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Biomedical subjects

M R Montgomery

Publications and source records attributed to M R Montgomery.

At least 37 records · Page 2Linked to original sources
PubMed1988

Influence of bipyridylium compounds on microsomal mixed-function oxidation activities.

The two principal bipyridyl herbicides, paraquat and diquat, were investigated for their influence on microsomal mixed-function oxidation (MFO) activities and on NADPH oxidation rates in lung, liver, and kidney preparations. In lung microsomal preparations, benzphetamine N-demethylation was found to be inhibited by paraquat and diquat in a concentration-dependent manner, but ethylmorphine N-demethylation was unaffected by these bipyridyls. In liver microsomal fractions, both benzphetamine and ethylmorphine N-demethylases were inhibited by paraquat and diquat. Neither bipyridyl affected MFO activity in kidney preparations. A kinetic investigation of the enzyme inhibition showed that only Vmax was affected by paraquat and diquat, providing the first evidence for noncompetitive inhibition by the bipyridyls. In all microsomal preparations, NADPH oxidation was stimulated significantly by paraquat and to an even greater extent by diquat in the absence or presence of benzphetamine or ethylmorphine. The influence of MFO substrates on the stimulation varied widely among the three organ systems. In lung, paraquat- or diquat-mediated stimulation of NADPH oxidation was equal in the absence of MFO substrates and in the presence of ethylmorphine, but the stimulation was increased in the presence of benzphetamine. Stimulation of NADPH oxidation by the bipyridyls, in liver as well as in kidney preparations, was equal in all situations in the absence of MFO substrates and in the presence of benzphetamine or ethylmorphine, although the quantity of this stimulation was greater in liver than in kidney fractions. It is apparent that the bipyridyls are potent stimulators of in vitro NADPH oxidation in microsomal preparations from several organs. The quantity of the NADPH oxidation stimulation seems to be a decisive factor in the inhibition of xenobiotic metabolism. Whether the stimulation of NADPH oxidation and the non-competitive inhibition of xenobiotic metabolism play a significant role in bipyridyl toxicity are under further investigation.

Animals↗
PubMed1988

Artifacts in the determination of microsomal xenobiotic N-demethylation in the presence of ascorbic acid tris buffer and Nash reagent.

1. During investigation of microsomal xenobiotic N-demethylation in the presence of ascorbic acid, large increases in apparent enzymic activity were observed. 2. Examination of incubation components indicated that a non-enzymic interaction between ascorbic acid and Tris buffer, in the presence of acetylacetone and ammonium acetate (Nash reagent), was occurring. 3. The resulting chromophore had an absorption maximum at 412 nm that coincided with the absorption for the chromophore resulting from the interaction of the Nash reagent with the product (formaldehyde) of the enzymic reaction. 4. Strict controls of ascorbic acid potential chemical interaction with incubation components are required in enzymic studies.

Acetates↗
PubMed1988

Ozone-induced lamellar body responses in a rat model for alveolar injury and repair.

Exposure of adult rats to 3 ppm ozone for 8 hours results in diffuse alveolar damage with well-defined sequential stages of bronchiolo-alveolar injury and repair. This model is characterized by acute pulmonary edema showing high concentration of lavage fluid protein that is maximally elevated at 24 hours with return to control level at recovery (96 hours). Using techniques that enable optimal preservation of lamellar body ultrastructure, it was demonstrated morphometrically that expansion of the vacuolated lamellar body (LB) compartment is an early, transient LB response of the type II cell to acute injury. This change appears to be initiated by increased LB secretion. The reparative stage, 24-48 hours postexposure, begins with hypertrophy rather than hyperplasia of many type II cells, resulting in a 3-fold increase of mean type II cell volume at 48 hours. During this stage there is also significant expansion of the total LB compartment with corresponding increased LB storage of surfactant disaturated phosphatidylcholine (DSPC) per type II cell. At recovery, 96 hours, the lungs contained twice the normal numbers of type II cells, but the total size of lamellar body compartment per type II cell as well as the DSPC content of the isolated lamellar body pool returned to normal levels. In contrast, accumulating surfactant DSPC in lavage fluid increased progressively throughout the reparative and recovery stages presumably due in part to parallel increase in type II cell numbers at 48 and 96 hours. Additional changes of surfactant included abnormal secretion of densely coiled lamellar bodies that accumulated in alveolar spaces at the expense of tubular myelin. These observations indicate that acute oxidant injury to alveoli initiates progressive hypertrophy followed by hyperplasia of type II cells, in association with sequential development of characteristic lamellar body changes leading to increased storage and secretion of surfactant with reduced ability to form tubular myelin.

Animals↗
PubMed1987

Selective inhibition of bipyridyl-stimulated NADPH oxidation by ascorbic acid.

The effect of the bipyridyl herbicides, paraquat and diquat (0.01-1.0 mM), on NADPH oxidation was determined in vitro using rat lung microsomal preparations. Experiments were performed in the absence of mixed function oxidation (MFO) substrates, in the presence of substrates (ethylmorphine or benzphetamine), and also in the presence of ascorbic acid (0.1-10.0 mM). NADPH oxidation was stimulated by both herbicides in the absence or presence of either substrate in a concentration-dependent manner. When ascorbic acid was included in incubations along with either bipyridyl, the stimulated rate of NADPH oxidation decreased in the presence of benzphetamine but the stimulation was unaltered in the presence of ethylmorphine or in the absence of substrate. These studies indicate that ascorbic acid may offer some protection from bipyridyl-mediated NADPH oxidation in rat lung microsomal fractions, but that protection appears to be dependent upon the simultaneous presence of specific MFO substrates.

Animals↗
PubMed1987

Age-related difference in pulmonary response to ozone.

Acute exposure to 1.5 ppm O3 produced different responses in adult and aged rat lungs. Total triphosphonucleotides were only slightly decreased in adult animals, but were markedly decreased in aged animals. Also, adult animals maintained a greater proportion of their available triphosphonucleotides in the reduced form (NADPH) compared to aged animals. These results suggest that aged animals may not be able to maintain pulmonary reducing equivalents as efficiently as adult animals in the face of an oxidant insult.

Aging↗
PubMed1987

Species differences in lung mitochondrial monoamine oxidase activities.

Pulmonary mitochondrial monoamine oxidase (MAO) activity was examined in preparations from rat, rabbit and guinea-pig with 12 different amines as substrates: serotonin, norepinephrine, and octopamine (type A specific); tryptamine, benzylamine, 5-methoxytryptamine, 5-methyltryptamine, p-methoxyphenylethylamine, and 3,4-dimethoxyphenethylamine (type B specific); and tyramine, dopamine and 3-methoxytyramine (type A + B specific). The oxidation of type A and type A + B substrates was greater in guinea-pig lung mitochondria than in rat or rabbit preparations. Except for benzylamine, the oxidation of type B substrates was similar in all three species. Benzylamine was not oxidized by guinea-pig lung mitochondria but was actively metabolized by rat and rabbit preparations.

Animals↗
PubMed1986

Mitochondrial alterations in the brain of the rat caused by chlorphentermine.

The effects of chlorphentermine on the bioenergetics and activity of monoamine oxidase in mitochondria from the brain of the rat were examined. Oxidation rates of glutamate and succinate were investigated in the presence of chlorphentermine (0.1-5.0 mM). In small concentrations (0.1-1.0 mM), chlorphentermine decreased the respiratory control ratio and the adenosine diphosphate oxygen (ADP/O) ratio, and stimulated state four respiration. State three respiration and the uncoupled state were also decreased, but to a lesser degree. In the presence of larger concentrations of chlorphentermine (1.0-5.0 mM), the respiration in states four, three, and in the uncoupled state, as well as the respiratory control ratio and ADP/O ratio, were decreased significantly. These data indicate that chlorphentermine functions as an uncoupler of oxidative phosphorylation. Oxidation of norepinephrine, serotonin, octopamine, tyramine and dopamine by monoamine oxidase (MAO), an enzyme marker of the outer mitochondrial membrane, was inhibited in the presence of 0.01 to 0.1 mM of chlorphentermine. Oxidation of tryptamine and benzylamine was unaffected. A kinetic study of the oxidation of serotonin in the absence and presence of chlorphentermine (0.025-0.1 mM) indicated that both the Vmax and Km were affected. This drug is an inhibitor of monoamine oxidase of mitochondria of the brain with mixed type inhibition. These combined data show that chlorphentermine affects biochemical processes in both inner and outer mitochondrial membranes.

Animals↗
PubMed1986

Glucose ameliorates the depletion of NADPH by paraquat in rat lung slices.

Paraquat-stimulated NADPH depletion in rat lung slices is responsive to exogenous glucose concentration. Lung slices incubated with 11 mM glucose and 10(-4) M paraquat had a 40% lower NADPH/NADP+ ratio than did control lung slices. Incubation with no added glucose and 10(-5) M paraquat caused a 41% decrease in NADPH/NADP+. With paraquat at 10(-5) M, glucose at 1.1, 5.5, 11, or 22 mM increased NADPH/NADP+ ratios in a concentration-dependent manner until, at 22 mM glucose, the effect of paraquat was prevented. The sum of NADP+ plus NADPH was only 60% of control with 10(-5) M paraquat and no glucose. However, with any concentration of glucose from 1.1 to 22 mM, the total was 92% of control. The results indicate that glucose may be beneficial in preventing paraquat-mediated NADPH depletion in rat lung slices.

Animals↗
PubMed1986

Child health, breast-feeding, and survival in Malaysia: a random-effects logit approach.

This study examines the possibility that estimation of the effect of breast-feeding on infant survival is affected by selection bias, in that children who are healthier at birth may be more likely to be breast-fed. Data are from the 1976 Malaysian Family Life Survey. "Ordinary logit models for breast-feeding and survival are estimated, and the results suggest that selection is indeed present. For example, children of higher birth weight appear to be more likely to be breast-fed and likely to survive. In addition, weight at birth and the duration of breast-feeding appear to be linked." Using birth weight as an indicator for the child's health, the authors conclude that "the direct influence of breast-feeding on survival remains of overwhelming importance even after corrections for selection bias are made."

Asia↗
PubMed1985

Chlorphentermine inhibits pulmonary mitochondrial monoamine oxidase.

Oxidation of six amine substrates by rat, rabbit and guinea-pig lung mitochondrial monoamine oxidase (MAO) was investigated polarographically with a Clark oxygen electrode in the presence of chlorphentermine (CP). This amphiphilic drug decreased the deamination of serotonin, norepinephrine, tyramine and dopamine significantly in all three species. However, the oxidation of tryptamine and benzylamine was unchanged. Amine oxidation by MAO in guinea-pig lung mitochondria was much more sensitive to the CP-mediated inhibition than rat or rabbit. A kinetic study of serotonin oxidation in the absence and presence of CP showed that both Vmax and Km were affected. These combined data indicate that CP is a specific inhibitor of pulmonary, mitochondrial monoamine oxidase form A with mixed-type inhibition.

Animals↗
PubMed1985

Chlorphentermine-induced biochemical alterations in mitochondrial membranes.

The effects of chlorphentermine (CP) on bioenergetics and monoamine oxidase activity in rat liver mitochondria were examined. Oxidation rates of isocitrate, glutamate and succinate were investigated in the presence of CP (0.5-5.0 mM). In the presence of low concentrations (0.5-2.0 mM) CP decreased respiratory control ratio and ADP/O ratio, and stimulated state 4 respiration. State 3 respiration and uncoupled state were unaffected. The same pattern of changes was found after in vivo CP treatment for 1 or 2 weeks (30 mg/kg i.p., 5 days/week). CP also increased respiration in state 3 that had been inhibited previously by oligomycin. These data indicate that CP functions as an uncoupler of oxidative phosphorylation. In the presence of higher concentrations of CP (3.0-5.0 mM), respiration in states 4, 3 and in uncoupled state, as well as respiratory control ratio and ADP/O, were decreased. Oxidation of norepinephrine, serotonin, tyramine and dopamine by monoamine oxidase, an enzyme marker of the outer mitochondrial membrane, was inhibited in the presence of 0.05 to 0.5 mM CP. Tryptamine and benzylamine oxidation was unaffected. A kinetic study of serotonin oxidation in the absence and presence of CP (0.05-0.25 mM) indicated that both the Vmax and Km were affected. This drug is an inhibitor of liver mitochondrial monoamine oxidase with mixed-type inhibition. These combined data show that CP affects biochemical processes in both inner and outer mitochondrial membranes.

Animals↗
PubMed1984

Ascorbic acid nutritional status does not affect the biochemical response to paraquat.

Guinea pigs were subjected to dietary control of ascorbic acid intake to produce deficient, normal, and supplemented tissue ascorbate concentrations. Paraquat, a potent pulmonary toxin, was then administered. Tissue distribution and covalent binding of paraquat were not affected significantly by ascorbate nutritional status except for decreased 24-hr kidney burdens in deficient animals. Paraquat increased pulmonary thiobarbituric acid reactivity and mixed disulfide formation, but no evidence of either a protective or a potentiative interaction of endogenous ascorbate and paraquat was observed. This study indicates that alteration of endogenous ascorbic acid levels does not alter the biochemical response to paraquat.

Analysis of Variance↗
PubMed1984

Alterations in monoamine oxidase activity after single and repeated exposure of rats to chlorphentermine.

Monoamine oxidase (MAO) activity was determined in rat tissues following in vivo treatments with chlorphentermine (CP). Oxidation of seven amine substrates by liver, lung or brain mitochondrial MAO was investigated at 2 h after a single i.p. injection (60 mg/kg) or after repeated injection (once daily for 3 days, 20 mg/kg, i.p.). Deamination of the type A substrates, norepinephrine, serotonin and octopamine, was decreased significantly in liver, lung and brain after both single and repeated injections. Oxidative deamination of tyramine and dopamine (type A + B substrates) was also lowered in all organs after single and repeated exposure to CP, but to a lesser degree than the type A substrates. However, oxidation of the type B substrates, benzylamine and tryptamine, was unaffected by CP administration in comparison to control. These data indicate that CP is a specific inhibitor of mitochondrial MAO, form A.

Amines↗
PubMed1984

Ascorbic acid potentiates the substrate-specific inhibition of mixed-function oxidation and the stimulation of NADPH oxidation caused by paraquat.

Paraquat inhibits the in vitro hepatic microsomal metabolism of both ethylmorphine and aniline. Inclusion of ascorbate with paraquat in the incubations did not alter the paraquat effect on ethylmorphine N-demethylase activity but potentiated the inhibition of aniline p-hydroxylase activity. Ascorbate alone was without effect on the metabolism of either substrate. Paraquat stimulated the hepatic microsomal oxidation of nicotinamide adenine dinucleotide phosphate (NADPH) equally in the absence of mixed-function oxidase (MFO) substrates or in the presence of ethylmorphine; in the presence of aniline the rate of NADPH oxidation was significantly greater. Also, in the presence of aniline, ascorbate potentiated the paraquat-induced NADPH oxidation, while it was ineffective with paraquat on NADPH oxidation in the presence of ethylmorphine or in the absence of substrates for the microsomal MFO system. The potentiated inhibition of aniline metabolism, concomitant with the potentiated stimulation of NADPH oxidation, was consistent whether liver microsomal fractions were prepared from control rats or from animals induced with phenobarbital. Investigation of possible influences on NADPH cytochrome c reductase activity was precluded by the rapid nonenzymatic reduction of cytochrome c by ascorbate. The paraquat-ascorbate redox couple would not reduce cytochrome P-450. These data suggest that a paraquat interaction with the active microsomal MFO enzyme system plays a role in the depletion of cellular NADPH stores that occurs after paraquat administration in vivo. This mechanism may play a significant role in the development of paraquat toxicity and in the potentiated toxicity observed with ascorbate and paraquat.

Aniline Hydroxylase↗