Curcumin prevents and reverses cirrhosis induced by bile duct obstruction or CCl4 in rats: role of TGF-beta modulation and oxidative stress.
Curcumin is a phytophenolic compound, which is highly efficacious for treating several inflammatory diseases. The aim of this study was to evaluate the efficacy of curcumin in preventing or reversing liver cirrhosis. A 4-week bile duct ligation (BDL) rat model was used to test the ability of curcumin (100 mg/kg, p.o., daily) to prevent cirrhosis. To reverse cirrhosis, CCl(4) was administered chronically for 3 months, and then it was withdrawn and curcumin administered for 2 months. Alanine aminotransferase, gamma-glutamyl transpeptidase, liver histopathology, bilirubin, glycogen, reduced and oxidized glutathione, and TGF-beta (mRNA and protein) levels were assessed. Curcumin preserved normal values of markers of liver damage in BDL rats. Fibrosis, assessed by measuring hydroxyproline levels and histopathology, increased nearly fivefold after BDL and this effect was partially but significantly prevented by curcumin. BDL increased transforming growth factor-beta (TGF-beta) levels (mRNA and proteins), while curcumin partially suppressed this mediator of fibrosis. Curcumin also partially reversed the fibrosis induced by CCl(4). Curcumin was effective in preventing and reversing cirrhosis, probably by its ability of reducing TGF-beta expression. These data suggest that curcumin might be an effective antifibrotic and fibrolitic drug in the treatment of chronic hepatic diseases.
Reyes-Gordillo
Karina
K
Sección Externa de Farmacología, Cinvestav-IPN., Apdo. Postal 14-740, México 07000, D.F. México.
Segovia
José
J
Shibayama
Mineko
M
Tsutsumi
Victor
V
Vergara
Paula
P
Moreno
Mario G
MG
Muriel
Pablo
P
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D002251:Carbon Tetrachloride / Q000633:toxicity; D002252:Carbon Tetrachloride Poisoning / Q000517:prevention & control*; D002779:Cholestasis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D016212:Transforming Growth Factor beta; D002251:Carbon Tetrachloride; D003474:Curcumin