Decabromodiphenyl Ethane Sensitizes Zebrafish to Alcoholic Liver Injury by Compromising NAD+-Mediated Multicellular...

Area of Science:

• Environmental toxicology
• Hepatology
• Molecular toxicology

Background:

• Alcoholic liver disease (ALD) poses a significant global health burden.
• Environmental contaminants, such as brominated flame retardants, are increasingly recognized as potential contributors to liver injury.

Purpose of the Study:

• To investigate the impact of Decabromodiphenyl ethane (DBDPE) on the progression of alcoholic liver injury.
• To elucidate the underlying mechanisms of DBDPE-induced liver damage and impaired recovery.

Main Methods:

• Male zebrafish were pre-exposed to DBDPE followed by an acute ethanol challenge.
• Assessed liver tissue damage, lipid accumulation, mitochondrial function, and oxidative stress.
• Utilized single-cell transcriptomics to analyze pathway disruptions.
• Investigated the role of NAD+ deficiency and tested nicotinamide riboside supplementation.

Main Results:

• DBDPE exposure induced liver tissue damage, lipid accumulation, mitochondrial dysfunction, and oxidative stress in zebrafish.
• DBDPE pre-exposure significantly delayed recovery from ethanol-induced liver injury.
• Single-cell transcriptomics revealed DBDPE disrupted tight junction pathways and suppressed alcohol metabolism pathways, leading to cholestasis.
• NAD+ deficiency was identified as a key driver of DBDPE's adverse effects, and nicotinamide riboside supplementation mitigated these impairments.

Conclusions:

• DBDPE exacerbates alcoholic liver injury and impairs liver recovery in zebrafish by inducing mitochondrial dysfunction, oxidative stress, and cholestasis.
• NAD+ deficiency is a critical mechanism underlying DBDPE's hepatotoxicity.
• DBDPE represents a novel environmental risk factor contributing to the progression of alcoholic liver disease.