# Human CYP2B6 in alcohol metabolism and alcoholic liver injury

> **NIH NIH R21** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $183,469

## Abstract

Project Summary:
Excessive consumption of alcohol is a major contributor to the global burden of morbidity and mortality, and is
the cause of alcoholic liver disease (ALD) that accounts for up to 25% of alcohol-associated deaths worldwide.
The spectrum of ALD ranges from relatively mild hepatic steatosis, alcoholic steatohepatitis and fibrosis, to
irreversible cirrhosis and hepatocellular carcinoma. Epidemiological studies reveal that binge drinking, a high-
risk alcohol consumption style, has become increasingly popular among young adults; and frequent binge
drinkers are at higher risk for developing severe ALD. However, the mechanisms underlying alcohol binge-
induced liver injury and whether there is an adaptive enzymatic system that metabolizes high concentrations of
ethanol after binge drinking are poorly understood. Our preliminary data demonstrate that chronic ethanol
feeding plus binge administration drastically induces hepatic expression of the cytochrome P450 2b10
(Cyp2b10) in mice. After alcohol binge ingestion blood ethanol levels of Cyp2b10-null mice were significantly
higher than that of wild-type mice. Moreover, chronic-plus-binge ethanol feeding resulted in greater liver
damage in Cyp2b10-null mice than that in wild-type mice. These exciting findings have led to the overarching
hypothesis that human CYP2B6, the analog of murine Cyp2b10, plays an important role in binge drinking-
induced ALD, and that adaptive induction of CYP2B6 enzyme coordinates a novel protective mechanism
underlying ALD. We will test this hypothesis in two proposed specific aims: Aim 1 is to determine CYP2B6-
mediated metabolism of ethanol in human liver cells; and Aim 2 will investigate the role of CYP2B6 in ethanol
binge-induced liver injury in humanized mouse model. These studies will provide necessary groundwork for
identifying and validating a novel metabolic pathway-mediated by CYP2B6/Cyp2b10 for adaptive metabolism
and detoxification of excessive alcohol after binge ingestion.

## Key facts

- **NIH application ID:** 10256633
- **Project number:** 5R21AA028521-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Hongbing Wang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $183,469
- **Award type:** 5
- **Project period:** 2020-09-10 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10256633

## Citation

> US National Institutes of Health, RePORTER application 10256633, Human CYP2B6 in alcohol metabolism and alcoholic liver injury (5R21AA028521-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10256633. Licensed CC0.

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