Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Phase II Reactions: Acetylation Reactions01:24

Phase II Reactions: Acetylation Reactions

238
Acetylation, a phase II biotransformation reaction, introduces an acetyl group to drugs or their metabolites. Acetyltransferase enzymes facilitate this reaction, which resembles α-amino acid conjugation due to the addition of a functional group to the drug molecule.
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
238
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

4.9K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
4.9K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Differentiating Hepatic and Renal Toxicity Reveals CYP-Independent Mechanisms of Acetaminophen-Induced Acute Kidney Injury.

bioRxiv : the preprint server for biology·2026
Same author

Correction: Retrospective Observational Study To Analyse Indications of Cochleostomy and Changing Trends in Use of Cochleostomy for Cochlear Implant Electrode Insertion.

Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India·2026
Same author

Post-SARS CoV-2 infection laryngeal mucormycosis: a rare ail mimicking malignancy.

BMJ case reports·2026
Same author

Dysregulation of xenobiotic metabolism and mitochondrial dysfunction exacerbate acetaminophen-induced hepatotoxicity in human antigen R-deficient male mice.

Toxicology·2026
Same author

The Utility of Ultrasound Guidance for Quadricepsplasty in Complex Lower Extremity Deformities in Infants.

Indian journal of orthopaedics·2026
Same author

Understanding Liver and Digestive Diseases: A Paved Road to Improve Diagnosis, Management, and Treatment.

Exploration of digestive diseases·2026

Related Experiment Video

Updated: Jul 11, 2025

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
08:59

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

Published on: December 3, 2020

7.9K

High-Dose Acetaminophen with Concurrent CYP2E1 Inhibition Has Profound Anticancer Activity without Liver Toxicity.

Allyn Bryan1, Pavani Pingali1, Anthony Faber1

  • 1Department of Veterans Affairs, Richmond, Virginia. (A.B., P.P., W.S.L., B.P., A.N.); Departments of Oral and Craniofacial Molecular Biology (A.F.) and Human and Molecular Genetics (J.L., L.M.), Virginia Commonwealth University, Richmond, Virginia; Department of Veterans Affairs, Charleston, South Carolina (H.L.); and Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas, Lawrence, Kansas (J.Y.A., H.J.).

The Journal of Pharmacology and Experimental Therapeutics
|November 2, 2023
PubMed
Summary
This summary is machine-generated.

High-dose acetaminophen (AAP) can be safely administered for anticancer effects by co-administering CYP2E1 inhibitors like fomepizole. This strategy prevents liver toxicity, enabling dose escalation for potent anti-tumor activity.

More Related Videos

Partial Lobular Hepatectomy: A Surgical Model for Morphologic Liver Regeneration
05:37

Partial Lobular Hepatectomy: A Surgical Model for Morphologic Liver Regeneration

Published on: May 31, 2018

12.2K
Y-90 Radioembolization and PD-1 Inhibitor as Neoadjuvant Treatment in Hepatocellular Carcinoma
09:11

Y-90 Radioembolization and PD-1 Inhibitor as Neoadjuvant Treatment in Hepatocellular Carcinoma

Published on: May 24, 2024

450

Related Experiment Videos

Last Updated: Jul 11, 2025

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
08:59

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

Published on: December 3, 2020

7.9K
Partial Lobular Hepatectomy: A Surgical Model for Morphologic Liver Regeneration
05:37

Partial Lobular Hepatectomy: A Surgical Model for Morphologic Liver Regeneration

Published on: May 31, 2018

12.2K
Y-90 Radioembolization and PD-1 Inhibitor as Neoadjuvant Treatment in Hepatocellular Carcinoma
09:11

Y-90 Radioembolization and PD-1 Inhibitor as Neoadjuvant Treatment in Hepatocellular Carcinoma

Published on: May 24, 2024

450

Area of Science:

  • Pharmacology
  • Hepatology
  • Oncology

Background:

  • Acetaminophen (AAP) metabolism involves sulfation, glucuronidation, and CYP2E1-mediated conversion to toxic NAPQI.
  • CYP2E1 inhibition is a strategy for managing AAP toxicity, with N-acetylcysteine (NAC) and fomepizole being clinically relevant.
  • The therapeutic potential of high-dose AAP for anticancer activity is limited by dose-dependent hepatotoxicity.

Purpose of the Study:

  • To investigate the safety and efficacy of high-dose AAP with CYP2E1 inhibition for potential anticancer applications.
  • To assess the protective effects of fomepizole and NAC against AAP-induced liver toxicity.
  • To evaluate the in vitro and in vivo antitumor activity of AAP in combination with toxicity-mitigating agents.

Main Methods:

  • Mice were treated with acetaminophen (AAP) in combination with fomepizole (a CYP2E1 inhibitor) and N-acetylcysteine (NAC).
  • Liver toxicity was assessed using histology and serum chemistry.
  • Anticancer activity was evaluated in vitro and in vivo using 4T1 breast and Lewis lung carcinoma tumor models, including in immune-compromised mice.

Main Results:

  • Fomepizole, with or without NAC, completely prevented AAP-induced liver toxicity.
  • High-dose AAP (650 mg/kg) with NAC/fomepizole rescue demonstrated significant antitumor activity in vivo.
  • Antitumor efficacy was diminished in immune-compromised mice, suggesting an immune-mediated mechanism.

Conclusions:

  • Concurrent administration of CYP2E1 inhibitors allows for safe dose escalation of AAP to levels required for potent anticancer activity.
  • This approach mitigates AAP-induced hepatotoxicity, opening avenues for novel cancer therapeutic strategies.
  • The antitumor effects of high-dose AAP are at least partially dependent on an intact immune system.