Resolution of liver fibrosis in chronic CCl4 administration in the rat after discontinuation of treatment: effect of silymarin, silibinin, colchicine and trimethylcolchicinic acid.
The purpose of this work was to obtain a suitable model of fibrosis, in which spontaneous reversion was minimal, to study the ability of silymarin, silibinin, colchicine and trimethylcolchicinic acid (TMCA) to reverse it. Reversal of liver fibrosis was studied in male Wistar rats after one, two or three months of CCl(4) administration (0.4 g/kg intraperitoneally, three times per week), by discontinuation of the toxin for 2 months. Silymarin (50 mg/kg), silibinin (50 mg/kg), colchicine (10 microg/rat) and trimethylcolchicinic acid (100 microg/rat) were administered daily, by gavage, after 3 months of CCl(4) administration. Collagen content was determined by measuring hydroxyproline in liver samples; glycogen, was determined utilizing the anthrone reagent; Mallory's trichromic stains of liver sections were performed. The best scheme of treatment was obtained when CCl(4) was administered during three months (collagen increased 6 times). Discontinuation of the toxin for two months produced a significant but relative small reduction of fibrosis (collagen was still 4.5 times over control). Colchicine, TMCA, silymarin or silibinin treatment showed no significant fibrolitic effect. This scheme of treatment may be an excellent tool to study the ability of drugs to reverse fibrosis. The hepatoprotective properties of silymarin, silibinin, colchicine and trimethylcolchinic acid may be irrelevant to reverse established cirrhosis.
Muriel
Pablo
P
External Section of Pharmacology, Cinvestav-I.P.N., P.O. Box 14-740, México 07000, D.F., México. pamuriel@mail-cinvestav.mx
Moreno
Mario G
MG
Hernández
María Del C
Mdel C
Chávez
Enrique
E
Alcantar
Lidia K
LK
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D003078:Colchicine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D003094:Collagen / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D020011:Protective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors
D008112:Liver Glycogen; D020011:Protective Agents; D012838:Silymarin; C009838:trimethylcolchicinic acid; D000077385:Silybin; D003094:Collagen; D002251:Carbon Tetrachloride; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D003078:Colchicine