Protective Effects of Antioxidant Raxofelast in Alcohol-Induced Liver Disease in Mice

Vol. 74, No. 1, 2005

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Original Paper

Protective Effects of Antioxidant Raxofelast in Alcohol-Induced Liver Disease in Mice
Domenica Altavilla^a, Herbert Marini^a, Paolo Seminara^a, Giovanni Squadrito^b, Letteria Minutoli^a, Maria Passaniti^a, Alessandra Bitto^a, Gioacchino Calapai^a, Margherita Calò^c, Achille P. Caputi^a, Francesco Squadrito^a

^aSection of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, and
^bDepartment of Internal Medicine, University of Messina, AOU 'G. Martino' Messina, and
^cDepartment of Veterinary Pharmacology, University of Messina, Messina, Italy

Address of Corresponding Author

Pharmacology 2005;74:6-14 (DOI: 10.1159/000082939)

Key Words

Alcohol
Lipid peroxidation
Toll-like receptor-4
Inflammatory cytokines

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- kappa B 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.

Author Contacts

Prof. Francesco Squadrito, MD
Department of Clinical and Experimental Medicine and Pharmacology
Section of Pharmacology, University of Messina AOU 'G. Martino' Torre Biologica
Via Consolare Valeria, Gazzi, IT-98125 Messina (Italy)
Tel. +39 0902213648, Fax +39 0902213300, E-Mail Francesco.Squadrito@unime.it

Article Information

Received: May 25, 2004
Accepted after revision: September 30, 2004
Published online: December 27, 2004
Number of Print Pages : 9
Number of Figures : 6, Number of Tables : 2, Number of References : 33

Medline Abstract (ID 15627848)

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