PMID- 15627848
OWN - NLM
STAT- MEDLINE
DCOM- 20050901
LR  - 20131121
IS  - 0031-7012 (Print)
IS  - 0031-7012 (Linking)
VI  - 74
IP  - 1
DP  - 2005 Apr
TI  - Protective effects of antioxidant raxofelast in alcohol-induced liver disease in 
      mice.
PG  - 6-14
AB  - We investigated the effect of raxofelast on lipid peroxidation inhibition in mice 
      exposed to chronic ethanol. Female C57BL/6 mice were fed a modified 
      Lieber-DeCarli liquid ethanol (ETOH) or control diet (sham ETOH) for up to 14 
      days. Animals were assigned to receive either raxofelast (20 mg/kg/day i.p.) or 
      its vehicle (DMSO:NaCl 0.9% 1:1, v:v; 1 ml/kg i.p.). Serum alanine 
      aminotransferase (ALT), plasma and liver triglyceride levels, hepatic 
      malondialdehyde (MDA), reduced glutathione (GSH) concentrations, liver gene 
      expression of Toll-like receptor-4 (TLR-4), interleukin-6 (IL-6), tumor necrosis 
      factor-alpha (TNF-alpha) and intercellular adhesion molecule-1 (ICAM-1) were 
      studied at the end of the study. A histological evaluation of liver damage was 
      also carried out. Raxofelast, an analog of vitamin E, blunted the increased 
      hepatic nuclear factor-kappaB activity, reduced serum ALT, plasma and liver 
      triglycerides, lowered hepatic MDA levels, prevented liver GSH depletion and 
      decreased TLR-4, TNF-alpha, IL-6 and ICAM-1 hepatic gene expression. Furthermore 
      raxofelast ameliorated liver damage. Our results suggest that raxofelast blunts 
      the inflammatory cascade and organ damage during chronic ethanol exposure.
CI  - Copyright (c) 2005 S. Karger AG, Basel
FAU - Altavilla, Domenica
AU  - Altavilla D
AD  - Section of Pharmacology, Department of Clinical and Experimental Medicine and 
      Pharmacology, University of Messina, AOU G. Martino Messina, Italy.
FAU - Marini, Herbert
AU  - Marini H
FAU - Seminara, Paolo
AU  - Seminara P
FAU - Squadrito, Giovanni
AU  - Squadrito G
FAU - Minutoli, Letteria
AU  - Minutoli L
FAU - Passaniti, Maria
AU  - Passaniti M
FAU - Bitto, Alessandra
AU  - Bitto A
FAU - Calapai, Gioacchino
AU  - Calapai G
FAU - Calo, Margherita
AU  - Calo M
FAU - Caputi, Achille P
AU  - Caputi AP
FAU - Squadrito, Francesco
AU  - Squadrito F
LA  - eng
PT  - Journal Article
DEP - 20041227
PL  - Switzerland
TA  - Pharmacology
JT  - Pharmacology
JID - 0152016
RN  - 0 (Antioxidants)
RN  - 0 (Benzofurans)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Triglycerides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 1406-18-4 (Vitamin E)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - EC 2.6.1.2 (Alanine Transaminase)
RN  - GAN16C9B8O (Glutathione)
RN  - TC0T0O9VYO (Raxofelast)
SB  - IM
MH  - Alanine Transaminase/metabolism
MH  - Animals
MH  - Antioxidants/*pharmacology
MH  - Benzofurans/*pharmacology
MH  - Female
MH  - Glutathione/metabolism
MH  - Intercellular Adhesion Molecule-1/biosynthesis/genetics
MH  - Interleukin-6/biosynthesis/genetics
MH  - Lipid Peroxidation/drug effects
MH  - Liver/drug effects/metabolism/pathology
MH  - Liver Diseases, Alcoholic/*prevention & control
MH  - Liver Function Tests
MH  - Malondialdehyde/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/metabolism
MH  - Receptors, Immunologic/biosynthesis/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Toll-Like Receptor 4
MH  - Triglycerides/metabolism
MH  - Tumor Necrosis Factor-alpha/biosynthesis/genetics
MH  - Vitamin E/*analogs & derivatives/pharmacology
EDAT- 2005/01/04 09:00
MHDA- 2005/09/02 09:00
CRDT- 2005/01/04 09:00
PHST- 2004/05/25 00:00 [received]
PHST- 2004/09/30 00:00 [accepted]
PHST- 2005/01/04 09:00 [pubmed]
PHST- 2005/09/02 09:00 [medline]
PHST- 2005/01/04 09:00 [entrez]
AID - 82939 [pii]
AID - 10.1159/000082939 [doi]
PST - ppublish
SO  - Pharmacology. 2005 Apr;74(1):6-14. doi: 10.1159/000082939. Epub 2004 Dec 27.