Biomedical subjects

I Gasinska

Publications and source records attributed to I Gasinska.

3 recordsLinked to original sources

PubMed1993

Stereoselectivity in glutathione conjugation and amidase-catalyzed hydrolysis of the 2-bromoisovalerylurea enantiomers in the single-pass perfused rat liver.

Stereoselective glutathione conjugation and amidase-catalyzed hydrolysis of [(R)- and (S)-]2-bromoisovalerylurea (BIU), yielding bromoisovaleric acid (BI) and urea, have been observed in the rat in vivo and in isolated rat hepatocytes. The metabolism of enantiomeric (R)- and (S)-BIU was presently examined in the single-pass perfused rat liver with varying input concentrations (8-250 microM). Steady-state hepatic extraction ratios for (R)-BIU (0.6) were constant and higher than those for (S)-BIU, whose extraction ratio decreased from 0.36 (8 microM) to 0.23 (236 microM). (R)- and (S)-BIU were excreted unchanged only minimally into bile. [14C-Urea](R)-BIU underwent amidase-catalyzed hydrolysis to yield [14C]urea (15-24% of rate in) and conjugation to form the (S)-glutathionyl conjugate (31-35% of rate in); two metabolites, most likely the cysteinyl and dipeptide conjugates of BIU (10% of rate in), were found. [3H-Isovaleryl](S)-BIU formed much less amidase-hydrolyzed product, [3H]BI (1-2% of rate in) less (R)-glutathionyl conjugate (9-18% of rate in), but appreciable amounts (14-17% of rate in) of three other metabolites, of which two were most likely the cysteinyl and glycinylcysteinyl conjugates of BIU. When the glutathione conjugation products (glutathione, cysteine and cysteinylglycine conjugates) were summed, the total glutathione conjugation rate for (R)-BIU (44% of rate in) exceeded that for (S)-BIU (34 to 24% of rate in). Fitting of data to the Michaelis-Menten equation revealed similar Km for glutathione conjugation, but a 2-fold higher Vmax for (R)-BIU.(ABSTRACT TRUNCATED AT 250 WORDS)

Amidohydrolases↗

PubMed1988

Improved receptor assay for measuring digoxin activity.

We describe a receptor assay of digoxin activity involving Na+/K+-ATPase (EC 3.6.1.37) derived from human heart tissue. The procedure requires 500 microL of serum or plasma and incorporates one purification step, with Sep-Pak C18 cartridges (Waters). The method appears to be considerably more specific for digoxin and its cardio-active metabolites than are conventional immunoassays. Cardio-inactive metabolites and several digoxin-like factors cross react only slightly. The between-day coefficient of variation for the procedure ranged from 8.10% to 1.37% for digoxin concentrations between 0.5 and 5.0 nmol/L.

Animals↗

PubMedDate not supplied

Estimations of intestinal and liver first-pass metabolism in vivo. Studies on gentisamide conjugation in the rat.

In this paper a method is introduced to study both intestinal and liver metabolism in the intact rat by cannulation of the jugular vein, carotid artery, pyloric vein (into the portal vein), and bladder. In this preparation, the rat received an initial dose followed by iv (I) and then intraportal (II) infusions. Gentisamide (2,5-dihydroxybenzamide, GAM) was used since it forms monosulfate (GAM-2S and GAM-5S) and monoglucuronide (GAM-5G) conjugates, metabolites that are not further metabolized. After administration of tracer amounts of radiolabeled gentisamide ([3H]GAM), the concentration ratio of [3H]GAM in the portal vein and carotid artery [CPV(I)/CA(I)] during iv infusion, and the ratio of carotid artery concentrations for intraportal to iv infusions [CA(II)/CA(I)] provided the intestine and liver availabilities, respectively; the corresponding extraction ratios for the intestine and liver were 0.26 to 0.27 and 0.37 to 0.41. Similar concentration ratios for the conjugates during iv administration [CPV(I)/CA(I)] showed intestine formation of GAM-5G, and to a lesser extent, GAM-2S, since the ratios exceeded unity; GAM-5S was not formed by the intestine since the ratio was unchanged. The ratio of the carotid arterial concentrations for intraportal to iv infusions that revealed hepatic formation showed similar values (1.77 and 1.71) for GAM-2S and GAM-5S, but variable (decreases and increases) GAM-5G values, whose mean value approximated unity. All findings were consistent with data obtained from the perfused rat liver preparation and the combined perfusion of rat intestine-liver preparation, where GAM-5G and GAM-2S were shown to be formed by the intestine, and where sulfation was the preferred pathway in the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗