PMID- 32841665
OWN - NLM
STAT- MEDLINE
DCOM- 20201106
LR  - 20201106
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 260
DP  - 2020 Nov 1
TI  - Febuxostat mitigates concanavalin A-induced acute liver injury via modulation of 
      MCP-1, IL-1beta, TNF-alpha, neutrophil infiltration, and apoptosis in mice.
PG  - 118307
LID - S0024-3205(20)31059-6 [pii]
LID - 10.1016/j.lfs.2020.118307 [doi]
AB  - AIM: Liver plays a crucial role in innate immunity reactions. This role 
      predisposes the liver to innate-mediated liver injury when uncontrolled 
      inflammation occurs. In this study, the effect of febuxostat administration on 
      acute liver injury induced by concanavalin A (Con A) injection into mouse eye 
      orbital sinus was studied. MATERIALS AND METHODS: Two doses of febuxostat (10 and 
      20 mg/kg, orally) were administered either 1 h before or 30 min after the 
      administration of Con A. Febuxostat at a low dose (10 mg/kg) before and after Con 
      A modulated the elevation of serum ALT, liver uric acid, liver myeloperoxidase 
      (MPO), and interleukin-1beta (IL-1beta) induced by Con A. The same dose of febuxostat 
      before Con A also decreased serum total bilirubin and neutrophil infiltration, as 
      evidenced by flow cytometry and histopathological analysis. KEY FINDINGS: 
      Febuxostat at a high dose (20 mg/kg) significantly improved serum ALT, AST, 
      albumin, total bilirubin, liver uric acid, MPO, monocyte chemoattractant 
      protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), interleukin-4 (IL-4), 
      IL-1beta, and neutrophil infiltration induced by Con A administration. The results 
      of histopathological examination of liver cells paralleled the observed 
      biochemical improvements. Hepatocyte apoptosis as evidenced by 
      immunohistochemical examination of cleaved caspase-3 was markedly decreased in 
      the febuxostat protection and treatment groups, in a dose-dependent manner 
      SIGNIFICANCE: These results indicate that febuxostat, especially at the higher 
      dose, may be an effective inhibitor of immune reactions evoked by Con A 
      administration.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Maresh, Mohammed M
AU  - Maresh MM
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura 
      University, 35516 Mansoura, Egypt.
FAU - Abdelaziz, Rania R
AU  - Abdelaziz RR
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura 
      University, 35516 Mansoura, Egypt.. Electronic address: rania200582@mans.edu.eg.
FAU - Ibrahim, Tarek M
AU  - Ibrahim TM
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura 
      University, 35516 Mansoura, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20200822
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 101V0R1N2E (Febuxostat)
RN  - 11028-71-0 (Concanavalin A)
RN  - 268B43MJ25 (Uric Acid)
RN  - EC 1.11.1.7 (Peroxidase)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Caspase 3/analysis
MH  - Chemokine CCL2/*analysis
MH  - Concanavalin A/*pharmacokinetics
MH  - Febuxostat/*administration & dosage/pharmacology
MH  - Hepatitis/immunology/physiopathology/*prevention & control
MH  - Interleukin-1beta/*analysis
MH  - Liver/chemistry/pathology/physiopathology
MH  - Male
MH  - Mice
MH  - Neutrophil Infiltration/drug effects
MH  - Neutrophils/drug effects/pathology
MH  - Peroxidase/analysis
MH  - Tumor Necrosis Factor-alpha/*analysis
MH  - Uric Acid/analysis
OTO - NOTNLM
OT  - Acute liver injury
OT  - Concanavalin A
OT  - Febuxostat
OT  - MCP-1
OT  - Neutrophils infiltration
EDAT- 2020/08/26 06:00
MHDA- 2020/11/11 06:00
CRDT- 2020/08/26 06:00
PHST- 2020/06/19 00:00 [received]
PHST- 2020/08/10 00:00 [revised]
PHST- 2020/08/18 00:00 [accepted]
PHST- 2020/08/26 06:00 [pubmed]
PHST- 2020/11/11 06:00 [medline]
PHST- 2020/08/26 06:00 [entrez]
AID - S0024-3205(20)31059-6 [pii]
AID - 10.1016/j.lfs.2020.118307 [doi]
PST - ppublish
SO  - Life Sci. 2020 Nov 1;260:118307. doi: 10.1016/j.lfs.2020.118307. Epub 2020 Aug 
      22.