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Titolo:
MOLYBDATE DEPLETES HEPATIC 3-PHOSPHOADENOSINE 5-PHOSPHOSULFATE AND IMPAIRS THE SULFATION OF ACETAMINOPHEN IN RATS
Autore:
OGURO T; GREGUS Z; MADHU C; LIU L; KLAASSEN CD;
Indirizzi:
UNIV KANSAS,MED CTR,DEPT PHARMACOL TOXICOL & THERAPEUT,CTR ENVIRONM HLTH & OCCUPAT MED KANSAS CITY KS 66160 UNIV KANSAS,MED CTR,DEPT PHARMACOL TOXICOL & THERAPEUT,CTR ENVIRONM HLTH & OCCUPAT MED KANSAS CITY KS 66160
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 3, volume: 270, anno: 1994,
pagine: 1145 - 1151
SICI:
0022-3565(1994)270:3<1145:MDH35A>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
ADENOSINE 3'-PHOSPHATE 5'-PHOSPHOSULFATE; INORGANIC SULFATE; 3'-PHOSPHOADENOSINE 5'-PHOSPHOSULFATE; BILIARY-EXCRETION; INVIVO; LIVER; CHROMATOGRAPHY; HEPATOTOXICITY; DISPOSITION; METABOLISM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
40
Recensione:
Indirizzi per estratti:
Citazione:
T. Oguro et al., "MOLYBDATE DEPLETES HEPATIC 3-PHOSPHOADENOSINE 5-PHOSPHOSULFATE AND IMPAIRS THE SULFATION OF ACETAMINOPHEN IN RATS", The Journal of pharmacology and experimental therapeutics, 270(3), 1994, pp. 1145-1151

Abstract

Molybdate (15 mmol/kg p.o.) decreased serum sulfate concentrations ofrats 70% within 6 hr after administration. Parallel to this depletion, there was a dramatic decrease in hepatic sulfate and 3-phosphoadenosine 5-phosphosulfate (PAPS) concentrations (about 40 and 65%, respectively). However, renal PAPS concentrations did not change significantly. Molybdate reduced serum, hepatic and renal sulfate as well as hepatic PAPS concentration in a dose-dependent manner up to the dose of 10 mmol/kg. However, renal PAPS did not change. The results indicate that molybdate reduced not only sulfate concentrations in serum and tissue,but also PAPS concentrations in liver. The effect of molybdate on thepharmacokinetics of acetaminophen (AA, 150 mg/kg i.v.) was also investigated in order to determine whether molybdate-induced depletion of PAPS might be a useful tool for examining the importance of sulfation in the detoxication and toxication of xenobiotics. AA-sulfate concentration in blood decreased 40 and 80% after administration of molybdate at doses of 2.5 and 15 mmol/kg, respectively. Molybdate also decreased the excretion of AA-sulfate into bile and urine by about 60 and 80%, respectively. However, molybdate did not alter the excretion of AA-glucuronide and AA-glutathione/cysteine. The excretion of the parent AA increased 2-fold after molybdate administration (15 mmol/kg). In conclusion, molybdate effectively lowers inorganic sulfate in serum and tissues, and PAPS in the liver. Reduction of hepatic PAPS markedly decreases the sulfation of AA, suggesting that molybdate treatment could be used to study the importance of sulfation in pharmacology and toxicology.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/07/20 alle ore 14:50:29