Effect of taurine on biliary excretion and metabolism of acetaminophen in male hamsters.
The effect of taurine intake on the biliary disposition and toxicity of acetaminophen (APAP) was examined in male Golden-Syrian hamsters. Animals were provided with taurine (5 mM) in drinking water for 1 week followed by APAP treatment (250 mg/kg, i.p.). Biliary excretion and plasma concentrations of APAP and its major metabolites were determined for up to 360 min. Taurine increased the bile flow, whereas the concentration of APAP or the metabolites in bile was not altered significantly. Accordingly the total biliary excretion of APAP and the metabolites was increased in hamsters fed taurine. Taurine increased the plasma concentrations of APAP-glutathione (GSH) and APAP-mercapturate, but the APAP-glucuronide or APAP-sulfate concentration was not changed. The area under the curve of the plasma APAP concentration was reduced significantly, suggesting that the elimination of APAP was enhanced by taurine intake. However, the hepatotoxicity resulting from a dose of APAP (450 mg/kg, i.p.) was not altered by taurine intake as determined by the elevation of serum alanine aminotransferase, aspartate aminotransferase, and sorbitol dehydrogenase activities. The results suggest that taurine administration could affect the disposition of APAP by enhancing its metabolism through the GSH-dependent pathway and also by increasing the biliary excretion of this drug and its metabolites. The pharmacological significance of this finding remains to be examined.
Lee
Ja Yong
JY
College of Pharmacy, Seoul National University, Seoul, Korea.
Jung
Da Woon
DW
Park
Hyun Ah
HA
Kim
Soo Jeong
SJ
Chung
Jin Ho
JH
Moon
Chang Kiu
CK
Kim
Young Chul
YC
D000082:Acetaminophen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D001646:Bile / Q000201:enzymology / Q000378:metabolism*; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System; D004305:Dose-Response Relationship, Drug; D008297:Male; D008647:Mesocricetus; D013654:Taurine / Q000494:pharmacology*; D013997:Time Factors
D018712:Analgesics, Non-Narcotic; D013654:Taurine; D000082:Acetaminophen; C037386:acetaminophen glucuronide; D003577:Cytochrome P-450 Enzyme System; C045667:acetaminophen sulfate ester; C034780:3-(glutathion-S-yl)acetaminophen