Biomedical subjects

P Arun

Publications and source records attributed to P Arun.

12 recordsLinked to original sources

PubMed2000

Tryptophan and tyrosine catabolic pattern in neuropsychiatric disorders.

Catabolism of tryptophan and tyrosine in relation to the isoprenoid pathway was studied in neurological and psychiatric disorders. The concentration of trytophan, quinolinic acid, kynurenic acid, serotonin and 5-hydroxyindoleacetic acid was found to be higher in the plasma of patients with all these disorders; while that of tyrosine, dopamine, epinephrine and norepinephrine was lower. There was increase in free fatty acids and decrease in albumin (factors modulating tryptophan transport) in the plasma of these patients. Concentration of digoxin, a modulator of amino acid transport, and the activity of HMG CoA reductase, which synthesizes digoxin, were higher in these patients; while RBC membrane Na+-K+ ATPase activity showed a decrease. Concentration of plasma ubiquinone (part of which is synthesised from tyrosine) and magnesium was also lower in these patients. No morphine could be detected in the plasma of these patients except in MS. On the other hand, strychnine and nicotine were detectable. These results indicate hypercatabolism of tryptophan and hypocatabolism of tyrosine in these disorders, which could be a consequence of the modulating effect of hypothalamic digoxin on amino acid transport.

Adult↗

PubMed2000

Endogenous strychnine, nicotine, and morphine--description of hypo and hyper-strychninergic, nicotinergic and morphinergic state in relation to neuropsychiatric diseases.

Previous work from this laboratory had demonstrated the presence of endogenous morphine, strychnine and nicotine in the mammalian brain and human serum samples. Morphine is synthesised from tyrosine and strychnine and nicotine from tryptophan. This study examines the role of strychnine, nicotine and morphine in neuropsychiatric disorders. The blood levels of tyrosine, tryptophan, strychnine, nicotine and morphine were studied as also RBC membrane Na(+)-K+ ATPase activity. It was found that serum tyrosine levels were reduced and tryptophan levels elevated in all neuropsychiatric disorders studied with a reduction in RBC Na(+)-K+ ATPase activity. Nicotine was present in significant amounts in serum of patients with schizophrenia, CNS glioma and syndrome X with multiple lacunar state. Morphine was present in significant amounts only in the serum of patients with multiple sclerosis and MDP. Strychnine was present in significant amounts in the serum of patients with epilepsy, Parkinson's disease and MDP. The presence of nicotine and strychnine in significant amounts could be related to elevated tryptophan levels suggesting the synthesis of these alkaloids from tryptophan. Morphine was not detected in most of the disorders owing to low tyrosine levels noted in them. Na(+)-K+ ATPase inhibition noticed in most of the disorders could be related to decreased hyperpolarising morphinergic transmission and increased depolarising nicotinergic and strychinergic transmission. The role of morphine, strychnine and nicotine in the pathogenesis of these disorders in the setting of membrane Na(+)-K+ ATPase inhibition is discussed.

Adult↗

PubMed2000

Isoprenoid pathway and free radical generation and damage in neuropsychiatric disorders.

Two substances which are products of the isoprenoid pathway, can participate in lipid peroxidation. One is digoxin, which by inhibiting membrane Na(+)-K+ ATPase, causes increase in intracellular Ca2+ and depletion of intracellular Mg2+, both effects contributing to increase in lipid peroxidation. Ubiquinone, another products of the pathway is a powerful membrane antioxidant and its deficiency can also result in defective electron transport and generation of reactive oxygen species. In view of this and also in the light of some preliminary reports on alteration in lipid peroxidation in neuropsychiatric disorders, a study was undertaken on the following aspects in some of these disorders (primary generalised epilepsy, schizophrenia, multiple sclerosis, Parkinson's disease and CNS glioma)--1) concentration of digoxin, ubiquinone, activity of HMG CoA reductase and RBC membrane Na(+)-K+ ATPase 2) activity of enzymes involved in free radical scavenging 3) parameters of lipid peroxidation and 4) antioxidant status. The result obtained indicates an increase in the concentration of digoxin and activity of HMG CoA reductase, decrease in ubiquinone levels and in the activity of membrane Na(+)-K+ ATPase. There is increased lipid peroxidation as evidenced from the increase in the concentration of MDA, conjugated dienes, hydroperoxides and NO with decreased antioxidant protection as indicated by decrease in ubiquinone, vit E and reduced glutathione in schizophrenia, Parkinson's disease and CNS glioma. The activity of enzymes involved in free radical scavenging like SOD, catalase, glutathione peroxidase and glutathione reductase is decreased in the above diseases. However, there is no evidence of any increase in lipid peroxidation in epilepsy or MS. The role of increased operation of the isoprenoid pathway as evidenced by alteration in the concentration of digoxin and ubiquinone in the generation of free radicals and protection against them in these disorders is discussed.

Central Nervous System Neoplasms↗

PubMed1999

Decreased hemolysis and lipid peroxidation in blood during storage in the presence of nicotinic acid.

BACKGROUND AND OBJECTIVES: There is increase in lipid peroxidation with consequent increase in hemolysis when blood is stored in di-(2-ethyl hexyl)phthalate (DEHP) plasticized bags. Studies carried out by us and others have indicated the ability of red cells to synthesize NAD+ from added nicotinic acid. Apart from the role of NAD+ in glycolysis, NADPH is required for reduction of oxidized glutathione to its reduced form by glutathione reductase. Reduced glutathione is an important antioxidant, which protects cell membrane from oxidative damage. Reduced glutathione is also involved in the regeneration of vitamin E, another important membrane antioxidant. In view of these, a study was undertaken to find out the effect of addition of nicotinic acid to the citrate-phosphate-dextrose-adenine (CPDA) solution on lipid peroxidation and integrity of red cells when whole blood is stored in DEHP plasticized bags. MATERIALS AND METHODS: Blood was collected in Penpol blood storage bags (which is a DEHP plasticized bag) in CPDA solution in the presence and absence of nicotinic acid. Various parameters of lipid peroxidation and membrane stability - level of malondialdehyde (MDA), conjugated dienes, vitamin E, reduced glutathione, plasma Hb and K+, levels of adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) were studied in the blood samples after various periods. RESULTS: Plasma Hb and K+ concentrations were significantly lower in the presence of added nicotinic acid both after 28 and 42 days. Concentration of MDA and conjugated dienes was lower and the levels of reduced glutathione and vitamin E higher in the presence of nicotinic acid. ATP levels were not significantly different, but 2,3-DPG levels were higher. pH of the blood was nearer to 7.0 in the presence of nicotinic acid, while leaching out of DEHP into the blood was significantly lower. CONCLUSION: Inclusion of nicotinic acid in the CPDA solution has a beneficial effect in that (1) it reduces plasma Hb and K+; (2) reduces lipid peroxidation and increases antioxidant protection; (3) maintains pH nearer to 7.0, and (4) decreases the leaching out of DEHP into the blood.

2,3-Diphosphoglycerate↗

PubMed1999

Changes in the composition of erythrocyte membrane during storage of blood in di-(2-ethyl hexyl) phthalate [DEHP] plasticized poly vinyl chloride (PVC) blood storage bags.

Very little information is available on the changes in the erythrocyte membrane composition during storage of blood at 4 degrees C, particularly with respect to the glycosaminoglycans and glycoproteins. In view of this, a detailed study was carried out on the changes in the membrane proteins, glycosaminoglycans (GAG), carbohydrate components of glycoproteins, cholesterol, phospholipids and vitamin E in blood stored in glass bottles and a di-(2-ethyl hexyl) phthalate (DEHP) plasticized PVC bag (Penpol blood bag). Blood was collected in CPDA solution in glass bottles and in Penpol blood bags and kept at 4 +/- 1 degrees C. Analysis was made immediately after blood collection and after 28 and 42 days. Significant increase in the total protein in the erythrocyte membrane was observed during storage of whole blood in glass bottles and Penpol blood bag at 4 degrees C. This increase was progressively more with increase in storage time. Significant changes were also observed in GAG, carbohydrate components of glycoproteins, cholesterol, phospholipids and vitamin E in the erythrocyte membrane under these conditions. The protein:GAG ratio, protein:carbohydrate ratio, cholesterol:phospholipid ratio as well as protein:lipid ratio showed significant increase in the membrane. The extent of these changes was lower in the Penpol bag, indicating the stabilizing effect of DEHP on the erythrocyte membrane.

Blood Preservation↗

PubMed1998

Increased lipid peroxidation of erythrocytes in blood stored in polyvinyl chloride blood storage bags plasticized with di-[2-ethyl hexyl] phthalate and effect of antioxidants.

BACKGROUND AND OBJECTIVES: Previous work in this laboratory has shown significant decrease in vitamin E in erythrocytes in blood stored in polyvinyl chloride (PVC) bags plasticized with di-[2-ethyl hexyl] phthalate (DEHP), and in erythrocytes incubated in vitro with DEHP. Since vitamin E is a major antioxidant, a study was carried out to find out whether this decrease observed in vitamin E has an effect on lipid peroxidation in blood stored in DEHP-plasticized PVC blood bags. MATERIALS AND METHODS: Blood was collected in Penpol blood storage bags (which is a DEHP-plasticized PVC bag) and parameters of lipid peroxidation, i.e. activity of superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione reductase, concentration of malondialdehyde (MDA), conjugated dienes, hydroperoxides, glutathione and vitamin E studied in erythrocytes after various periods of storage as compared to glass bottles. Erythrocytes were also incubated in vitro with DEHP with and without vitamin E, and changes in lipid peroxidation studied. RESULTS: Blood stored in Penpol bags showed increased lipid peroxidation in erythrocytes as compared to that stored in glass bottles, as is evident from a greater increase in MDA and a greater decrease in glutathione and a significant decrease in vitamin E. The addition of vitamin E decreased the formation of MDA and conjugated dienes and prevented the decrease in vitamin E. However in spite of increased lipid peroxidation in the presence of DEHP, the release of K+ and hemoglobin from erythrocytes was lower. When there was an increase in DEHP taken up by erythrocytes, there was a corresponding decrease in vitamin E. More important, whenever there was an increase in vitamin E in erythrocytes (when RBCs in the presence of DEHP were incubated with vitamin E), there was a progressive decrease in DEHP. CONCLUSION: DEHP caused increased lipid peroxidation in erythrocytes. At the same time, it decreased the release of K+ and hemoglobin from erythrocytes. It is possible that the stabilizing effect of DEHP on the erythrocyte membrane may offset the detrimental effects of the increased lipid peroxidation it causes.

Adult↗

PubMed1998

Identification and estimation of endogenous digoxin in biological fluids and tissues by TLC and HPLC.

A procedure for estimation of digoxin in biological samples after adding a known quantity of digoxin followed by extraction, separation by TLC and HPLC is described. The identity of digoxin thus extracted from rat brain has been established by reaction with digoxin antibody and by its inhibition of Na(+)-K+ ATPase activity. The method could be a better substitute to the routine radioimmunoassay as interfering substances are removed by TLC and HPLC.

Animals↗

PubMed1998

Endogenous alkaloids in the brain of rats loaded with tyrosine/tryptophan & in the serum of patients of neurodegenerative & psychiatric disorders.

Since binding sites for morphine, nicotine and strychnine exist in the brain, it is possible that they may have some role in neuronal function. The presence/variation in the levels of these alkaloids in the brain of rats fed tryptophan and tyrosine, and in the serum of patients with some neurodegenerative and psychiatric disorders were studied. Brain of rats loaded with tyrosine (500 mg/kg b wt X 14 days) showed increased amounts of morphine, while that from animals loaded with tryptophan (in the same dose) showed presence of strychnine and increased amounts of nicotine. Strychnine is being reported in mammalian brain for the first time. Serum of patients with epilepsy, Parkinson's disease (PD) and manic depressive psychosis (MDP) was also examined for the presence of these alkaloids. Serum of control subjects did not show the presence of any of these alkaloids, while that of all 3 patients groups contained strychnine. Morphine was present only in the serum of patients of MDP. Nicotine was present in trace amounts in the serum of all these patients. Presence of these alkaloids in the serum of patients of neurodegenerative and psychiatric disorders is being reported for the first time, to the best of our knowledge.

Alkaloids↗

PubMed1998

Effect of DEHP [di-(2-ethyl hexyl) phthalate] on lipid peroxidation in liver in rats and in primary cultures of rat hepatocytes.

The effect of DEHP [di-(2-ethly hexyl) phthalate] on lipid peroxidation in the liver in rats and in primary cultures of rat hepatocytes incubated with it was studied. The doses of DEHP used in this study corresponded to the low levels of this substance leaching into blood stored in DEHP plasticised PVC bags. Increased activity of superoxide dismutase (SOD) and catalase, increased concentration of malondialdehyde (MDA) and conjugated dienes and decrease in the concentration of glutathione and vitamin E have been observed in the liver of rats administered DEHP. Primary cultures of rat hepatocytes incubated with DEHP also showed increase in the activity of these enzymes, increase in the concentration of MDA and decrease in vitamin E. These results indicate that DEHP promotes lipid peroxidation. Incorporation of vitamin E along with DEHP into the culture medium containing hepatocytes counteracted these effects.

Animals↗

PubMed1998

Toxic effect of systemic administration of low doses of the plasticizer di-(2-ethyl hexyl) phthalate [DEHP] in rats.

DEHP [di-(2 ethyl hexyl) phthalate], a widely used plasticizer in blood storage bags, leaches out in appreciable amounts into blood (about 10 mg/100 ml) resulting in exposure of recipients of blood transfusion to this compound. Various reports indicate the toxicity of DEHP, particularly in liver and reproductive organs but all these studies used large doses (up to 2 g or more/Kg body weight) and oral route of administration which are not relevant to the intravenous administration during blood transfusion or the low amounts present in blood. We have studied changes in the activity of some important enzymes-gamma-GT, ALT, CPK, LDH, alkaline phosphatase, acid phosphatase, beta-glucuronidase and few other parameters like vitamin E, glutathione, serum albumin etc in rats administered low doses of DEHP (corresponding to transfusion of 2, 4, 6 and 10 units of blood). Histopathology of the organs has also been carried out. The results obtained indicate no serious toxic effects for DEHP at the level present in blood stored in DEHP plasticized blood bags as evidenced by the lack of any significant alteration in most of the biochemical parameters studied. Even in those cases where there was alteration (for e.g., decrease in the level of vitamin E) 24 hr after administration of DEHP, it returned to near normal level with in 72 hr to 7 days. No histopathological changes were observed in any of the organs at these levels of DEHP. It is concluded that DEHP did not cause any serious toxic effect even at doses corresponding to transfusion of several units of blood in a recipient.

Animals↗

PubMed1998

Decrease in the concentration of vitamin E in blood and tissues caused by di(2-ethylhexyl) phthalate, a commonly used plasticizer in blood storage bags and medical tubing.

BACKGROUND AND OBJECTIVES: Significant amounts of di(2-ethylhexyl) phthlate (DEHP) leach into blood stored in DEHP-plasticized PVC bags. The aim of this study was to find out whether DEHP at these low levels has any effect on the concentration of vitamin E, an antioxidant which affords protection against free radical damage. MATERIALS AND METHODS: DEHP was administered in low doses (150-750 microg/100 g body weight) to rats intraperitoneally and the concentration of vitamin E in the liver and testes was measured. Concentration of vitamin E was also measured in blood stored in glass bottles in the presence and absence of DEHP and in blood stored in DEHP-plasticized PVC bags. RESULTS: A decrease in the concentration of vitamin E was observed in all cases. Administration of vitamin E to rats and incorporation of vitamin E in the additive solution in the case of blood prevented this decrease. CONCLUSION: DEHP even at very low doses caused a decrease in the concentration of vitamin E in liver and tests of rats given this substance. Blood stored in DEHP-plasticized bags also showed a decrease in the concentration of vitamin E.

Animals↗

PubMed1998

Synthesis of NAD+ in erythrocytes incubated with nicotinic acid and the effect of di-(2-ethyl hexyl) phthalate (DEHP).

Synthesis of NAD+ from nicotinic acid by erythrocytes incubated in SAGM phosphate solution and effect of di-[2-ethyl hexyl] phthalate, a plasticizer commonly used in PVC blood/component storage bags, on this synthesis was studied. Erythrocytes are able to synthesise NAD+ in SAGM (sodium chloride, adenine, glucose, mannitol) phosphate solution and this synthesis was more in the presence of added nicotinic acid (optimum concentration 1 mM). The level of NAD+ decreased when the incubation period was increased from 24 to 48 hr. Glutamine had a deleterious effect on this synthesis, possibly due to the decrease in pH. Di-[2-ethyl hexyl] phthalate had an inhibitory effect on NAD+ synthesis when the cells were incubated in SAGM phosphate solution, either alone or in the presence of added nicotinic acid. There was significant decrease in the release of potassium and haemoglobin from the cells in the presence of nicotinic acid, indicating increased red cell stability.

Adenine↗