ATC Abstracts

American Transplant Congress abstracts

  • Home
  • Meetings Archive
    • 2020 American Transplant Congress
    • 2019 American Transplant Congress
    • 2018 American Transplant Congress
    • 2017 American Transplant Congress
    • 2016 American Transplant Congress
    • 2015 American Transplant Congress
    • 2013 American Transplant Congress
  • Keyword Index
  • Resources
    • 2016 Resources
      • 2016 Welcome Letter
      • ATC 2016 Program Planning Committees
      • ASTS Council 2015-2016
      • AST Board of Directors 2015-2016
    • 2015 Resources
      • 2015 Welcome Letter
      • ATC 2015 Program Planning Committees
      • ASTS Council 2014-2015
      • AST Board of Directors 2014-2015
      • 2015 Conference Schedule
  • Advanced Search

In a Murine Model of Acetaminophen-Mediated Liver Injury, Tubastatin-a, An Hdac6-Specific Inhibitor, Improves Survival and Decreases Hepatocellular Injury

C. S. OBrien1, P. T. Hernandez1, S. J. Concors1, L. N. Krumeich1, Z. Wang1, G. Ge1, T. Bhatti2, A. Kozikowski3, W. Hancock2, M. H. Levine1

1Department of Surgery, University of Pennsylvania, Philadelphia, PA, 2Department of Pathology, Children's Hospital of Pennsylvania, Philadelphia, PA, 3Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL

Meeting: 2020 American Transplant Congress

Abstract number: 408

Keywords: Hepatocytes, Liver failure, Liver transplantation, Tissue-specific

Session Information

Date: Saturday, May 30, 2020

Session Name: Basic: Ischemia Reperfusion & Organ Rehabilitation II

Session Time: 3:15pm-4:45pm

 Presentation Time: 4:03pm-4:15pm

Location: Virtual

Related Abstracts
  • Tubastatin-A, an HDAC6 Inhibitor, is Protective in Liver Ischemia Reperfusion Injury and Acetaminophen-Mediated Liver Injury
  • Histone Deacetylase-6 Inhibition Mitigates Liver Ischemia-Reperfusion Injury and Acetaminophen Toxicity in Mice

*Purpose: Tylenol (APAP) toxicity, due to its narrow therapeutic window, is the leading cause of acute liver failure in the United States, resulting in approximately 30,000 hospital admissions and 500 deaths annually in spite of the use of N-acetyl-cysteine (NAC) therapy. Histone deacetylases (HDACs) are enzymes that alter gene expression, regulating diverse cellular processes. We have previously shown that Tubastatin-A (TubA), an HDAC6 inhibitor, provides protection from hepatic ischemia reperfusion injury. We now report that TubA is also protective and increases survival in a murine model of acetaminophen toxicity.

*Methods: Fasted, male wild type C57BL/6 (B6) mice were treated with vehicle, TubA, or NAC, at 16 hours and one hour prior to administration of APAP (500 mg/kg). Serum ALT and AST were measured in each group 24 hours after APAP administration. Each group was monitored for 14 days by an investigator blinded to treatment condition; time of death was recorded. Liver glutathione was measured in fasted B6 mice, and in mice treated with either vehicle, NAC, or TubA 6 hours after APAP induced liver injury.

*Results: TubA-treated mice developed significantly less hepatocellular injury compared to controls or mice treated with NAC after APAP administration (Fig 1a/b). TubA-treated mice had improved survival compared to controls or NAC-treated mice (Fig 1c). Liver glutathione levels are significantly reduced after APAP administration in controls and NAC-treated mice but are preserved in TubA-treated mice (Figure 2).

*Conclusions: TubA provides greater protection than NAC in an APAP model of liver injury. TubA mediated protection against APAP induced liver injury is associated with increased hepatic glutathione stores. These new findings, taken together with previously shown effects in hepatic ischemia reperfusion injury, suggest that TubA is a potent inhibitor of hepatocellular injury.

 border=

  • Tweet
  • Email
  • Print

To cite this abstract in AMA style:

OBrien CS, Hernandez PT, Concors SJ, Krumeich LN, Wang Z, Ge G, Bhatti T, Kozikowski A, Hancock W, Levine MH. In a Murine Model of Acetaminophen-Mediated Liver Injury, Tubastatin-a, An Hdac6-Specific Inhibitor, Improves Survival and Decreases Hepatocellular Injury [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/in-a-murine-model-of-acetaminophen-mediated-liver-injury-tubastatin-a-an-hdac6-specific-inhibitor-improves-survival-and-decreases-hepatocellular-injury/. Accessed March 8, 2021.

« Back to 2020 American Transplant Congress

Most Viewed Abstracts

  • This Week
  • This Month
  • All Time
  • Subtherapeutic Low Tacrolimus Trough Levels (≤3.5 Ng /ml) Are A Risk Factor For Acute Rejection And Creatinine Doubling.
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • Penis Transplantation: First U.S. Experience.
  • Is There a Difference Between DCD and DBD Kidney Transplantation with Similar KDPI?
  • Live Related Kidney Transplant Experience in Abuja, Nigeria – First Eight Cases Ever.
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • Subtherapeutic Low Tacrolimus Trough Levels (≤3.5 Ng /ml) Are A Risk Factor For Acute Rejection And Creatinine Doubling.
  • Penis Transplantation: First U.S. Experience.
  • Is There a Difference Between DCD and DBD Kidney Transplantation with Similar KDPI?
  • A Decade of Donor-Derived Disease: A Report of the OPTN Ad Hoc Disease Transmission Advisory Committee (DTAC).
  • Penis Transplantation: First U.S. Experience.
  • Is There a Difference Between DCD and DBD Kidney Transplantation with Similar KDPI?
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • Evidence of a Clinically Significant Drug-Drug Interaction between Cannabidiol and Tacrolimus: A Case Report
  • Kidney Dialysis after Heart Transplantation: The Short and Long Term Outcomes

Visit Our Partner Sites

American Transplant Congress (ATC)

Visit the official site for the American Transplant Congress »

American Journal of Transplantation

The official publication for the American Society of Transplantation (AST) and the American Society of Transplant Surgeons (ASTS) »

American Society of Transplantation (AST)

An organization of more than 3000 professionals dedicated to advancing the field of transplantation. »

American Society of Transplant Surgeons (ASTS)

The society represents approximately 1,800 professionals dedicated to excellence in transplantation surgery. »

Copyright © 2013-2021 by American Society of Transplantation and the American Society of Transplant Surgeons. All rights reserved.

Privacy Policy

loading Cancel
Post was not sent - check your email addresses!
Email check failed, please try again
Sorry, your blog cannot share posts by email.
This site uses cookies: Find out more.