Effect of hyperglycaemia on the hepatic metabolism and excretion of xenobiotics.
The biliary excretion of drugs has been investigated in hyperglycaemic male Wistar rats. Hyperglycaemia was produced by a continuous infusion of glucose in different concentrations. To examine the effect of hyperglycaemia on the biliary excretion rate of xenobiotics, one representative of non-metabolizing exogenous organic anions (rose bengal) and metabolizing phenolic drugs (p-nitrophenol) as model compounds were used. A dose-dependent increase of blood and bile glucose level was found after the continuous infusion of glucose in a concentration of 10, 20 or 30%. Biliary flow and biliary excretion of rose bengal were significantly depressed in hyperglycaemic rats. Hepatic conjugation of p-nitrophenol with glucuronic acid appeared to be decreased, however, a compensatory increase of sulphoconjugation of p-nitrophenol was observed in hyperglycaemic rats. Biliary excretion of unconjugated p-nitrophenol was negatively influenced by high blood glucose level and the overall hepatic elimination of p-nitrophenol was also diminished by hyperglycaemia. Insulin (I U/kg i.v.) compensated partly the depressive effect of high blood sugar level on the biliary excretion rate of rose bengal, however, it was unable to abolish completely the negative effects of hyperglycaemia. These results indicate that hyperglycaemia does alter the hepatic elimination of xenobiotics.
Fischer
E
E
Department of Pharmacology, University Medical School, Pécs, Hungary.
Rafiel
A
A
Bojcsev
S
S
D000818:Animals; D001646:Bile / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006943:Hyperglycemia / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015262:Xenobiotics / Q000378:metabolism*
D001786:Blood Glucose; D015262:Xenobiotics; D005947:Glucose