Effect of some pyrimidine compounds on rat brain monoamine oxidase-B in vitro

The effects of some pyrimidine compounds (PCs) including barbituric acid (BA) 5,5-diethyl barbituric acid (DEBA), 2-thiobarbituric acid (TBA), violuric acid (VA), 2-thiouracil (TU), and 6-amino-2-thiouracil (ATU) on the activity of rat brain monoamine oxidase-B (MAO-B) were investigated. The results revealed that MAO-B was activated by BA, DEBA, TBA, TU, and ATU, and the activation was structural, concentration, and time dependent. However, MAO-B was inhibited by VA in a noncompetitive and irreversible manner with an enzyme?Cinhibitor dissociation constant (K _i value) of 32?nM and IC₅₀ equals to 19?nM. All the studied PCs changed both the optimum pH and temperature of MAO-B.     

Effect of benzamide derivatives on rat brain monoamine oxidase activity in vitro

The ability of moclobamide and other benzamide derivatives to inhibit the activity of monoamine oxidase in the rat brain was studied. Distinct effects of these compounds on the deamination of serotonin and norepinephrine (MAO-A substrates); 2-phenylethylamine (selective MAO-B substrate); tyramine and dopamine (MAO-A and MAO-B substrates) are shown. It was demonstrated that among all the compounds studied moclobamide appeared to be the most active and selective inhibitor of MAO-A: at a concentration of 100 microM it caused a 100% inhibition of serotonin and norepinephrine deamination, which might be explained by the presence of C1 atom in the para-position of benzene ring in moclobamide molecule. Other benzamide derivatives were less active in inhibiting MAO-A and had but a negligible effect on dopamine- and 2-phenylethylamine deamination.     

Effect of adafenoxate on different rat brain structures monoamine oxidase activity in vitro

1. The effect of the nootropic drug adafenoxate on monoamine oxidase (MAO) activity in rat brain cortex, striatum, hypothalamus and hippocampus has been studied using the following substrates: tyramine (total MAO), serotonin (MAO A) and beta-phenylethylamine (MAO B). 2. In a series of increased concentrations (from 5 x 10(-4) up to 1 x 10(-5) M) adafenoxate inhibits total MAO, MAO A and MAO B in the brain structures studied. 3. The adafenoxate IC50 values obtained illustrate its inhibitory properties and its lack of selectivity toward MAO in the brain structures isolated. 4. The results of our research prove the participation of MAO in the mechanisms through which adafenoxate affects the brain monoaminergic systems and realises its central effects.     

Increase of monoamine oxidase-B activity in the brain of scrapie-infected hamsters

In the present study, the purpose is to determine activities of monoamine oxidases (MAO) in the brain of 263K scrapie-infected hamsters during the development of this experimental prion disease. Indeed, MAO activity modifications which have already been related in aging and neurodegenerations is suspected to be involved in the neuron loss process by elevated hydrogen peroxide formation. Monoamine oxidase type A (MAO-A) and B (MAO-B) activities were followed in the brain at different stages of the disease. MAO-A activity did not change significantly during the evolution of the disease. However, concerning the MAO-B activity, a significant increase was observed from 50 days post-infection and through the course of the disease and reached 42.9+/-5.3% at its ultimate stage. Regarding these results, MAO-B could be a potential therapeutic target then we have performed a pre-clinical treatment with irreversible (Selegiline or L-deprenyl) or and reversible (MS-9510) MAO-B inhibitors used alone or in association with an anti-scrapie drug such as MS-8209, an amphotericin B derivative. Our results show that none of the MAO-B inhibitors used was able to delay the onset of the disease. Neither these MAO-B inhibitors nor R-NMDA inhibitors (MK-801) can enhance the effects of MS-8209. The present findings clearly indicate a significant increase of cerebral MAO-B activity in scrapie-infected hamsters. Furthermore, inhibitors of MAO-B do not have any curative or palliative effect on this experimental model indicating that the raise of this activity is probably more a consequence rather than a causal event of the neurodegenerative process.     

In vitro andin vivo effect of organophosphate pesticides on monoamine oxidase activity in rat brain

The effects of some organophosphate pesticides, e.g. lebaycid, metacid and metasystox on the monoamine oxidase (MAO) activity in rat brain mitochondria have been studied. These pesticides cause significant inhibition of MAO activityin vitro but have negligible effects on its activityin vivo.     

Effect of neurocatin on the activity of monoamine oxidase B in rat brain synaptosomes

Neurocatin, a small (about 2,000 Dalton) neuroregulator isolated from mammalian brain, is a powerful effector of monoamine oxidase B in rat brain synaptosomes. Incubation of intact synaptosomes with neurocatin caused an inhibition of the enzyme dependent on the concentration of neurocatin. This inhibition became statistically significant at a neurocatin concentration of 10 ng/200 l and was significant at all higher neurocatin concentrations. At 40 ng/200 l, neurocatin inhibited monoamine oxidase B activity by about 60%. This inhibitory effect was almost completely abolished by breaking the synaptosomal membrane by hypotonic buffer prior to incubation with neurocatin. In addition, incubation of the synaptosomes in calcium free medium almost completely abolished the inhibitory effect of neurocatin on monoamine oxidase B. The inhibition appeared to involve covalent modification of the enzyme mediated by a neurocatin receptor(s). Measurements of the kinetic parameters of the enzyme showed that 20 ng of neurocatin caused a statistically significant decrease in V_max (by 20%) with no significant change in K_M, compared to controls. Inhibition of monoamine oxidase by neurocatin is potentially of great clinical importance because this enzyme plays a major role in catabolism of the biogenic amines and alterations in its activity is believed to contribute to several neurological disorders.     

Imipramine inhibits monoamine oxidase activity in hyperglycemic rat brain

The effect of the chronic treatment of tricyclic antidepressants like Imipramine on the catecholamine metabolism of rat brain, in normal and hyperglycemic conditions was investigated. Imipramine was found to elevate the catecholamine levels in controls, while chronic treatment of hyperglycemic animals with the drug, failed to cause any change other than seen as a result of hyperglycemia. The activities of Monoamine oxidase on the other hand, decreases significantly as a result of the treatment, both in controls and in the hyperglycemic state. The results suggest that the drug apart from acting as an antidepressant, assumes the role of a monoamine oxidase inhibitor under pathological conditions.     

Effect of prolonged cold exposure on monoamine oxidase activity and kinetics and on serotonin metabolism in the rat brain

Effects of long-term cold exposure on the content of serotonin and its metabolite 5-hydroxyindolacetic acid (5-HIAA) and monoamine oxidase (MAO) activity and kinetic parameters (Km and Vmax) of oxidative deamination of serotonin in rat brain stem. The increase of 5-HIAA level in the initial period of chronic cold exposure was determined by the blockade of active metabolite transport from the brain. The level of serotonin and the rate of its catalytic deamination by MAO were found to be decreased in cold-adapted rats. The magnitude of the Km of serotonin deamination was unchanged.     

In vitro andin vivo effect of chloropromazine,imipramine and lithium chloride on monoamine oxidase activity in rat brain mitochondria

Chloropromazine (CPZ) and imipramine at a concentration of 1×10^–3 M inhibit rat brain mitochondrial monoamine oxidase activity in vitro by 70 and 55% respectively, while lithium, even at a concentration of 0.05 M, inhibits the activity of this enzyme very negligibly (4%). In vivo, these drugs at a dose level of 56 mg CPZ, 76 mg Jimipramine and 76 mg lithium chloride/Kg body wt., did not cause any observable variation from normal in brain mitochondrial monoamine oxidase activity.To whom correspondence should be addressed.     

Influence of age on brain vascular and cardiovascular monoamine oxidase activity in the rat

Monoamine oxidase (MAO) activity in brain microvessels and cardiovascular tissues was examined in rats of different age. MAO activity continued to increase with age in the heart, but in contrast, reached maximum activity in three weeks in the aorta, mesenteric artery and mesenteric vein. Between 7 and 60 weeks, there was a small decline in the MAO activity in the testicular artery. The highest MAO activity was found in the cerebral microvessels and increased with age. The half-life of MAO was estimated in the heart and peripheral blood vessels in young and old animals. The half-life of cardiac MAO was increased with age whereas that of the mesenteric vein, mesenteric artery and aorta remained constant between 7 and 112 weeks. Thus an explanation for this increased cardiac MAO activity in old rats was a reduced rate of degredation of this enzyme. The high activity of the enzyme in the brain microvessels suggests that it may participate in regulating the influx and efflux of monoamines in the central nervous system.     

Effect of heat exposure on the activity of monoamine oxidase in the rat brain and interscapular brown adipose tissue

The exposure of Wistar male rats (200±20 g) to high ambient temperature (38°C) for 20 and 60 min induced an equal decrease in hypothalamic, brain stem and hippocampal monoamine oxidase activity when compared to controls. The interscapular brown adipose tissue monoamine oxidase activity, as well as oxygen consumption and rectal temperature were increased only after a 60 min heat exposure. The adrenal function, assessed by dopamine-beta-hydroxylase activity and cholesterol concentration, was enhanced both after 20 and 60 min. In conclusion, heat induced the increase in adrenal function and interscapular brown adipose tissue monoamine oxidase activity, but the decrease in that of the brain.     

Effect of chronic administration of phenytoin on regional monoamine levels in rat brain

Phenytoin (DPH) is a widely used anticonvulsant drug but a conclusive mode of action is not yet clear. This study was undertaken to assess the effects of chronic administration of DPH on monoamine levels. DPH (50 mg/kg body weight) was administered to adult male Wistar rats by intraperitoneal injections for 45 days and the regional brain levels of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) were assayed using high performance liquid chromatographic (HPLC) method. The experimental rats revealed no behavioral deficits of any kind nor body and brain weight deficits were observed. Increased NE levels were observed after DPH administration in motor cortex (P<0.05), striatum-accumbens (P<0.01) and hippocampus (P<0.01), whereas, NE level was decreased in brain stem (P<0.05). DA levels were increased in striatum-accumbens (P<0.05), hypothalamus (P<0.001) and cerebellum (P<0.001) but decreased in brainstem (P<0.01). In DPH treated rats, 5-HT levels were increased in motor cortex (P<0.001) but decreased in cerebellum (P<0.001) when compared to control group of rats. The present study suggest that chronic administration of DPH induces alterations in monoamine levels in specific brain regions. DPH seems to mediate, its anticonvulsant action by selectively altering the monoamine levels in different brain regions.     

Mitochondrial monoamine oxidase activity and serotonin content of rat brain following gamma-irradiation

It is shown that gamma-irradiation of albino rats with a dose of 30 Gy leads to pronounced phase changes in monoaminoxidase activity and serotonin content in rat brain at early times after whole-body exposure. There is a similar direction of changes in the activity of the enzyme and in the content of the substrate adequate to the latter.     

Active-site-directed irreversible inhibition of rat brain 4-aminobutyrate aminotransferase by ethanolamine O-sulphate in vitro and in vivo

1. Partially purified preparations of rat brain 4-aminobutyrate aminotransferase were inhibited in a time-dependent manner by ethanolamine O-sulphate. The inhibition was not reversed by dialysis. 2. The inhibitor formed an initial reversible complex with the enzyme (K(i)=4.4x10(-4)m) and the rate of inactivation followed pseudo-first-order kinetics (k=7.15x10(-4)s(-1)). The inclusion of 4-aminobutyrate markedly slowed the rate of inactivation. 3. Ethanolamine O-sulphate did not inhibit glutamate decarboxylase, alanine aminotransferase or aspartate aminotransferase. 4. Intracisternal injection of ethanolamine O-sulphate into rats led to rapid inactivation of 4-aminobutyrate aminotransferase in vivo.     

Effect of cadmium and zinc on antioxidant enzyme activity in the gastropod, Achatina fulica

Heavy metal stress results in the production of O(2)(.-), H(2)O(2) and (.)OH, which affect various cellular processes, mostly the functioning of membrane systems. Cells are normally protected against free oxyradicals by the operation of intricate antioxidant systems. The aim of the present work is to examine the effect of CdCl(2) and ZnSO(4) on antioxidative enzyme activity in the gastropod, Achatina fulica. The concentrations of antioxidant enzymes--superoxide dismutase (SOD), catalase (Cat) and glutathione peroxidase (GPx)--and nonenzymatic antioxidants--glutathione and vitamin-C--were found to be decreased in both digestive gland and kidney of the gastropod, Achatina fulica treated with individual concentrations of 0.5 ppm and 1ppm of CdCl(2) and ZnSO(4), compared to that of control animals. Based on the above study, it is evident that Achatina fulica can be used as a bioindicator to monitor the environmental heavy metal pollution.     

Interrelationships among the ethanolamine phosphatides in myelinating rat brain

Abstract— —The ethanolamine phosphatide fraction was isolated from rat brain at 17, 19, and 22 days of age. Analysis by gas-liquid chromatography of the liberated fatty aldehydes and alkyl glyceryl ethers demonstrated a chain length composition quite distinct from that of the fatty acids in the comparable 1(3)-position of the diacyl phosphatides. [1-¹⁴C]-Acetate was administered intraperitoneally to 17-day-old rats. With the exception of the polyunsaturated fatty acids, isotope was readily incorporated into the individual side chains of the 1- and 2-positions of the glycerol moiety. Time studies revealed no readily discernible precursor-product relationships among the linkages in question. Therefore, although the long chain precursors for the alkenyl and alkyl ethers may be related by biosynthetic interconversion, the isotope data are suggestive of independent pathways of biosynthesis for the alkenyl ether, alkyl ether, and ester linkages.     

Effects of inhibitors on monoamine oxidase activity in perch (Perca flavescens) brain in vitro

1. Perch brain homogenates were incubated in vitro and monoamine oxidase (MAO) activity was determined fluorometrically, using a kynuramine substrate. 2. Clorgyline, harmaline and deprenyl inhibited MAO activity in a concentration-related manner, with single sigmoid inhibition curves, and the type A inhibitors harmaline and clorgyline were more effective than the type B inhibitor deprenyl. 3. Two types of inhibition were recognized in vitro; a fast-onsetting inhibition, similar to that produced by a reversible inhibitor, and a slow-onsetting inhibition, which is time- and concentration-dependent and presumably represents inactivation of the enzyme.     

Interactions of cadmium and zinc in cultured rat embryos

Rat embryos were cultured in serum taken from animals dosed with cadmium, or serum with cadmium added $\text{in}$$\text{vitro}$ in the presence or absence of additional zinc. Embryos explanted at day ten and grown in serum taken from animals sooner than 4 h after dosing had a reduced DNA content after 24 h culture. In one-hour serum, the yolk sac had become thick and brittle. Zinc ameliorated the effects but had no stimulatory effect on post eight-hour serum when serum zinc levels were at their lowest. The hypothesis that cadmium induces a maternal zinc deficiency sufficient to cause teratogenic changes could not be sustained. Embryos explanted at nine days were much more susceptible to cadmium added $\text{in}$$\text{vitro}$ than ten-day embryos. The principal anomaly, apart from a reduced DNA content, was a thickening of the yolk sac similar to that seen in embryos grown in serum taken from animals one hour after cadmium dosing. Addition of zinc to the medium prevented both of these effects. The suggestion is made that the cadmium-induced dysgenesis of the yolk sac precludes appropriate embryonic nutrition.