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Biomedical subjects

A B Makar

Publications and source records attributed to A B Makar.

At least 19 recordsLinked to original sources
PubMed1990

Formate metabolism in young swine.

Formate generated from methanol metabolism in vivo is the chemical entity responsible for the development of the methanol toxicity syndrome in the monkey. Compared to rats, monkeys are in a state of folate deficiency. This leads to a decreased ability to dispose of formate generated leading to its accumulation and the subsequent development of the classic symptoms of methanol toxicity. Rats possess a more efficient folate system; therefore, they metabolize formate very readily and do not exhibit methanol toxicity symptoms. In this report, the hepatic folate content and the ability to handle a formate "load" were evaluated in another animal species, the pig. The results obtained indicate that the pig, compared to all other species studied, has extremely low levels of folates and very low levels of a key enzyme in the folate pathway, namely 10-formyl H4folate dehydrogenase. Also the pig's ability to dispose of formate was extremely limited and slower than that observed in rats or monkeys. These results suggest that the pig may be a suitable animal model for studying formate metabolism and possibly methanol toxicity.

Animals↗
PubMed1987

The role of formate and S-adenosylmethionine in the reversal of nitrous oxide inhibition of formate oxidation in the rat.

Studies have been performed in rats in order to test whether methionine reverses the inhibition of formate oxidation produced by nitrous oxide by virtue of the conversion of methionine to formate. At a dose of methionine (100 mg/kg, 671 mumol/kg) that completely reverses the nitrous oxide inhibition of formate oxidation no significant conversion of the methyl group, carboxyl, or backbone of methionine to formate was apparent. No increases in hepatic formate levels were seen after the administration of 671 mumol/kg methionine or ethionine, and formate treatment did not alter the rate of 14CO2 formed after methionine was administered labeled in the methyl, carboxyl, or backbone position. The reversal of nitrous oxide inhibition of formate oxidation was found to correlate temporally with either S-adenosylmethionine levels after methionine administration or S-adenosylethionine levels following ethionine treatment. After methionine or ethionine administration, elevated hepatic steady state levels of tetrahydrofolate were observed and were coincident with elevated S-adenosylmethionine or S-adenosylethionine. Since formate oxidation rates are dependent on the hepatic tetrahydrofolate level, the mechanism of methionine reversal of nitrous oxide inhibition appears to be related to effects of hepatic S-adenosylmethionine which are important in maintaining and regulating tetrahydrofolate, rather than formate generation from methionine.

Adenosine↗
PubMed1983

Effect of nitrous oxide and methionine treatments on hepatic S-adenosylmethionine and methylation reactions in the rat.

Nitrous oxide administration to experimental animals leads to significant alterations in the hepatic folate pathway. This pathway is closely linked to the metabolism of methionine and S-adenosylmethionine (AdoMet), two compounds that play a central role in biologically important methylation reactions. This study was carried out to assess whether nitrous oxide administration to animals can affect the metabolism of AdoMet and the AdoMet-dependent methylation reactions. Exposure of rats to a mixture of nitrous oxide and oxygen (50:50) for 2 hr reduced hepatic AdoMet levels. However, when methionine was administered to these rats, hepatic AdoMet rapidly increased to levels that were significantly higher than those observed in air-exposed animals. Concomitant with this increase, there was a significant and marked increase in the rate of methylation of phospholipids and carboxymethylation of proteins. Thus, nitrous oxide, in addition to its inhibitory effect on 5-methyltetrahydrofolate:homocysteine methyltransferase (methionine synthase, EC 2.1.1.13) activity, possesses another effect. It increases the rate of conversion of exogenously administered methionine into AdoMet with a subsequent increase in the rate of methylation of key cellular constituents.

Animals↗
PubMed1981

Methanol poisoning and formate oxidation in nitrous oxide-treated rats.

Formic acid does not accumulate in the rat after the administration of methanol as it does in methanol-poisoned humans and monkeys. In addition, rats do not manifest the metabolic acidosis and ocular toxicity characteristic of methanol intoxication in primates. Nitrous oxide treatment was used to inhibit 5-methyltetrahydrofolate homocysteine methyltransferase (methionine synthetase, EC 4.2.99.10) in order to delineate the role of this enzyme in regulating the metabolism of formate in rats and in determining the sensitivity of this species to methanol intoxication. Nitrous oxide treatment resulted in a decrease in hepatic levels of nonmethylated tetrahydrofolate forms and an increase in 5-methyltetrahydrofolate. Rats treated with nitrous oxide exhibited a marked decrease in the rate of oxidation of formate to carbon dioxide. The rate of disappearance of formate from the blood in these animals was decreased to half the control rate. Rats treated with nitrous oxide and administered methanol accumulated formate in blood and developed metabolic acidosis. These studies support the concept of a key role of methionine synthetase in supplying the tetrahydrofolate required for the folate-dependent oxidation of formate to carbon dioxide as well as the importance of this pathway in determining the sensitivity of a species to methanol poisoning.

Amitrole↗
PubMed1980

Effect of hashish smoke on some blood and serum parameters in rabbits.

Exposure of rabbits to hashish smoke every other day for a period of one month resulted in a marked increase in blood ammonia. This increase is not probably due to any hepatic damage since there was no concomitant increase in the number of serum enzymes known to be elevated during hepatic damage. It might be related to the inhibitory effect of hashish on incorporation of amino acids into proteins resulting in an increased availability of amino acids to the catabolic pathways coupled with an increase in the glutamate dehydrogenase activity. These factors could also account for the increased blood urea concentrations in these animals.

Ammonia↗
PubMed1978

Steroidal derivatives. Part 1: some novel steroidal thiosemicarbazones. Their synthesis, anticancer and endocrinological activities.

The synthesis of several novel thiosemicarbazone derivatives of steroids, including estrogens and androgens, is described. Evaluation of the products in P 388 Lymphocytic Leukemia indicated no anticancer activity. The endocrinological screening showed that estrogenicity is slightly reduced but not abolished in the thiosemicarbazones derived from estrone-3-methyl ether (compounds 1, 2 and 4). The androgenic activity of the thiosemicarbazones derived from testosterone (compounds 7--9) was more pronounced than that of testosterone. Among the same thiosemicarbazone derivatives 7--9, only o-tolyl derivative 8 exhibited anabolic activity.

Animals↗
PubMed1977

Methyl alcohol poisoning. II. Development of a model for ocular toxicity in methyl alcohol poisoning using the rhesus monkey.

Rhesus monkeys were intoxicated with methyl alcohol, using an initial dose of 2 gm/kg and subsequent doses were administered in order to maintain an attenuated and prolonged state of intoxication. Arterial blood samples were drawn for methyl alcohol, formate, PO2, PCO2, and pH, which were monitored periodically throughout the course of the experiment. With the use of these procedures monkeys developed metabolic acidosis with the accumulation of formic acid in the blood and a corresponding decrease in blood bicarbonate. These animals served as models, which allowed for ocular evaluation for early signs related to methyl alcohol poisoning. A mechanism to explain toxicity is proposed and discussed.

Acidosis↗
PubMed1977

Methyl alcohol poisoning III. Ocular toxicity.

The ocular toxicity of methyl alcohol has been investigated in six rhesus monkeys. All the animals developed fundus changes within 43 to 171 hours after its ingestion. The only fundus lesion seen was optic disc edema and associated changes, usually of a marked degree. Fluorescein fundus angiography confirmed the findings. The retinal and choroidal circulations, including the retinal capillary bed, were normal. Ophthalmoscopically and angiographically, optic disc edema in methyl alcohol poisoning was indistinguishable from that seen in raised intracranial pressure, except that no increased intracranial pressure was observed. It is postulated that optic disc edema in methyl alcohol poisoning is due to an axoplasmic flow stasis.

Animals↗
PubMed1977

Methyl alcohol poisoning. IV. Alterations of the morphological findings of the retina and optic nerve.

The ocular morphological findings of three methyl alcohol-intoxicated rhesus monkeys with optic disc swelling was investigated with light and electron microscopy in conjunction with intravascular horse radish peroxidase. Alterations observed in the optic nerve head were confined to the axons and consisted of swelling and clustering of the mitochondria, disruption of the neurotubules, the formation of vesicles, and enlargement of the axon segments in the prelaminar region. Swelling of the oligodendroglial cytoplasm in contact with the axons and of the astrocytes was seen in the retrolaminar optic nerve and the intraorbital optic nerve. Alterations were not observed in the retina. It is hypothesized that the alterations in the axons are the result of disrupted axoplasmic flow. Possible mechanisms relating methyl alcohol intoxication to disruption of axoplasmic flow are discussed.

Animals↗
PubMed1977

Effect of some central nervous system acting drugs on rat brain and liver monoamine oxidase activity.

A number of central nervous system acting drugs were administered to male rats. At certain time intervals after the administration of these drugs, the rats were sacrificed. Liver and brain monoamine oxidase (MAO) activities were determined. The drugs employed were: ethyl alcohol, cognac, hexobarbital, diazepam, imipramine and chloralose. Results obtained indicated that the liver MAO activity was not altered by any of these drugs. Brain MAO activity, contrary to in vitro studies, was increased by alcohol and cognac. The increase was not due to a direct effect of alcohol on the enzyme activity, since the in vitro addition of equivalent concentrations of alcohol, as those calculated to be present in vivo, to brain homogenates resulted in a decrease rather than an increase in activity.

Alcoholic Beverages↗