Acrolein Adduct Accumulation Causes Alcoholic Liver Disease


ALD is a major cause of morbidity and mortality worldwide and in the United States, with no FDA approved therapy. Also, it remains unclear why only some heavy alcohol drinkers develop clinically relevant ALD. Poor understanding of ALD pathogenesis impedes prevention, early diagnosis, and treatment of the disease. ER stress-UPR has recently been established as a significant mechanism contributing to ALD, however the mediators and mechanisms of alcohol-induced ER stress and liver injury are not fully understood. Alcohol consumption and metabolism increases oxidative stress and LPO of PUFAs, and generates aldehydes, among which acrolein is the most reactive and toxic. Acrolein can exert potent cellular toxicity by forming irreversible covalent adducts with proteins thereby interfering with their function. Acrolein is primarily metabolized and removed by the enzyme GSTP by conjugation to GSH.


Acrolein & Alcoholic Liver Disease Hypothesis leads to AlcoholGSTPdown regulationAcrolein proliferation, which promotes liver ER stress, apoptosis, steatosis & injury Acrolein andAcrolein AdductsER stressApoptosisSteatosisInjuryAlcoholic Liver DiseaseAcrolein clearance by scavengers like hydralazine inhibits alcoholic liver disease Hydralazine(AcroleinScavenger)

Acrolein formation and acrolein-adduct accumulation, occurring as a consequence of alcohol consumption and GSTP downregulation, is a significant event that critically mediates alcohol-induced ER stress/UPR, apoptosis and liver injury, thereby contributing to ALD pathogenesis. Acrolein clearance by scavengers will attenuate hepatic injury in ALD.

About Researcher

Principal Investigator

Swati Joshi-Barve

Swati Joshi-Barve, PhD

Assistant Professor of Medicine

E-mail Dr. Joshi-Barve


Biochemistry, University of Kentucky
University of Poona
University of Poona

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