DOI: 10.1073/pnas.081082098. An important function of Nrf2 in combating oxidative stress: Detoxification of acetaminophen

An important function of Nrf2 in combating oxidative stress: Detoxification of acetaminophen

10.1073/pnas.081082098

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Nrf2, a member of the “cap ‘n collar” group of transcription factors, is important for protecting cells against oxidative damage. We investigated its role in the detoxification of acetaminophen [ N -acetyl- p -aminophenol (APAP)]-induced hepatotoxicity. When Nrf2 knockout (Nrf2 −/− ) and wild-type mice were given APAP by i.p. injection, the Nrf2 −/− mice were highly susceptible to APAP treatment. With doses of APAP that were tolerated by wild-type mice, the Nrf2 −/− mice died of liver failure. When hepatic glutathione was depleted after a dose of 400 mg/kg of APAP, the wild-type mice were able to compensate and regain the normal glutathione level. In contrast, the glutathione level in the Nrf2 −/− mice was not compensated and remained low. This was because of the decrease in the gene expression of gcs H and gcs L as well as gss in the livers of the Nrf2 −/− mice. In addition, the expression of ugt 1a6 and gst pi that detoxify APAP by conjugation was also decreased. This increased susceptibility of the Nrf2 −/− mice to APAP, because of an impaired capacity to replenish their glutathione stores, compounded with a decreased detoxification capability, highlights the importance of Nrf2 in the regulation of glutathione synthesis and cellular detoxification processes.

Bibliography

Chan, K., Han, X.-D., & Kan, Y. W. (2001). An important function of Nrf2 in combating oxidative stress: Detoxification of acetaminophen. Proceedings of the National Academy of Sciences, 98(8), 4611â4616.

Authors 3

Kaimin Chan (first)
Xiao-Dong Han (additional)
Yuet Wai Kan (additional)

References 26 Referenced 641

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:44 a.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 5:29 p.m.)
Indexed	1 month ago (July 30, 2025, 10:14 a.m.)
Issued	24 years, 4 months ago (April 3, 2001)
Published	24 years, 4 months ago (April 3, 2001)
Published Online	24 years, 4 months ago (April 3, 2001)
Published Print	24 years, 4 months ago (April 10, 2001)

Funders 0

None

BibTeX

@article{Chan_2001, title={An important function of Nrf2 in combating oxidative stress: Detoxification of acetaminophen}, volume={98}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.081082098}, DOI={10.1073/pnas.081082098}, number={8}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Chan, Kaimin and Han, Xiao-Dong and Kan, Yuet Wai}, year={2001}, month=apr, pages={4611–4616} }

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