studies

1140A AASLD ABSTRACTS HEPATOLOGY, October, 2015
1910
The role of CD36 in acetaminophen-induced hepatotoxicity
in mice
chen zhang 1 , Xianmin Mu 1 , Che Xu 1 , Shi Hu 1 , Yuanfang Lu 1 ,
Qiang You 1,2 ; 1 Department of Biotherapy, Second Affiliated Hospital,
Nanjing Medical University, Nanjing, China; 2 Department of
Immunology, Nanjing Medical University, Nanjing, China
Acetaminophen (APAP) overdose cause hepatotoxicity, and
even acute liver failure, which involves a series of critical events
including APAP metabolite protein adduct formation, mitochondrial
dysfunction, oxidant stress, peroxynitrite formation and
nuclear DNA fragmentation. Recent studies indicate that sterile
inflammation and innate immune cells may play important roles
in APAP-induced liver injury and repair. CD36 is a member of
the class B scavenger receptor family of cell surface proteins. It
binds a variety of ligands including collagen, thrombospondin,
erythrocytes parasitized with Plasmodium falciparum, oxidized
low density lipoprotein, native lipoproteins, oxidized phospholipids,
and long-chain fatty acids. CD36 also assembles
with Toll-like receptor 4 and 6 to promote sterile inflammation.
The present study aims to investigate the role of CD36
in APAP induced murine liver injury. Methods: WT C57BL/6J
and CD36 -/- mice on same background were intraperitoneally
injected with APAP (300mg/kg) after fasting for 16h. The
blood and liver tissues were collected at 8h and 24h after
treatment. Liver injury was evaluated by serum ALT level and
liver tissue H&E staining. Liver inflammatory factors expression
was determined by real time PCR. The metabolite of APAP,
N-acetyl-p-benzoquinone imine (NAPQI) protein adducts, and
Cytochrome P450 2E1 (CYP2E1) level were measured by
Western blot. Liver infiltrating macrophages and neutrophils
were characterized by flow cytometry. Results: Compared with
WT mice, APAP treated CD36 -/- mice show less liver injury indicated
by serum ALT level and liver tissue H&E staining. There
was no significant difference in NAPQI-protein adducts and
CYP2E1 expression between these two strains. However, less
IL-1β and CXCL1 mRNA expression were observed in APAP
treated CD36 -/- mice as well as infiltrating macrophages and
neutrophils. Conclusion: APAP treated CD36 -/- mice have less
liver damage than WT mice which correlates with the extent of
inflammation. CD36 could be a new target to reduce APAP-induced
liver injury.
Disclosures:
The following authors have nothing to disclose: chen zhang, Xianmin Mu, Che
Xu, Shi Hu, Yuanfang Lu, Qiang You
1911
Withaferin-A Reduces Acetaminophen-Induced Liver
Injury in Mice
Ravirajsinh Jadeja 1 , Nathalie H. Urrunaga 2 , Suchismita Dash 2 ,
Neeraj K. Saxena 2 , Sandeep Khurana 1 ; 1 Gastroenterology and
Hepatology, Georgia Regents University, Augusta, MD; 2 Gastroenterology
and Hepatology, University of Maryland School of Medicine,
Baltimore, MD
Acetaminophen (APAP) overdose induces oxidative stress that
leads to hepatocyte necrosis. Withaferin-A (WA), a lactone,
has anti-oxidant activities however, its therapeutic potential
in APAP hepatotoxicity is unknown. The aim of our study was
to assess the therapeutic potential of WA in a mouse model
that mimics APAP-induced liver injury (AILI) in humans. Overnight
fasted C57BL/6NTac male mice (56 wk. old) received
200 mg/kg APAP intraperitoneally (i.p.). An hour later mice
were treated with 40 mg/kg WA or vehicle i.p., and euthanized
at 4 and 16 h; their livers were harvested and serum collected
for analysis. At 4 h, compared to vehicle-treated mice,
WA-treated mice had reduced serum ALT levels (P < 0.05),
hepatocyte necrosis (P