Session Name: Ischemia Reperfusion & Organ Rehabilitation
Session Date & Time: None. Available on demand.
*Purpose: Liver Ischemia reperfusion injury (IRI) and Acetaminophen (APAP) toxicity are important causes of acute liver failure in the United States, that lack effective 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 IRI and APAP toxicity. We now report that the protective effect of TubA is preserved in a lymphocyte deficient model.
*Methods: Female Rag-1 -/- mice were treated with vehicle or TubA, at 16 hours and one hour prior to either 60 minutes of warm IRI or administration of APAP (500 mg/kg). Serum ALT and AST were measured in each group 24 hours after IRI or APAP administration.
*Results: Liver IRI in Rag-1 -/- mice resulted in a significant injury (AST 13,196 +/-2410, ALT 6851 +/-2953), with TubA treatment resulting in significantly lower AST (AST 4272 +/-3411, p=0.02, ALT 2991 +/-2309, p=0.06) (Figure 1). APAP toxicity in Rag-1 -/- mice resulted in significant injury as well (AST 16,251 +/- 6142, ALT 9363 +/- 2899). TubA treatment resulted in significantly lower AST/ALT (AST 778 +/-600, p=0.008 ALT 889 +/- 834, p=0.008) (Figure2).
*Conclusions: TubA provides protection from both liver IRI and APAP toxicity. This protection is maintained in lymphocyte deficient mice, suggesting that TubAs mechanism of action is not via the lymphocytes. Further understanding of the mechanism of TubA will assist in the treatment of liver injury.
To cite this abstract in AMA style:O'Brien CS, Hernandez P, Wang Z, Ge G, Kozikowski A, Hancock W, Levine MH. Tubastatin-a Mediated Protection from Liver Injury is Preserved in a Lymphocyte Deficient Model [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/tubastatin-a-mediated-protection-from-liver-injury-is-preserved-in-a-lymphocyte-deficient-model/. Accessed June 22, 2021.
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