Acute liver failure (ALF) is associated with a high mortality rate. The incidence of ALF is approximately 2000 cases annually. Drug-related hepatotoxicity accounts for more than 50% of cases in US. Effective treatment strategies aimed at accelerating liver regeneration could offer major benefits in patients with ALF.
We investigated the effect C1 esterase inhibitor (human) [C1-INH] on liver regeneration capabilities, using a murine model of carbon tetrachloride [CCl(4)]-induced ALF.
Male WT (C57BL6) mice were subjected CCl(4)-induced (2-4 mg/kg ip) ALF. The animals were pretreated with intravenous C1-INH (100, and 400 U/kg) or normal saline. Liver injury was evaluated using serum levels of alanine aminotransferase (ALT), serum interleukin-6 (IL-6), IL-1, TNF-alpha and specific markers of regeneration (BrdU staining) and hematoxylin and eosin staining.
There was dose dependant improvement in histology, serum IL-6, IL-1, TNF-alpha and ALT release associated with C1-INH treated ALF mice compared with ALF mice not treated with complement inhibition. Improved animal survival and increased number of BrdU positive cells were observed in C1-INH groups.
These data indicate that complement activation plays a key role in CCl(4)-induced acute liver failure. C1-INH, a multi-faceted inhibitor of complement system activation, represents a potential therapeutic strategy to promote liver regeneration ALF.
Saidi, R.: Grant/Research Support, VIROPHARMA.
To cite this abstract in AMA style:Saidi R, Rajeshkumar B, Walter O, Shariftabrizi A, Dresser K, Movahedi B, Jabbour N, Bozorgzadeh A. Effect of C1-Esterase Inhibitor (Human) on a Murine Acute Liver Failure Model, The [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/effect-of-c1-esterase-inhibitor-human-on-a-murine-acute-liver-failure-model-the/. Accessed May 6, 2021.
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