scholarly journals The metabolism of phenylmercury by the rat

1972 ◽  
Vol 129 (4) ◽  
pp. 961-967 ◽  
Author(s):  
J. W. Daniel ◽  
J. C. Gage ◽  
P. A. Lefevre
Keyword(s):  
Small Proportion ◽  
Microsomal Fraction ◽  
Inorganic Mercury ◽  
Elemental Mercury ◽  
Microsomal Enzymes ◽  
Single Subcutaneous Dose ◽  
Subcutaneous Dose ◽  
Liver Homogenates

The metabolism of [U-14C]phenylmercury acetate was studied in the rat. After a single subcutaneous dose a small proportion is excreted unchanged in urine, and a larger amount in bile with some resorption from the gut. The greater part of the dose is broken down in the tissues to yield inorganic mercury which is excreted mainly in faeces, and conjugates of phenol and quinol are excreted in urine. In experiments in vitro phenylmercury is broken down by liver homogenates to release inorganic mercury and benzene; this reaction is effected by the soluble, but not the microsomal, fraction and does not require NADPH or NADH. No elemental mercury is formed under these conditions. It is probable that this reaction occurs in vivo and the benzene produced is rapidly converted into phenol and quinol by microsomal enzymes.

scholarly journals The metabolism of methoxyethylmercury salts

1971 ◽  
Vol 121 (3) ◽  
pp. 411-415 ◽  
Author(s):  
J. W. Daniel ◽  
J. C. Gage ◽  
P. A. Lefevre
Keyword(s):  
Carbon Dioxide ◽  
Small Proportion ◽  
Enzyme System ◽  
Inorganic Mercury ◽  
Half Time ◽  
Single Subcutaneous Dose ◽  
Subcutaneous Dose

The metabolism of methoxy[14C]ethylmercury chloride in the rat has been investigated. After a single subcutaneous dose a small proportion is excreted unchanged in urine and a larger amount in bile with some resorption from the gut. The greater part of the dose is rapidly broken down in the tissues with a half-time of about 1 day to yield ethylene and inorganic mercury. Ethylene is exhaled in the breath and the mercury migrates to the kidney and is excreted in urine. A small proportion of the dose appears as carbon dioxide in the breath and about 12% in urine as a mercury-free metabolite. It is possible that the breakdown of methoxyethylmercurychloride to ethylene and inorganic mercury is not catalysed by an enzyme system.

Biosynthesis of Nitrogenous Phospholipids in Spinach Leaves

1974 ◽  
Vol 52 (6) ◽  
pp. 469-482 ◽  
Author(s):  
M. O. Marshall ◽  
M. Kates
Keyword(s):  
Microsomal Fraction ◽  
Enzyme System ◽  
Supernatant Fraction ◽  
Exchange Reactions ◽  
Methylation Pathway ◽  
Ethanolamine Kinase ◽  
Spinach Leaves

Pathways for biosynthesis of phosphatidylserine (PS), phosphatidylethanolamine (PE), and phosphatidylcholine (PC), in spinach leaves have been studied both in vivo (whole leaves and leaf slices) and in vitro (cell-free leaf fractions). Biosynthesis of PS was shown to occur by the action of a particle-bound CDP-diglyceride: serine phosphatidyltransferase, and PE by the action of a PS-decarboxylase localized in the 100 000 × g supernatant fraction. PE was also formed by the operation of the CDP-ethanolamine:diglyceride phosphorylethanolamine transferase, localized in the microsomal fraction. The presence of ethanolamine kinase required for formation of phosphorylethanolamine was demonstrated in vitro, but not the presence of CTP:phosphorylethanolamine cytidyltransferase; however, the latter is presumed present on the basis of in vivo results. Operation of the methylation pathway for biosynthesis of PC was established in vivo, and direct methylation of phosphatidyl-N-methylethanolamine to phosphatidyl-N,N-dimethylethanolamine (PE-diMe) and of PE-diME to PC by S-adenosylmethionine was demonstrated with a particulate enzyme system localized in the microsomal fraction; direct methylation of PE itself could not be shown in this system. PC was also synthesized by the CDP-choline:diglyceride phosphorylcholine transferase system localized in the microsomal fraction. Synthesis of PE and PC by Ca2+-stimulated exchange reactions with ethanolamine and choline, respectively, could be demonstrated, but at low rates. However, no synthesis of PS by exchange reactions with serine could be detected.

scholarly journals ALTERATIONS IN BIOCHEMICAL COMPOSITION AND RIBONUCLEIC ACID METABOLISM INDUCED IN RAT LIVER BY CORTISONE

1956 ◽  
Vol 2 (3) ◽  
pp. 331-350 ◽  
Author(s):  
Charles Upton Lowe ◽  
Royden N. Rand
Keyword(s):  
Rat Liver ◽  
Biochemical Composition ◽  
Microsomal Fraction ◽  
Acid Metabolism ◽  
Chemical Constituents ◽  
Differential Centrifugation ◽  
Sucrose Solutions ◽  
The Relationship

An investigation of the effect of cortisone administration upon the chemical composition of intracellular particulates of rat liver has been made. Livers were homogenized in 0.25 M sucrose solutions and submitted to differential centrifugation. Five fractions were prepared: mitochondria (Mit), microsomes (Mi), ultracentrifugable (U), non-sedimentable (S), and nuclear (Nuc). Measurement was made of total and polymerized RNA, nitrogen, lipide P, and uptake of P32 by the RNA of each fraction. The following observations were made:— Cortisone administration caused a fall in concentration in all measured constituents except glycogen. On a per liver basis, however, total liver RNA was unchanged in amount; nitrogen content of Mi fell and that of S increased; the lipide P of Mit and Mi also decreased. The biochemical composition of a statistical mitochondrion was significantly altered; in contrast, the microsomal fraction decreased in amount, but the relationship between the chemical constituents was unchanged. When polymerized RNA was sought by a process involving precipitation from ethanol at 20°C., none was found in the Mit of cortisone livers and the amount in Mi was much less than found in the normal. When, however, precipitation was conducted at 4°C., yields of polymerized RNA in all fractions after cortisone were equal to or greater than those found in the normal. Furthermore, incubation of mixtures of homogenates from normal and cortisone livers resulted in loss of warm precipitable RNA. These data strongly suggest the presence of an enzyme in cortisone livers which upon incubation with normal livers made preparation of polymerized RNA virtually impossible by use of the warm method. This agent, thought to operate in vivo and in vitro, was not present in significant amounts in normal livers, since incubation in this instance had no effect upon the amount of polymerized RNA. Mit from cortisone livers obtained by the cold technique had a significantly decreased rate of incorporation of P32 even though the yield of RNA from this fraction was increased. To reconcile these observations, it was proposed that under the influence of cortisone a variant of normal RNA is synthesized or normal RNA is converted to this variant. This "new" RNA has new solubility properties, a new rate of incorporation of P32, and conceivably it cannot act as a template for normal protein synthesis.

REDUCED SENSITIVITY OF THE THYROID TO THYROTROPHIC HORMONE AND LATS FOLLOWING TREATMENT WITH ANTIMICROSOMAL ANTIBODIES

1973 ◽  
Vol 74 (4) ◽  
pp. 675-684
Author(s):  
J. Földes ◽  
J. Takó ◽  
Cs. Bános ◽  
E. Gesztesi ◽  
J. Juhász
Keyword(s):  
Epithelial Cells ◽  
Hashimoto’S Thyroiditis ◽  
Microsomal Fraction ◽  
Hashimoto's Thyroiditis ◽  
Thyrotrophic Hormone ◽  
Site Of Action ◽  
Enhanced Secretion ◽  
Antimicrosomal Antibody

ABSTRACT Antibodies raised against the microsomal fraction of the thyroid epithelial cells have been shown to inhibit in vitro binding of LATS to the microsomal fraction and to diminish in vivo thyroid stimulating effects of both LATS and TSH. Antimicrosomal antibody is also likely to block in vivo binding of LATS to the thyroid, and to reduce its rate of elimination from the circulating blood. The results are consistent with the assumption that the receptor structures and site of action of LATS and TSH in the thyroid are identical. On the basis of these findings the possibility arises that high titres of antimicrosomal antibodies in the serum may interfere with the results of LATS bioassay in such patients. Moreover, it seems reasonable to assume that in Hashimoto's thyroiditis high levels of antimicrosomal antibodies reduce the TSH sensitivity of thyroid, leading to an enhanced secretion of TSH and promoting the development of hypothyroidism.

In Vitro Studies on the Metabolism of Antipyrine in the Pig and Rat: with Special Refierence to Veterinary Medicine Licensing

1993 ◽  
Vol 12 (6) ◽  
pp. 537-539 ◽  
Author(s):  
Luis A. Sainz-Pardo Clares ◽  
Ian C. Shaw
Keyword(s):  
Present Report ◽  
Veterinary Drug ◽  
Target Species ◽  
Pig Liver ◽  
Experimental Procedure ◽  
Veterinary Medicines ◽  
Liver Homogenates ◽  
Product Licence

Preparation of product licence applications for veterinary medicines requires metabolic studies in the target species. This experimental procedure uses animals and is costly. In the present report of preliminary studies it is demonstrated that pig liver homogenates prepared from abattoir material and homogenates of rat liver show the interspecies metabolic differences that would be expected in vivo. The results therefore support the use of abattoir-derived liver homogenates in preliminary studies to investigate target species metabolism in veterinary drug development.

Prophylactic Effect Of Aqueous Propolis Extract Against Acute Experimental Hepatotoxicity In Vivo

2002 ◽  
Vol 57 (3-4) ◽  
pp. 379-385 ◽  
Author(s):  
Aiman S. El-Khatib ◽  
Azza M. Agha ◽  
Laila G. Mahran ◽  
Mohamed T. Khayyal
Keyword(s):  
Reduced Glutathione ◽  
Wide Spectrum ◽  
Folk Medicine ◽  
Lipid Peroxide ◽  
Isolated Hepatocytes ◽  
Propolis Extract ◽  
Single Intraperitoneal Injection ◽  
Liver Homogenates

Propolis has been extensively used in folk medicine for the management of a wide spectrum of disorders. In a previous study, we demonstrated the protective effect of the aqueous propolis extract (APE) against the injurious effects of carbon tetrachloride (CCl4) on hepatocytes in vitro. The present investigation was carried out to show whether the hepatoprotective effect of the extract could also be manifested in vivo. Rats were given APE orally for 14 consecutive days, before being subjected to a single intraperitoneal injection of CCl4. One day after the CCl4 injection, the animals were sacrificed, hepatocytes were isolated and liver homogenates were prepared for the assessment of liver injury. In isolated hepatocytes, APE afforded protection against CCl4-induced injury as manifested by a decrease in the leakage of the cytosolic enzyme lactate dehydrogenase (LDH), decreased generation of lipid peroxide and maintenance of cellular reduced glutathione (GSH) content. In principle, similar findings were observed in liver homogenates. The present findings show that APE has in vivo hepatoprotective potential which could be attributed at least in part to the maintenance of cellular GSH content. The latter effect seems to play an important role in conserving the integrity of biomembranes as it was associated with a decrease in lipid peroxidation and reduced leakage of cytosolic LDH

scholarly journals Increased oxidation of uroporphyrinogen by an inducible liver microsomal system. Possible relevance to drug-induced uroporphyria

1988 ◽  
Vol 250 (1) ◽  
pp. 161-169 ◽  
Author(s):  
F De Matteis ◽  
C Harvey ◽  
C Reed ◽  
R Hempenius
Keyword(s):  
Chick Embryo ◽  
Drug Metabolism ◽  
Microsomal Fraction ◽  
Marked Decrease ◽  
Rat Hepatocytes ◽  
Drug Induced ◽  
Dependent Mechanism ◽  
Stimulation Of

1. The hypothesis that uroporphyria-inducing drugs stimulate the oxidation of uroporphyrinogen by a microsomal NADPH-dependent mechanism was tested. 2. 3,4,3′,4′-Tetrachlorobiphenyl, a very effective inducer of uroporphyria in chick-embryo hepatocyte cultures, stimulates the NADPH-dependent oxidation of uroporphyrinogen by chick-embryo microsomal fraction in vitro. 3. Two different actions of 3,4,3′,4′-tetrachlorobiphenyl are apparently required for this effect: (a) induction of a microsomal system by treatment in vivo and (b) interaction with the induced microsomal fraction in vitro, producing an oxidizing species. 4. The analogue 2,4,2′,4′-tetrachlorobiphenyl is relatively ineffective in both the production of porphyria in culture and the stimulation of porphyrinogen oxidation in vitro. 5. Rat hepatocytes do not develop uroporphyria when treated with polychlorinated biphenyls in culture, yet they respond to these drugs with typical induction of cytochrome P-448-dependent drug metabolism. 6. These data provide support for the hypothesis of an increased oxidation of uroporphyrinogen in drug-induced uroporphyria, but also suggest that induction of cytochrome P-448 is not the only factor involved. 7. Both I and III isomers of uroporphyrin and heptacarboxylate porphyrin accumulate when chicken hepatocytes are made uroporphyric by drugs; treatment with desferrioxamine causes a marked decrease in both isomers, suggesting that iron may be involved in the accumulation of both.

scholarly journals Species differences in the metabolism and excretion of sulphasomidine and sulphamethomidine

1969 ◽  
Vol 111 (2) ◽  
pp. 173-179 ◽  
Author(s):  
J W Bridges ◽  
S R Walker ◽  
R T Williams
Keyword(s):  
Partition Coefficients ◽  
Species Differences ◽  
Species Difference ◽  
Acetyl Derivative ◽  
The Other ◽  
Main Metabolite ◽  
Monkey Liver ◽  
Liver Homogenates

1. The excretion of 2,4-dimethyl-6-sulphanilamidopyrimidine (sulphasomidine; Elkosin) and 4-methoxy-2-methyl-6-sulphanilamidopyrimidine (sulphamethomidine) given orally was examined in man, rhesus monkey, rabbit and rat. 2. About 70% of sulphasomidine (0·1g./kg.) is excreted mainly unchanged in the urine by these species in 24hr.; less than 15% of the dose is acetylated and there is no marked species difference in the fate of this drug. 3. Sulphamethomidine is excreted more slowly than sulphasomidine, and in the rat, rabbit and monkey the main metabolite is the N4-acetyl derivative. In man, only 20–30% of the dose is excreted in 24hr. and nearly 70% of this is sulphamethomidine N1-glucuronide, which is also excreted by the monkey but not by the rat or rabbit. There is therefore a marked species difference in the metabolism of sulphamethomidine. 4. Sulphamethomidine N1-glucuronide was synthesized and shown to be identical with the glucuronide isolated from monkey urine. 5. Sulphasomidine, sulphamethomidine and sulphadimethoxine (2,4-dimethoxy-6-sulphanilamidopyrimidine) were acetylated by rabbit or monkey liver homogenates. Although sulphasomidine is poorly acetylated in vivo, it is acetylated in vitro at rates comparable with those of the other two drugs. 6. The solubilities, partition coefficients and plasma-protein-binding of the drugs were measured. 7. The results are discussed.

IN VITRO INHIBITION OF SUCCINATE OXIDATION BY ALFALFA SAPONIN

1970 ◽  
Vol 50 (1) ◽  
pp. 107-112 ◽  
Author(s):  
P. R. CHEEKE ◽  
J. E. OLDFIELD
Keyword(s):  
Enzyme Activity ◽  
Cumulative Effects ◽  
Succinate Oxidation ◽  
Saponin Content ◽  
Liver Homogenates ◽  
In Vitro Inhibition ◽  
Ethanol Extracts ◽  
Reaction Vessels

The effect of various levels of alfalfa saponin on the in vitro oxidation of succinate by rat liver homogenates was examined. With levels of 1 to 30 mg saponin per 100 mg liver tissue, the degree of inhibition increased from 3 to 90%. The inhibition was noncompetitive, since it was not overcome by increasing the substrate concentration. Mitochondria isolated from homogenates which had been incubated with saponin exhibited a reduced capacity to oxidize succinate of about the same magnitude as observed when saponin was added directly to the homogenates in the reaction vessels. Since the procedure for isolation of mitochondria should remove any unbound saponin, the reduction in oxidation capacity was attributed to binding of saponin to the succinoxidase enzyme. Thus, cumulative effects of saponin on enzyme activity might occur in vivo. Ethanol extracts of alfalfa were also found to inhibit in vitro succinate oxidation. Evidence is presented indicating that the inhibitory activity of these extracts was not due to their saponin content. Possible implications of the inhibition of succinate oxidation by alfalfa saponin are discussed.

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