Silymarin improves metabolism and disposition of aspirin in cirrhotic rats.
The profile of urinary salicylate metabolites was determined after an i.p. administration of acetylsalicylic acid (ASA) to CCl4-cirrhotic rats to rats which in addition to CCl4 received an oral dose of silymarin throughout the CCl4 treatment to produce cirrhosis and to control groups. ASA esterase activity was determined in serum and livers. The time course of plasma concentration of salicylates in similar groups was followed after the i.p. injection of ASA. The cirrhotic animals showed a lack of urinary glucuronides and an increase in urinary gentisic and salicylic acids. The activities of plasma and serum ASA esterase were significantly increased in cirrhosis and the plasma half-life of ASA was reduced. The simultaneous administration of silymarin (50 mg/kg of b.w.) along with CCl4, completely prevented all the alterations. The mechanism by which silymarin prevented those alterations is not completely known but our results establish the potential use of silymarin in cirrhotic patients to prevent disorders in drug metabolism and disposition frequently found in patients with liver diseases.
Mourelle
M
M
Departmento de Farmacologia y Toxicología, Centro de Investigación y de Estudios Avanzados del I.P.N., México, D.F.
Favari
L
L
D000818:Animals; D001241:Aspirin / Q000378:metabolism* / Q000493:pharmacokinetics; D002252:Carbon Tetrachloride Poisoning / Q000150:complications / Q000378:metabolism; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012459:Salicylates / Q000097:blood / Q000652:urine; D012838:Silymarin / Q000494:pharmacology*
D005419:Flavonoids; D012459:Salicylates; D012838:Silymarin; D002265:Carboxylic Ester Hydrolases; C018737:acetylsalicylic acid hydrolase; D001241:Aspirin