Search PubMed⌕ Search

Biomedical subjects

Z Ben-Zvi

Publications and source records attributed to Z Ben-Zvi.

64 records · Page 4Linked to original sources
PubMedDate not supplied

Effects of clonidine and IBMX on sulfobromophthalein disposition in rats.

Clonidine, an alpha 2-adrenoceptor agonist, inhibited the biliary excretion, reduced the plasma clearance and increased the hepatic retention of sulfobromophthalein (BSP) in a dose related fashion in rats. The maximal effects of clonidine on BSP disposition occurred about 4 h after pretreatment. The effects of clonidine on biliary excretion and hepatic retention of BSP were retained following laparotomy (with or without bile duct cannulation); however, the effect of clonidine on plasma disappearance profile was not retained following abdominal surgery. Isobutylmethylxanthine (IBMX) affected BSP disposition in a similar fashion as clonidine, in rats without bile duct cannulation only; no effect of IBMX could be observed in bile duct cannulation rats. Yohimbine, an alpha 2-adrenoceptor antagonist, reversed the effects of clonidine, but not of IBMX, on BSP disposition. It thus seems that clonidine and IBMX exert their effects on BSP disposition by different mechanisms and probably at different sites.

1-Methyl-3-isobutylxanthine↗
PubMedDate not supplied

The effects of estrus cycle on drug metabolism in the rat.

The effect of the female rat estral cycle on microsomal drug metabolism in-vivo and in-vitro has been studied. Two microsomal enzymes, aminopyrine-N-demethylase and aniline hydroxylase showed a greater specific activity (p less than 0.01) in the diestrus phase of the estral cycle while the oxidative enzyme aryl hydrocarbon hydroxylase and the conjugative enzyme, glucuronyl transferase, were not affected. In vivo studies which included theophylline and antipyrine metabolism, and hexobarbital sleeping times showed no difference between the different phases of the estral cycle. Conflicting evidence about the effect of steroid sex hormones on hepatic drug metabolism is discussed.

Animals↗
PubMedDate not supplied

Urinary metabolites of caffeine in young dogs.

Urinary elimination of [1-methyl-14C]caffeine was investigated in young dogs. Mongrel dogs aged 2 days, 1 week, and 5 weeks received single doses of caffeine (50 mg/kg) through an orogastric tube. Eight dogs, each studied once, were involved. At identical times after the dose the ratio of urinary caffeine metabolites to unchanged caffeine was greatest in the 5-week-old and smallest in the 2-day-old puppy; cumulative ratios at (or very close to) the plateau of urinary excretion varied between 8.7 and 17.8 in the 5-week-old, 3.6 and 3.8 in the 1-week-old, and 2.2 and 2.4 in the 2-day-old dogs. The time needed to reach the plateau of the cumulative excretion of radioactivity in the urine decreased with age. Initially only caffeine was detected in the urine of the 2-day-old and 1-week-old dogs; the first quantitatively important metabolites were trimethyluric acid and 6-amino-5-(N-methylformylamino)-1,3 dimethyluracil (also known as 1,3,7-trimethyldihydrouric acid) in the 2-day-old, and the uracil derivative and theophylline in the 1-week-old and the 5-week-old puppies. The percentage of demethylated uric acid metabolites and uracil derivatives increased progressively with increasing age; this indicates increased demethylation, oxidation to uric acids and hydrolysis of the imidazole ring of caffeine with increasing age. These results are consistent with the previously reported slow plasma elimination of caffeine in the newborn and confirm the limited capacity of the young (as compared to the adult) mammal to metabolize caffeine.

Age Factors↗
PubMedDate not supplied

The metabolism and excretion of 14C-styrene oxide-glutathione adducts administered to the winter flounder, Pseudopleuronectes americanus, a marine teleost. Identification of the corresponding S-cysteine derivatives as major urinary metabolites.

The metabolism and excretion of intramuscularly administered 14C-glutathione conjugates of styrene oxide (Ia and IIa) were studied in the winter flounder at three dose levels. The various radiolabeled thioether metabolites excreted were separated by reverse-phase high pressure liquid chromatography, and identified and quantitated by cochromatography with synthetic standards. The urine was the major excretion route for radioactivity derived from the glutathione conjugates (up to 90%) at each dose level (1.0, 3.9, and 24.4 mg/fish) studied. The corresponding cysteine derivatives (Ic, IIc) were the major urinary metabolites although the N-acetylcysteine derivatives (Id, IId), or mercapturic acids, were also present in significant amounts at each dose and excretion interval examined. Unchanged glutathione conjugates of styrene oxide were the major radioactive constituents of 24-hr bile samples from the treated flounder, although significant amounts of the cysteinylglycine (Ib, IIb), cysteine, and N-acetylcysteine derivatives were also present in bile. Bile was a minor excretory route relative to urine. The oxidation of 14C-styrene to styrene 7,8-oxide by the cytochrome P-450-dependent monooxygenase system of hepatic microsomes of winter flounder was also demonstrated; likewise, styrene was converted to the diastereomeric glutathione conjugates of styrene 7,8-oxide by 9,000g supernatant fractions of flounder liver supplemented with glutathione. This study demonstrated that flounder liver can convert styrene to glutathione conjugates to styrene oxide and that mercapturic acid biosynthesis occurs after parenteral administration of a xenobiotic-glutathione adduct to this marine species, although the major urinary metabolites were the cysteine conjugates rather than the anticipated mercapturic acid derivatives.

Acetylcysteine↗