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Am J Physiol Gastrointest Liver Physiol 284: G321-G327, 2003. First published August 28, 2002; doi:10.1152/ajpgi.00230.2002
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Vol. 284, Issue 2, G321-G327, February 2003

Curcumin prevents alcohol-induced liver disease in rats by inhibiting the expression of NF-kappa B-dependent genes

Amin A. Nanji1, Kalle Jokelainen2, George L. Tipoe3, Amir Rahemtulla4, Peter Thomas5, and Andrew J. Dannenberg6

1 Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104-4283; 2 Research Unit of Alcohol Diseases, Helsinki University Central Hospital, Helsinki, Finland; 3 Department of Anatomy, The University of Hong Kong, Hong Kong; 4 Department of Pathology, Harvard Medical School, Boston 02115; 5 Department of Surgery, Boston University School of Medicine, Boston, Massachusetts 02118; and 6 Department of Medicine, Weill Medical College of Cornell University and Anne Fisher Nutrition Center at Strang Cancer Prevention Center, New York, New York 10021

Induction of NF-kappa B-mediated gene expression has been implicated in the pathogenesis of alcoholic liver disease (ALD). Curcumin, a phenolic antioxidant, inhibits the activation of NF-kappa B. We determined whether treatment with curcumin would prevent experimental ALD and elucidated the underlying mechanism. Four groups of rats (6 rats/group) were treated by intragastric infusion for 4 wk. One group received fish oil plus ethanol (FE); a second group received fish oil plus dextrose (FD). The third and fourth groups received FE or FD supplemented with 75 mg · kg-1 · day-1 of curcumin. Liver samples were analyzed for histopathology, lipid peroxidation, NF-kappa B binding, TNF-alpha , IL-12, monocyte chemotactic protein-1, macrophage inflammatory protein-2, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and nitrotyrosine. Rats fed FE developed fatty liver, necrosis, and inflammation, which was accompanied by activation of NF-kappa B and the induction of cytokines, chemokines, COX-2, iNOS, and nitrotyrosine formation. Treatment with curcumin prevented both the pathological and biochemical changes induced by alcohol. Because endotoxin and the Kupffer cell are implicated in the pathogenesis of ALD, we investigated whether curcumin suppressed the stimulatory effects of endotoxin in isolated Kupffer cells. Curcumin blocked endotoxin-mediated activation of NF-kappa B and suppressed the expression of cytokines, chemokines, COX-2, and iNOS in Kupffer cells. Thus curcumin prevents experimental ALD, in part by suppressing induction of NF-kappa B-dependent genes.

antioxidants; cyclooxygenase; nitric oxide


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