenges toxicity.

Language: Английский

Citations

2
Exploring Endogenous Tryptamines: Overlooked Agents Against Fibrosis in Chronic Disease? A Narrative Review DOI Creative Commons
Hunter Korsmo

Livers, Journal Year: 2024, Volume and Issue: 4(4), P. 615 - 637

Published: Nov. 28, 2024

Long regarded as illicit substances with no clinical value, N-dimethylated tryptamines—such N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, and bufotenine—have been found to produce naturally in a wide variety of species, including humans. Known for their psychoactive effects through serotonin receptors (5-HTRs), tryptamines are currently being reinvestigated clinically long-term benefits mental disorders. Endogenous tryptamine is methylated by indolethylamine-N-methyltransferase (INMT), which can then serve an agonist pro-survival pathways, such sigma non-opioid intracellular receptor 1 (SIGMAR1) signaling. Fibrogenic diseases, like metabolic-associated fatty liver disease (MAFLD), steatohepatitis (MASH), chronic kidney (CKD) have shown changes INMT SIGMAR1 activity the progression pathogenesis. At cellular level, endothelial cells fibroblasts express various tissues; however, little known about injury fibrosis. In this review, I will give overview biochemistry, molecular biology, current evidence INMT’s role hepatic fibrogenesis. also discuss pre-clinical findings N-methylated highlight new upcoming therapeutic strategies that may be adapted mitigating fibrogenic diseases. Finally, mention recent mutualistic gut bacteria influencing endogenous signaling metabolism.

Language: Английский

Citations

0