What question did this study set out to answer?

To investigate whether the transcription factor Nrf2 protects against acetaminophen-induced liver toxicity by regulating ARE-dependent detoxifying and antioxidant enzymes.

January 1, 2001Toxicological SciencesOpen Access

High Sensitivity of Nrf2 Knockout Mice to Acetaminophen Hepatotoxicity Associated with Decreased Expression of ARE-Regulated Drug Metabolizing Enzymes and Antioxidant Genes

View Full Paper

Ask AI

Bookmark

To investigate whether the transcription factor Nrf2 protects against acetaminophen-induced liver toxicity by regulating ARE-dependent detoxifying and antioxidant enzymes.
Male homozygous Nrf2 knockout and wild-type mice aged 2 to 4 months were treated orally with single doses of acetaminophen at 0, 150, 300, or 600 mg/kg.
Hepatic damage, mortality, alanine aminotransferase activity, hepatic non-protein sulfhydryls, and anti-acetaminophen immunoreactivity were evaluated across time points up to 24 hours.
Baseline expression levels and activities of detoxifying enzymes, including UDP-glucuronosyltransferase (Ugt1a6) and gamma-glutamylcysteine synthetase, were measured.
Acetaminophen doses of 300 mg/kg or higher caused mortality exclusively in Nrf2 knockout mice, alongside elevated plasma alanine aminotransferase levels and severe centrilobular hepatocellular necrosis.
Nrf2-deficient mice exhibited lower baseline hepatic non-protein sulfhydryl content and lower UDP-glucuronosyltransferase activity, corresponding to decreased mRNA expression of Ugt1a6 and gamma-glutamylcysteine synthetase heavy chain.

Discussion

No takes yet. Share an insight, caveat, or question.

Implication

In vivo animal study reveals increased acetaminophen-induced liver damage and mortality in Nrf2-deficient mice, indicating essential protective roles for ARE-regulated detoxifying enzymes.

Cite This Study

Ayako Enomoto (2001) studied this question.

synapsesocial.com/papers/6a0887d27de338f10b10c30d https://doi.org/10.1093/toxsci/59.1.169

View Full Paper

Ask AI

Bookmark

Implication

In vivo animal study reveals increased acetaminophen-induced liver damage and mortality in Nrf2-deficient mice, indicating essential protective roles for ARE-regulated detoxifying enzymes.

High Sensitivity of Nrf2 Knockout Mice to Acetaminophen Hepatotoxicity Associated with Decreased Expression of ARE-Regulated Drug Metabolizing Enzymes and Antioxidant Genes

Key Points

Discussion

Implication

Cite This Study

High Sensitivity of Nrf2 Knockout Mice to Acetaminophen Hepatotoxicity Associated with Decreased Expression of ARE-Regulated Drug Metabolizing Enzymes and Antioxidant Genes

Key Points

Discussion

Implication

Cite This Study

Also Consider

Also Consider