The role of cytochrome P4502E1 in ethanol mediated diseases: a narrative update DOI
Samir Zakhari, Manuela G. Neuman, Helmut K. Seitz

et al.

Alcohol and Alcoholism, Journal Year: 2025, Volume and Issue: 60(3)

Published: March 25, 2025

Abstract Cytochrome P450 (CYPs) superfamily of enzymes metabolize thousands endogenous and exogenous substrates including ethanol. Results: P4502E1 (CYP2E1) is involved in ethanol metabolism as part the so-called microsomal metabolizing system, fatty acids some drugs such acetaminophen isoniazid, activation a variety procarcinogens (PCs). Chronic consumption induces CYP2E1 which may result an enhanced these to their toxic intermediates, generation carcinogens. In addition, oxidation increases associated with reactive oxygen species (ROS). This oxidative stress important driver for development alcohol-associated liver disease (AALD) alcohol-mediated cancer (AMC). ROS bind directly proteins DNA. also lead lipid peroxidation (LPO) LPO products. These products DNA forming etheno-DNA adducts. Cell culture studies well animal experiments have shown that knock-out animals or inhibition by chemicals results significant improvement histology. pathogenesis hepatic steatosis fibrosis. More recent patients AALD demonstrated serum transaminase activities when was inhibited clomethiazole. addition its role ROS, enhances PCs decreases level retinol retinoic acid liver. Conclusion: Inhibition improve inhibit AMC.

Language: Английский

The role of cytochrome P4502E1 in ethanol mediated diseases: a narrative update DOI
Samir Zakhari, Manuela G. Neuman, Helmut K. Seitz

et al.

Alcohol and Alcoholism, Journal Year: 2025, Volume and Issue: 60(3)

Published: March 25, 2025

Abstract Cytochrome P450 (CYPs) superfamily of enzymes metabolize thousands endogenous and exogenous substrates including ethanol. Results: P4502E1 (CYP2E1) is involved in ethanol metabolism as part the so-called microsomal metabolizing system, fatty acids some drugs such acetaminophen isoniazid, activation a variety procarcinogens (PCs). Chronic consumption induces CYP2E1 which may result an enhanced these to their toxic intermediates, generation carcinogens. In addition, oxidation increases associated with reactive oxygen species (ROS). This oxidative stress important driver for development alcohol-associated liver disease (AALD) alcohol-mediated cancer (AMC). ROS bind directly proteins DNA. also lead lipid peroxidation (LPO) LPO products. These products DNA forming etheno-DNA adducts. Cell culture studies well animal experiments have shown that knock-out animals or inhibition by chemicals results significant improvement histology. pathogenesis hepatic steatosis fibrosis. More recent patients AALD demonstrated serum transaminase activities when was inhibited clomethiazole. addition its role ROS, enhances PCs decreases level retinol retinoic acid liver. Conclusion: Inhibition improve inhibit AMC.

Language: Английский

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