L. A. Griffiths

3′-O-Methyl-(+)-catechin glucuronide and 3′-O-methyl-(+)-catechin sulphate: new urinary metabolites of (+)-catechin in the rat and the marmoset

The major urinary metabolites of (+)-catechin (cyanidanol-3) in the rat were (+)-catechin glucuronide, 3′-O-methyl-(+)-catechin glucuronide and 3′-O-methyl-(+)-catechin sulphate. The latter conjugate was the major metabolite in marmoset urine.

The involvement of the gastro-intestinal mic̀roflora in nitro-compound-induced methaemoglobinaemia in rats and its relationship to nitrogroup reduction

Abstract The present study describes investigations into the methaemoglobinaemia-inducing capacity of three mono- and five dinitro-compounds in both normal and antibiotically pretreated rats in vivo, and in vitro on incubation with rat blood. The results obtained following administration of certain nitro-compounds indicated that the induction of methaemoglobinaemia and nitroreduction in vivo could occur independently of the gastro-intestinal microflora. The in vitro studies suggest that in some cases the conversion of haemoglobin to methaemoglobin could occur possibly as a result of a direct interaction between unchanged nitro-compounds and haemoglobin.

Metabolism of N-acylated and O-alkylated drugs by the intestinal microflora during anaerobic incubation in vitro.

1. The ability of the rat intestinal microflora to deacylate or dealkylate a large number of drugs and related compounds during anaerobic incubation in vitro has been explored.2. Evidence was obtained that the rat microflora is able to deacylate phenacetin and certain related compounds to the corresponding primary amines in vitro. Other N-acylated drugs investigated were found to be resistant to microbial deacylation.3. Of the O-alkylated compounds studied only certain of those possessing a simple benzenoid structure were susceptible to microfloral degradation. None of the N-alkylated drugs studied were dealkylated by the microflora.4. The influence of substitution on the susceptibility of drug molecules to microfloral degradation is discussed.

New metabolites of the naturally-occurring mutagen, quercetin, the pro-mutagen, rutin and of taxifolin.

The major biliary metabolites of the mutagen, quercetin, the pro-mutagen rutin and taxifolin have been identified by EI-mass spectrometry, UV-spectroscopy and chromatographic methods as conjugates of the corresponding 3′-O-methyl ethers. The toxicological significance of these findings is discussed.

3,5-Dihydroxyphenylpropionic acid, a further metabolite of sinapic acid

Aus Rattenurin wurde 3,5-Dihydroxyphenylpropionsäure als Metabolit der Sinapinsäure isoliert.

Enterohepatic cycling of O-(β-hydroxyethyl) rutosides and their biliary metabolites in the rat

O-(β-Hydroxyethyl)rutosides are shown to undergo reabsorption from the intestine following their secretion in bile.

Metabolism of a biliary metabolite of phenacetin and other acetanilides by the intestinal microflora.

In vivo, rat intestinal micro-organisms mediate the metabolic hydrolysis of the biliary metabolite(N-acetyl-p-aminophenyl glucuronide) of phenacetin and related compounds.

Metabolism of hydrazines and hydrazides by the intestinal microflora.

Intestinal microorganisms are able to effect the metabolic reductive fission of hydrazines but not hydrazides during incubation in vitro.

The prevention by (+)-cyanidanol-3 of hepatitis-induced changes in the disposition of imipramine in the rat

The administration of (+)-Cyanidanol-3 [+)-catechin) to the rat using a subchronic dosing regime based on that currently used in the therapy of acute viral hepatitis in man, largely prevented the changes in the disposition of a single dose of [14C]imipramine hydrochloride induced by the hepatotoxin, D-(+)-galactosamine hydrochloride in rats. Complete return to normal pharmacokinetics was not attained due to interaction between (+)-Cyanidanol-3 and imipramine. Biliary excretion of imipramine metabolites was 79.3% of the dose in control rats. This was reduced to 69.3 and 39.8% by the separate administration of (+)-catechin and galactosamine respectively. Concurrent administration of (+)-Cyanidanol-3 and galactosamine resulted in 64.8% of the imipramine dose appearing in bile. These results were reflected in changes in faecal and renal excretion of imipramine metabolites in surgically unmodified rats in which galactosamine injection caused an elevation of urinary excretion from 31.0 to 69.8% of the imipramine dose. Concurrent Cyanidanol administration reduced the effect of galactosamine so that only 46.9% was excreted in urine. These changes were due to decreased biliary excretion and increased renal excretion of the glucuronide conjugates of 2-hydroxyimipramine, 2-hydroxydesmethylimipramine and 10-hydroxyimipramine. None of the treatments used impaired the overall ability of the rat to metabolize imipramine, although the plasma clearance of imipramine was reduced by 42% as a result of galactosamine administration and by 21% during treatment with (+)-catechin alone or combined catechin and galactosamine treatment.

Metabolism of Xanthone in the Rat

Abstract1. The metabolism of xanthone by the rat has been investigated.2. The major unconjugated urinary metabolite was 4-hydroxyxanthone (24%). Smaller amounts of free 2-hydroxyxanthone (13%) and 3-hydroxy-xanthone (6%) were also formed. Other fluorescent metabolites were detected in trace amounts.3. Conjugates of 4-hydroxyxanthone and 2-hydroxyxanthone were detected in both urine and bile.4. No evidence was obtained for the formation of ring fission products.