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Biomedical subjects

J Magdalou

Publications and source records attributed to J Magdalou.

133 records · Page 8Linked to original sources
PubMed1979

The effect of dietary sulfur-containing amino acids on the activity of drug-metabolizing enzymes in rat-liver microsomes.

Male Wistar rats were fed either a balanced diet whose protein source was a mixture of amino acids (diet 1), or a similar diet which differed only in having 48% less the quantity of the sulfur-containing amino acids methionine and cystine (diet 2). The diets were given either continuously for 1 month or for 15 days after a protein-free diet. Both diets 1 and 2 permitted good growth of rats and relatively stable microsomal protein content. Protein depletion decreased the total proteins, total phospholipids, and cytochrome P-450 content, and it strongly increased UDP-glucuronosyltransferase activity in rat-liver microsomes. Repletion with diet 1 restored those values, to the level found in control rats. However, diet 2, given continuously induced an increase in UDP-glucuronosyltransferase activity and in the cytochrome P-450 concentration. Since high UDP-glucuronosyltransferase activity was related to lessened amounts of sulfur-containing amino acids in the diet, we discuss the possible effect of methionine and cystine on the regulation of glucuronoconjugation in relation to sulfoconjugation.

Amino Acids↗
PubMed1976

[Effect of gamma rays from 60Co on the in vitro incorporation of palmitic acid in lipids of rat liver microsomes].

The gamma-rays of 60Co cause a diminution in the incorporation of palmitic acid in the phosphatidic acids and the neutral fats of rat-liver microsomes. This diminution occurs without morphological change in the microsomal membranes, where the enzymes responsible for this incorporation are situated. Some evidence is offered that lipid peroxides may be involved in this inhibition.

Animals↗
PubMedDate not supplied

Glucuronidation of 2-arylpropionic acids pirprofen, flurbiprofen, and ibuprofen by liver microsomes.

Acylglucuronide formation from the 2-arylpropionic acids pirprofen, flurbiprofen, and ibuprofen, three nonsteroidal anti-inflammatory drugs (NSAIDs), was investigated in rat liver microsomes using an HPLC method and 14C-labeled UDP-glucuronic acid as co-substrate. Pirprofen was the best substrate of UDP-glucuronosyltransferase with a Vmax/Km of 45.4, as compared with 8.0 and 1.6 for flurbiprofen and ibuprofen, respectively. Glucuronidation of the drugs was significantly increased upon treatment of rats with phenobarbital; 3-methylcholanthrene or clofibrate failed to induce the activity. At the dose of 100 mg/kg body weight for 1, 3, and 5 days, pirprofen was unable to induce its own glucuronidation. However, this treatment caused a transient increase, after 1 day, of several isoform activities monitored with 4-nitrophenol, 1-naphthol, 4-methylumbelliferone, terpenes, and testosterone as substrates. After 3 and 5 days these activities were decreased, especially when glucuronidation of 4-nitrophenol and 4-methylumbelliferone was considered, glucuronidation of the terpenes cis-myrtanol, borneol, nopol, and of testosterone being similar to control values. By contrast to clofibrate, administration of pirprofen to rats decreased bilirubin UDP-glucuronosyltransferase in a time-dependent fashion with a maximal decrease of 59% after 5 days. Treatment of rats with pirprofen also decreased markedly the formation of flurbiprofen glucuronide. Comparison of NSAID glucuronidation between several species indicated that it was most potent in monkeys, dogs, and humans. Cats were also efficient in that respect. Gunn rats, which are genetically deficient in bilirubin glucuronidation, were able to form acylglucuronides from the drugs, thus indicating that these 2-arylpropionic acids were not substrates of the bilirubin isozyme.

Aged↗
PubMedDate not supplied

In vitro irreversible binding of ketoprofen glucuronide to plasma proteins.

Many aryl alkanoic acids are cleared as ester glucuronide excreted in urine. While conjugation with glucuronic acid is generally considered as a detoxication process, this conjugate has been shown over the past decade to be a potentially reactive metabolite, undergoing hydrolysis, intramolecular rearrangement, and irreversible binding to proteins. This study describes the in vitro degradation of biosynthetic ketoprofen glucuronide after incubation with human plasma, human serum albumin solutions at various concentrations (290 and 580 microM), and in protein-free buffer, in physiological conditions (pH = 7.4, 37 degrees C). The protein concentrations chosen correspond to that found in synovial fluid and plasma, respectively. Albumin catalyzed the hydrolysis of the glucuronide, but the extent of the reaction was not dependent on the protein concentration. The irreversible binding of ketoprofen was investigated in identical conditions. Maximal ketoprofen-adduct concentrations were achieved after 3 and 10 hr incubation, and were 6.65, 3.2, and 2.6% of initial ketoprofen in plasma and albumin solutions at 580 and 290 microM, respectively. The difference in binding between plasma and albumin (580 microM) could not be totally attributed to the other major plasma proteins, because no irreversible binding was detected with fibrinogen and gamma globulins, and only 0.14% of ketoprofen was bound to alpha and beta globulins after 3 hr incubation. The covalent interaction with albumin was proportional to conjugate concentration over the range studied (from 5 to 30 micrograms/ml or 11.62 to 69.72 microM).

Blood Proteins↗