Protective effects of antioxidant raxofelast in alcohol-induced liver disease in mice.

Abstract

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.

• Authors: Domenica Altavilla, Herbert Marini, Paolo Seminara, Giovanni Squadrito, Letteria Minutoli, Maria Passaniti, Alessandra Bitto, Gioacchino Calapai, Margherita Calò, Achille P Caputi, Francesco Squadrito
• Journal: Pharmacology (Pharmacology) Vol. 74 Issue 1 Pg. 6-14 (Apr 2005) ISSN: 0031-7012 [Print] Switzerland
• PMID: 15627848 (Publication Type: Journal Article)
• Copyright: Copyright (c) 2005 S. Karger AG, Basel

Chemical References

• Antioxidants
• Benzofurans
• Interleukin-6
• NF-kappa B
• Receptors, Immunologic
• Tlr4 protein, mouse
• Toll-Like Receptor 4
• Triglycerides
• Tumor Necrosis Factor-alpha
• Intercellular Adhesion Molecule-1
• Vitamin E
• Malondialdehyde
• Alanine Transaminase
• Glutathione
• Raxofelast

Topics

• Alanine Transaminase (metabolism)
• Animals
• Antioxidants (pharmacology)
• Benzofurans (pharmacology)
• Female
• Glutathione (metabolism)
• Intercellular Adhesion Molecule-1 (biosynthesis, genetics)
• Interleukin-6 (biosynthesis, genetics)
• Lipid Peroxidation (drug effects)
• Liver (drug effects, metabolism, pathology)
• Liver Diseases, Alcoholic (prevention & control)
• Liver Function Tests
• Malondialdehyde (metabolism)
• Mice
• Mice, Inbred C57BL
• NF-kappa B (metabolism)
• Receptors, Immunologic (biosynthesis, genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Toll-Like Receptor 4
• Triglycerides (metabolism)
• Tumor Necrosis Factor-alpha (biosynthesis, genetics)
• Vitamin E (analogs & derivatives, pharmacology)