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Biomedical subjects

A R Jones

Publications and source records attributed to A R Jones.

At least 127 records · Page 7Linked to original sources
PubMed1981

The fate of oxalic acid in the Wistar rat.

1. An established procedure for determining oxalate in human urine has been modified for rat urine. The daily excretion of oxalate by the male Wistar rat is 570-650 microgram. 2. Oxalate excretion in rat urine following i.p. administration of [14C]oxalic acid (1-70 mg/kg) has been studied. The rate and degree of excretion are dose-dependent. 3. The excretion of urinary oxalate by the rat has been quantified after administration of two oxalate-producing xenobiotics, alpha-chlorohydrin and 1,2-dibromo-3-chloropropane. 4. Oxalate inhibits the metabolism of glucose and lactate by isolated rat kidney tubules in vitro.

Animals↗
PubMed1981

The metabolism of 1,3-dibromopropane by the rat.

1. The metabolism of 1,3-dibromopropane had been investigated in the rat. Two conjugated metabolites have been isolated from the urine and identified as S-(3-hydroxypropyl)cysteine and N-acetyl-S-(3-hydroxypropyl)cysteine. 2. An oxidation product, identified as beta-bromolactic acid, has been isolated as a urinary metabolite. 3. 1,3-dibromopropane is not excreted unchanged in expired air or in the urine. Approx. 15% of the dose (100 mg/kg) is excreted as metabolic products over 50 h and 3.5% as CO2 within 6 h, indicating that oxidation is the main route of detoxication.

Amino Acids↗
PubMed1981

The comparative metabolism of 2-bromoethanol and ethylene oxide in the rat.

1. The metabolism of 2-bromo[U-14C]ethanol an [U-14C]ethylene oxide has been studied in the rat. 2. As both compounds give rise to similar amounts of two urinary metabolites, identified as S-(2-hydroxyethyl)cysteine and N-acetyl-S-(2-hydroxyethyl)cysteine, it is proposed that 2-bromoethanol is converted into ethylene oxide in vivo. 3. A minor metabolite of 2-bromoethanol has been identified as N-acetyl-S-(carboxymethyl)cysteine. 4. The metabolism of bromoacetaldehyde and bromoacetic acid has been investigated; N-acetyl-S-(carboxymethyl)cysteine had been shown to be a common urinary metabolite. 5. An oxidative metabolic pathway is proposed for 2-bromoethanol, via bromoacetaldehyde and bromoacetic acid, to N-acetyl-S-(carboxymethyl)cysteine.

Amino Acids↗
PubMed1980

Inhibition of glycolysis in boar sperm by alpha-chlorohydrin.

The effect of alpha-chlorohydrin (3-chloropropan-1,2-diol) on the metabolism of D-[U-14C]-fructose and L-[U-14C]-lactate by washed boar sperm has been investigated. Whereas alpha-chlorohydrin at concentrations as low as 0.1 mM inhibited the metabolism of fructose and led to an increase in the utilization of endogenous lactate, amounts up to 500 mM had no effect on the oxidation of added lactate. Low levels of alpha-chlorohydrin increased the cellular concentrations of fructose-1,6-bisphosphate and the triosephosphates, an effect consistent with the inhibition of glyceraldehyde-3-phosphate dehydrogenase. Although [U-14C]-glycerol was rapidly oxidized by boar sperm, [U-14C]-alpha-chlorohydrin was not metabolized to 14CO2, showing that it is not converted to glycerol. Extracts obtained by sonication of boar sperm after incubation with [3-36C1]-alpha-chlorohydrin, did not contain [3-36C1]-alpha-chlorohydrin-1-phosphate. This is contrary to the postulate that this phosphorylated compound is the inhibitory metabolite of alpha-chlorohydrin.

Animals↗
PubMed1980

Blood donor protection.

The quality of blood donated or purchased may be not only inferior from a recipient or user point of view, but donation may also be injurious to the health of the donor. A study of 1215 paid donors suggests that the current screening guidelines for all donors may not be adequate. More extensive haematological study of these donors shows that abnormalities of individual haematological parameters may range from 4.3% to as high as 29.5% deending on the donor population and the quality of the screening examination. The study concludes that the donor should be better protected.

Adult↗
PubMed1980

Metabolism of three active analogues of the male antifertility agent alpha-chlorohydrin in the rat.

1. Two ketal derivatives of alpha-chlorohydrin, which possess male antifertility activity, have been synthesized labelled with 36Cl. Both are metabolized by the rat to beta-chloroacetic acid. 2. Neither derivative inhibited the glycolytic enzymes glyceraldehyde 3-phosphate dehydrogenase and triosephosphate isomerase. 3. The epoxide glycidol is metabolized to beta-chlorolactic acid, presumably by first being converted to alpha-chlorohydrin. 4. It is proposed that the male antifertility actions of these three analogues is due to their biotransformation to alpha-chlorohydrin, which is then metabolized within mature sperm to a compound which is an inhibitor of glycolysis.

Animals↗
PubMed1980

The fate of S-propylcysteine in the rat.

1. The metabolism of S-propylcysteine in the rat has been re-investigated. The previously known major metabolite has been isolated and identified as the mercapturic acid, N-acetyl-S-propylcysteine. 2. Several further metabolites have been isolated from the urine of rats treated with S-propyl[35S]cysteine. These have been identified as S-propylcysteine-S-oxide, N-acetyl-S-(2-hydroxypropyl)cysteine, S-(propylthio)lactate, S-(2,3-dihydroxypropyl)cysteine and N-acetyl-S-(2-carboxyethyl)cysteine. 3. The metabolism of S-(2-hydroxypropyl)-, S-(3-hydroxypropyl)- and S-(2,3-dihydroxypropyl)-[35S]cysteine have been investigated in the rat. The results, integrated with those from the metabolism of S-propyl[35S]cysteine, have enabled the pathways of S-propylcysteine to be deduced. 4. The oxidative metabolism of a number of S-alkyl cysteines is discussed.

Animals↗
PubMed1980

1,2-Dichloropropane: metabolism and fate in the rat.

1. The metabolism of 1,2-dichloropropane in the rat has been investigated. The major urinary metabolite has been isolated and identified as N-acetyl-S-(2-hydroxypropyl)cysteine. Two minor metabolites of 1,2-dichloropropane have been identified as beta-chlorolactate and N-acetyl-S-(2,3-dihydroxypropyl)cysteine. 2. The fate of 1-chloro-2-hydroxypropane, a proposed intermediate metabolite of 1,2-dichloropropane, has been investigated. Apart from its known urinary metabolite, N-acetyl-S-(2-hydroxypropyl)cysteine, two oxidative metabolites were detected. These were identified as beta-chlorolactaldehyde and beta-chlorolactate. 3. A pathway is proposed for the metabolism and fate of 1,2-dichloropropane in the rat. This accounts for previous observations made for the fate of radioactivity from administration of 1,2-dichloro[1-14C]propane. 4. The microbial and mammalian metabolism of several halogen-containing foreign compounds is discussed.

Acetylcysteine↗
PubMed1979

The metabolism of the soil fumigant 1,2-dibromo-3-chloropropane in the rat.

The soil fumigant 1,2-dibromo-3-chloropropane (I) undergoes hydrolysis in the rat to a series of epoxide metabolites. Alkylation of glutathione by these epoxides produces 2 urinary metabolites identified as the mercapturic acids VI (R=COCH3) and VII (R-COCH3). Hydrolysis of the epoxides produces the male antifertility agents alpha-chlorohydrin (IX, X-Cl) and alpha-bromohydrin (IX, X-Br) which are oxidatively metabolized to oxalic acid (XII), thus causing renal damage. These metabolic pathways can explain the toxic nature of the fumigant as a carcinogen, a male chemosterilant and as an agent causing kidney damage.

Animals↗
PubMed1979

Effects of glycine administration on canine experimental spinal spasticity and the levels of glycine, glutamate, and aspartate in the lumbar spinal cord.

Twelve female mongrel dogs were made paraplegic by midthoracic spinal cord transection. Beginning at 9 weeks posttransection, either glycine (50 mg/kg) or saline was injected intramuscularly each day and the signs of spinal spasticity were assessed clinically. After treating the dogs for 3 weeks, we removed the lumbar enlargement of each dog and microdissected it into gray and white areas which we assayed for glycine, glutamate, and aspartate content. Some of the clinical signs of spasticity improved in the animals injected with glycine compared to the saline-injected controls. The content of glycine was significantly elevated in the central gray matter and ventral medial white matter of the glycine-treated dogs. The levels of glutamate were also significantly elevated in the central, lateral ventral, and medial ventral gray matter and in the dorsal lateral and ventral medial white matter of the glycine-treated dogs. The possible role of these segmental putative neurotransmitters in spinal spasticity is discussed.

Animals↗
PubMed1979

The metabolism of 3-amino-1-chloropropan-2-ol in relation to its antifertility activity in male rats.

1. The metabolism of 3-amino[36Cl]chloropropan-2-ol (III) was studied in male rats. Three urinary metabolites were isolated and identified as alpha-chlorohydrin (I), beta-chlorolactic acid (V) and oxalic acid (VI). Much of the administered aminochloropropanol was excreted unchanged in the urine; 63% within 72 h, 75% over 250 h. 2. Monoamine oxidase is capable of converting aminochloropropanol to beta-chlorolactaldehyde (IV) which, by processes of either reduction or oxidation, suggests that the metabolic pathway is IV leads to I and IV leads to V leads to VI. 3. As assessed by the diuretic activities of the isomers of aminochloropropanol, oxalate appears to be produced by the (+)-isomer but not by the (-)-isomer. A difference in metabolic rate or route of the isomers may account for their differing physiological activities. 4. (+)- and (-)-aminochloropropanol exhibited identical in vitro inhibitory activities on the glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase and triosephosphate isomerase, and were substrates for monoamine oxidase to equivalent extents.

Animals↗
PubMed1979

Epoxides as obligatory intermediates in the metabolism of alpha-halohydrins.

1. The metabolism of several dihalopropanols has been studied in the rat. Irrespective of their structure, each compound produced the same two mercapturic acids, excreted as urinary metabolites. 2. The mercapturic acid metabolites of the dihalopropanols were identified as N-acetyl-S-(2,3-dihydroxypropyl)cysteine and N,N'-bis-acetyl-S,S'-(1,3-bis-cysteinyl)propan-2-ol. Depending on the halogen present, each dihalopropanol produced beta-chlorolactate or beta-bromolactate as oxidative metabolites. 3. From the metabolic pathway of these compounds, it is inferred that an epoxide is an intermediate in their metabolism. 4. The metabolism of 2-chloropropane-1,3-diol has been investigated in the rat and the isolation of one mercapturic acid, N-acetyl-S-(2,3-dihydroxypropyl)cysteine, confirms that an epoxide intermediate is involved.

Alcohols↗
PubMed1979

The oxidative metabolism of 1-bromopropane in the rat.

1. The metabolism of 1-bromopropane in the rat has been re-investigated. The previously known metabolites have been isolated and confirmed as the three mercapturic acids N-acetyl-S-propyl cysteine, N-acetyl-S-propyl cysteine-S-oxide and N-acetyl-S-(2-hydroxypropyl)cysteine. 2. Three further metabolites have been isolated from the urine of rats treated with 4-bromopropane. These have been identified as 3-bromopropionic acid and the mercapturic acids N-acetyl-S-(3-hydroxypropyl)cysteine and N-acetyl-S-(2-carboxyethyl)cysteine. 3. The metabolites of 3-bromopropanol and 3-chloropropanol in the rat have been shown to be the mercapturic acids N-acetyl-S-(3-hydroxypropyl)cysteine and N-acetyl-S-(2-carboxyethyl)cysteine and the corresponding 2-carboxyethyl halide. 4. Studies with 1-bromopropane and the 3-halopropanols in vitro indicate that oxidation of C3 and C2 of 1-bromopropane occurs before conjugation of the alkyl group with glutathione. The implications of these studies are discussed in relation to the mechanism of the biosynthesis of the S-(2-hydroxyalkyl)mercapturic acid metabolites derived from the alkyl halides.

Acetylcysteine↗