Curcumin prevents alcohol-induced liver disease in rats by inhibiting the expression of NF-kappa B-dependent genes.
Induction of NF-kappaB-mediated gene expression has been implicated in the pathogenesis of alcoholic liver disease (ALD). Curcumin, a phenolic antioxidant, inhibits the activation of NF-kappaB. 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-kappaB 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-kappaB 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-kappaB 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-kappaB-dependent genes.
Nanji
Amin A
AA
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104-4283, USA. amin.nanji@uphs.upenn.edu
Jokelainen
Kalle
K
Tipoe
George L
GL
Rahemtulla
Amir
A
Thomas
Peter
P
Dannenberg
Andrew J
AJ
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000097:blood / Q000633:toxicity; D003474:Curcumin / Q000494:pharmacology*; D000431:Ethanol / Q000097:blood / Q000633:toxicity; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000502:physiology; D007728:Kupffer Cells / Q000187:drug effects / Q000502:physiology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002492:Central Nervous System Depressants; D018836:Inflammation Mediators; D016328:NF-kappa B; D012333:RNA, Messenger; D017392:Thiobarbituric Acid Reactive Substances; D000431:Ethanol; D000410:Alanine Transaminase; D003474:Curcumin