Fibrosis and glycogen stores depletion induced by prolonged biliary obstruction in the rat are ameliorated by metadoxine.
OBJECTIVE
To evaluate liver-beneficial properties of metadoxine, not related with alcohol metabolism, bioactivation of external toxins or antioxidant mechanisms, the chronic bile duct ligation (BDL) model was used and results were compared with colchicine.


METHODS
Seven groups (n=6) of male Wistar rats were used. Four groups were BDL and received metadoxine (60 mg/kg/12 h i.p.), colchicine (10 microg/rat/day/p.o.), both or vehicles; three groups were sham-appropriate controls. Collagen content was determined by measuring hydroxyproline in liver samples; malondialdehyde (MDA) was used to estimate lipid peroxidation levels; glycogen was determined utilizing the anthrone reagent; gomory's trichromic stains of liver sections were performed.


RESULTS
Collagen increased four-fold by BDL, metadoxine, colchicine or both prevented fibrosis partially; MDA levels increased three-fold by BDL and no treatment had any significant effect; glycogen was almost depleted in the cirrhotic group, metadoxine preserved glycogen; bilirubins, and alanine aminotransferase and gamma-glutamyltranspeptidase activities increased several-fold in the BDL group, and both drugs prevented these effects partially. The histopathological analysis correlated with biochemical data.


CONCLUSIONS
Both compounds showed similar antifibrotic properties; metadoxine was more effective in preserving glycogen. Besides its antioxidant effects and its ability to induce alcohol metabolism, metadoxine possesses important antifibrotic and antinecrotic properties, and maintains energy stores efficiently.
Muriel
Pablo
P
Sección Externa de Farmacología, Cinvestav-IPN Apdo, DF México. pamuriel@mail.cinvestav.mx
Deheza
Rogelio
R
D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000427:Alcohol Deterrents / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001663:Bilirubin / Q000097:blood; D001651:Cholestasis, Extrahepatic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003078:Colchicine / Q000008:administration & dosage / Q000627:therapeutic use; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004338:Drug Combinations; D006909:Hydroxyproline / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D011736:Pyridoxine / Q000008:administration & dosage / Q000627:therapeutic use*; D011761:Pyrrolidonecarboxylic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D005723:gamma-Glutamyltransferase / Q000097:blood
D000427:Alcohol Deterrents; D004338:Drug Combinations; D008112:Liver Glycogen; D003094:Collagen; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; C037845:metadoxine; D011736:Pyridoxine; D001663:Bilirubin; D006909:Hydroxyproline; D003078:Colchicine; D011761:Pyrrolidonecarboxylic Acid