Metabolism and excretion of the liver-protective agent (+)-catechin in experimental hepatitis

Abstract

1. Following oral administration of [U-¹⁴C](+)-catechin to rats with galactosaminehepatitis, the biliary and faecal elimination of (+)-catechin metabolites was decreased compared with that in normal animals, Renal excretion of (+)-catechin metabolites was enhanced in galactosamine-hepatitis.

2. Although the biliary metabolites were present in similar proportions in galactosamine-hepatitis animals and controls, the major urinary metabolite, 3′-O-methyl (+)-catechin sulphate, was markedly decreased whereas 3′-O-methyl (+)-catechin glucuronide was increased by over 100%.

3. The total overall excretion of 3′-O-methyl (+)-catechin conjugates in rats with galactosamine-hepatitis was similar to that in normal animals indicating that catechol-O-methyltransferase activity is not significantly depressed in galactosamine-hepatitis.

4. Clearance of radioactivity from the blood following i.v. administration of [U-¹⁴C]-(+)-catechin was prolonged in galactosamine-hepatitis.

5. Liver perfusion experiments demonstrated depressed glucuronylation of (+)-catechin metabolites in galactosamine-hepatitis, whereas in liver homogenates synthesis of glucuronide conjugates of (+)-catechin metabolites was enhanced.

6. Lung slices were able to metabolize (+)-catechin and the lung is proposed as an extrahepatic site of (+)-catechin metabolism of increased importance in galactosamine-hepatitis.

7. The effects of galactosamine-hepatitis upon the structure of the hepatocyte plasma membrane are discussed in relation to decreased biliary excretion and glucuronylation.