Depressed Hepatic Uptake and Low Biliary Excretion of Certain Foreign Organic Compounds during Oral Administration of Carbon Tetrachloride or Chloroform to Rats*

1973 ◽  
Vol 1 (6) ◽  
pp. 1322-1323
Author(s):  
MOHAMMED Z. BARAKAT ◽  
MAHMOUD M. ABOU-EL-MAKAREM
Keyword(s):  
Carbon Tetrachloride ◽  
Oral Administration ◽  
Organic Compounds ◽  
Biliary Excretion ◽  
Hepatic Uptake

MULTIPLE TRANSPORT SYSTEMS MEDIATE THE HEPATIC UPTAKE AND BILIARY EXCRETION OF THE METABOLICALLY STABLE OPIOID PEPTIDE [d-PENICILLAMINE2,5]ENKEPHALIN

2004 ◽  
Vol 33 (2) ◽  
pp. 287-293 ◽  
Author(s):  
Keith A. Hoffmaster ◽  
Maciej J. Zamek-Gliszczynski ◽  
Gary M. Pollack ◽  
Kim L. R. Brouwer
Keyword(s):  
Biliary Excretion ◽  
Opioid Peptide ◽  
Hepatic Uptake ◽  
Transport Systems

Efficient hepatic uptake and concentrative biliary excretion of a mercapturic acid

1998 ◽  
Vol 275 (4) ◽  
pp. G612-G619 ◽  
Author(s):  
Cheri A. Hinchman ◽  
James F. Rebbeor ◽  
Nazzareno Ballatori
Keyword(s):  
Rat Liver ◽  
Biliary Excretion ◽  
Organic Anion ◽  
Hepatic Uptake ◽  
Mercapturic Acid ◽  
Whole Body ◽  
Isolated Perfused Rat Liver ◽  
Mercapturic Acids ◽  
Anion Transporters ◽  
Subsequent Degradation

The role of the liver in the disposition of circulating mercapturic acids was examined in anesthetized rats and in the isolated perfused rat liver using S-2,4-dinitrophenyl- N-acetylcysteine (DNP-NAC) as the model compound. When DNP-NAC was infused into the jugular vein (150 or 600 nmol over 60 min) it was rapidly and nearly quantitatively excreted as DNP-NAC into bile (42–36% of the dose) and urine (48–62% of dose). Some minor metabolites were detected in bile (<4%), with the major metabolite coeluting on HPLC with the DNP conjugate of glutathione (DNP-SG). Isolated rat livers perfused single pass with 3 μM DNP-NAC removed 72 ± 9% of this mercapturic acid from perfusate. This rapid DNP-NAC uptake was unaffected by sodium omission, or byl-cysteine,l-glutamate,l-cystine, or N-acetylated amino acids, but was decreased by inhibitors of hepatic sinusoidal organic anion transporters (oatp), indicating that DNP-NAC is a substrate for these transporters. The DNP-NAC removed from perfusate was promptly excreted into bile, eliciting a dose-dependent choleresis. DNP-NAC itself constituted ∼75% of the total dose recovered in bile, reaching a concentration of 9 mM when livers were perfused in a recirculating mode with an initial DNP-NAC concentration of 250 μM. Other biliary metabolites included DNP-SG, DNP-cysteinylglycine, and DNP-cysteine. DNP-SG was likely formed by a spontaneous retro-Michael reaction between glutathione and DNP-NAC. Subsequent degradation of DNP-SG by biliary γ-glutamyltranspeptidase and dipeptidase activities accounts for the cysteinylglycine and cysteine conjugates, respectively. These findings indicate the presence of efficient hepatic mechanisms for sinusoidal uptake and biliary excretion of circulating mercapturic acids in rat liver and demonstrate that the liver plays a role in their whole body elimination.

Hepatic uptake and biliary excretion of tetracycline in the rat

1973 ◽  
Vol 225 (5) ◽  
pp. 1240-1246 ◽  
Author(s):  
RC Lanman ◽  
S Muranishi ◽  
LS Schanker
Keyword(s):  
Biliary Excretion ◽  
Hepatic Uptake

Pharmacology and toxicology of carbon tetrachloride in the sheep. IV. Reduction and augmentation of toxicity by selenium

1967 ◽  
Vol 18 (4) ◽  
pp. 667
Author(s):  
AC Kondos ◽  
GL McClymont
Keyword(s):  
Carbon Tetrachloride ◽  
Oral Administration ◽  
Fasciola Hepatica ◽  
Clinical Signs ◽  
Field Tests ◽  
High Protein Diet ◽  
Intramuscular Dose ◽  
History Of ◽  
Ccl4 Poisoning ◽  
Oral Doses

Susceptibility of sheep to toxic effects of carbon tetrachloride (CCl4) was assessed by determining the increase in plasma levels of isocitric dehydrogenase (ICD) and glutamic transaminase (GOT) and by other criteria. Susceptibility was increased by oral administration of 1 mg of selenium (Se) as sodium selenite plus 100 i.u. of tocopherol acetate on alternate days for 120 days, 2 mg Se per day for 21 days, and 6 mg Se per day for 6 days, before dosing with CCl4. Susceptibility was reduced by smaller total amounts of Se, and by oral doses of 6 mg Se per day for 3 days, a single oral or intramuscular dose of 5 or 12 mg c. 20 hr, or 5 or 12 mg orally 10–20 min, before dosing with CCl4. One 5 mg dose at 20 hr and a second 20 min before CCl4 was more effective than either alone. Sheep from two different sources differed considerably in their susceptibility to CCl4. In the more susceptible sheep Se administration reduced susceptibility to a level comparable with that shown by the naturally resistant animals. Administration of Se to sheep dosed with CCl4 and then given a high-protein diet resulted in lower GOT levels, milder clinical signs, and a great reduction in mortality. In field tests on properties with a recent history of CCl4 poisoning, oral administration of 5 mg Se about 20 min before CCl4 significantly reduced susceptibility. Administration of Se to fluke-infested sheep did not protect the liver fluke (Fasciola hepatica) against CCl4.

Release of catechol amines from the adrenal medulla by CCl4

1960 ◽  
Vol 198 (3) ◽  
pp. 682-685 ◽  
Author(s):  
Theodore M. Brody ◽  
Deane N. Calvert
Keyword(s):  
Carbon Tetrachloride ◽  
Adrenal Gland ◽  
Oral Administration ◽  
Adrenal Medulla ◽  
Catechol Amine ◽  
Single Oral Administration ◽  
Parallel Increase ◽  
Amine Content ◽  
Wet Weight ◽  
Catechol Amines

The single oral administration of an hepatotoxic dose of carbon tetrachloride (CCl4) causes a decrease in the amount of apparent epinephrine and norepinephrine in the adrenal medulla after 20 hours. There is also a parallel increase in the wet weight of the adrenal gland. The ability of CCl4 to induce catechol amine depletion has been demonstrated in both the rat and the rabbit. Adrenals of animals whose spinal cords have been transected prior to CCl4 administration do not exhibit this decrease in catechol amine content. These results will be discussed in the light of an hypothesis that the toxic action of CCl4 is an indirect one and may be mediated via a release of catechol amines.

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