Related Experiment Video
Updated: Apr 16, 2026
Partial Lobular Hepatectomy: A Surgical Model for Morphologic Liver Regeneration
Published on: May 31, 2018
A novel antioxidant multitarget iron chelator M30 protects hepatocytes against ethanol-induced injury
1National Key Disciplines for Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen 518112, China ; Department of Immunobiology, Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632, China ; Department of Anatomy, The University of Hong Kong, Pokfulam, Hong Kong.
Abstract:
The multitarget iron chelator, M30, is a novel antioxidant and protective agent against oxidative stress in a spectrum of diseases. However, there is no report regarding its role in liver diseases. Since oxidative stress is one of the major pathological events during the progression of alcoholic liver diseases, the protective effects and mechanisms of M30 on ethanol-induced hepatocyte injury were investigated in this study. Rat hepatocyte line BRL-3A was pretreated with M30 prior to ethanol treatment. Cell death, apoptosis, oxidative stress, and inflammation were examined. Specific antagonists and agonists were applied to determine the involvements of hypoxia inducible factor-1 alpha (HIF-1α) and its upstream adenylate cyclase (AC)/cyclic AMP (cAMP)/protein kinase A (PKA)/HIF-1α/NOD-like receptor 3 (NLRP3) inflammasome pathway. We found that M30 significantly attenuated ethanol-induced cellular death, apoptosis, production of reactive oxygen species (ROS), and secretion of inflammatory cytokines and inhibited activation of the AC/cAMP/PKA/HIF-1α/NLRP3 inflammasome pathway. Inhibition and activation of the AC/cAMP/PKA/HIF-1α pathway mimicked and abolished the effects of M30, respectively. In conclusion, inhibition of the AC/cAMP/PKA/HIF-1α/NLRP3 inflammasome pathway by M30 partially contributes to its attenuation of hepatocyte injury caused by ethanol exposure.
Insights
The iron chelator M30 protects liver cells from ethanol damage by reducing oxidative stress and inflammation. It works by inhibiting the AC/cAMP/PKA/HIF-1α/NLRP3 inflammasome pathway, offering a potential therapeutic strategy for alcoholic liver disease.
Area of Science:
- Hepatology
- Toxicology
- Molecular Biology
Background:
- Oxidative stress is a key factor in alcoholic liver disease progression.
- The multitarget iron chelator M30 demonstrates antioxidant and protective properties.
- M30's role in liver diseases, particularly alcoholic injury, remains unexplored.
Purpose of the Study:
- To investigate the protective effects of M30 against ethanol-induced hepatocyte injury.
- To elucidate the underlying mechanisms involving hypoxia-inducible factor-1 alpha (HIF-1α) and the NLRP3 inflammasome pathway.
Main Methods:
- Rat hepatocyte cell line (BRL-3A) was used.
- Cells were pretreated with M30 before ethanol exposure.
- Assays for cell death, apoptosis, oxidative stress, inflammation, and pathway activation were performed, utilizing specific antagonists and agonists.
Main Results:
- M30 significantly reduced ethanol-induced cell death, apoptosis, reactive oxygen species (ROS) production, and inflammatory cytokine secretion.
- M30 inhibited the activation of the adenylate cyclase (AC)/cyclic AMP (cAMP)/protein kinase A (PKA)/HIF-1α/NLRP3 inflammasome pathway.
- Modulating the AC/cAMP/PKA/HIF-1α pathway mimicked or abolished M30's protective effects.
Conclusions:
- M30 exhibits protective effects against ethanol-induced hepatocyte injury.
- Inhibition of the AC/cAMP/PKA/HIF-1α/NLRP3 inflammasome pathway is a key mechanism for M30's hepatoprotection.
- M30 represents a potential therapeutic agent for alcoholic liver disease.
