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Biomedical subjects

S Rendic

Publications and source records attributed to S Rendic.

7 recordsLinked to original sources
PubMed1999

Metabolism of anabolic steroids by recombinant human cytochrome P450 enzymes. Gas chromatographic-mass spectrometric determination of metabolites.

Metabolism of steroid hormones with anabolic properties was studied in vitro using human recombinant CYP3A4, CYP2C9 and 2B6 enzymes. The enzyme formats used for CYP3A4 and CYP2C9 were insect cell microsomes expressing human CYP enzymes and purified recombinant human CYP enzymes in a reconstituted system. CYP3A4 enzyme formats incubated with anabolic steroids, testosterone, 17alpha-methyltestosterone, metandienone, boldenone and 4-chloro-1,2-dehydro-17alpha-methyltestosterone, produced 6beta-hydroxyl metabolites identified as trimethylsilyl (TMS)-ethers by a gas chromatography-mass spectrometry (GC-MS) method. When the same formats of CYP2C9 were incubated with the anabolic steroids, no 6beta-hydroxyl metabolites were formed. Human lymphoblast cell microsomes expressing human CYP2B6 incubated with the steroids investigated produced traces of 6beta-hydroxyl metabolites with testosterone and 17alpha-methyltestosterone only. We suggest that the electronic effects of the 3-keto-4-ene structural moiety contribute to the selectivity within the active site of CYP3A4 enzyme resulting in selective 6beta-hydroxylation.

Anabolic Agents↗
PubMed1994

Binding of (+)- and (-)-isomers and racemate of etomoxir to human serum albumin and effect of stearic acid and stanozolol.

Binding of (+)- and (-)-isomers and the racemate of sodium 2[6-(4-chlorophenoxy)-hexyl]-oxiran-2-carboxylate dihydrat (etomoxir) to the human serum albumin (HSA) was studied by the gel filtration method. The experimental results are presented graphically using the method of Scatchard. Measurements revealed the following data on the binding: (a) for either of the isomers there are two independent and nonequivalent classes of binding sites on the HSA molecule; (b) the binding constants calculated for both isomers were of the same order of magnitude (K1/n approximately 20 x 10(5) L.mol-1 for the concentration range 3.48-4.0 x 10(-5) mol.L-1, and K2/n approximately 2 x 10(5) L.mol-1 for the concentration range 4.28-10 x 10(-5) mol.L-1, for the high and low affinity binding sites, respectively); (c) statistically significant difference (p < or = 0.05) between the low affinity binding constant estimated for the (+)-isomer K2 = 1.9 +/- 0.1 x 10(5) L.mol-1) compared with the constants evaluated for the (-)-isomer and racemic etomoxir (2.6 +/- 0.1 and 2.9 +/- 0.2 x 10(5) L.mol-1, respectively); and (d) both isomers are bound into a high extent to the HSA molecule (i.e., at a ligand concentration of 3.48 x 10(-5) mol.L-1, the percent of binding was approximately 95% for the compound tested. When plotting the percent binding (% Cb) against the total concentration (Ctot), a statistically significant difference (p < or = 0.05) was obtained between the slope of the straight line for the (+)-isomer and those for other two compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding, Competitive↗
PubMed1982

Stereochemical characterization of interactions of chiral 1,4-benzodiazepine-2-ones with liver microsomes.

Microsomal P-450 cytochrome are stereoselective toward 7-Chloro-1,3-dihydro-3(S)-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one. (S)-1, and 7-chloro-1,3-dihydro-3(S)-isopropyl-5-phenyl-2H-1,4-benzodiazepin-2-one, (S)-2. (S)-enantiomers bind to a substrate binding site which accomodates the stable M-conformation (Ks =0.01 to 0.018 mmol/l). (R)-enantiomers, however, undergo a ligand type of interaction (Ks = 0.036 to 0.12 mmol/l). Prochiral desmethyldiazepam behaves similarly to the (S)-enantiomers of the above compounds. The ligand binding site does not differentiate between M- and P-conformers.

Animals↗
PubMed1982

[Prevention by metyrapone of halothane induced liver necrosis in rats (author's transl)].

Liver necrosis and an increase of serum sorbitol dehydrogenase activity can be produced in rats by halothane anesthesia (1% v/v in oxygen) following pretreatment with polychlorinated biphenyls. Using this model, it was shown that administration of metyrapone (2-methyl-1,2-bis(3-pyridyl)-1-propanone) (100 mg/kg b.w.) 1 h prior to anesthesia prevents liver necrosis and the concomitant increase in serum sorbitol dehydrogenase activity. No significant differences were observed when halothane was applied in air instead of oxygen, but the protective effect of metyrapone was abolished.

Animals↗