Activities Of Radical Scavenging Enzymes Research Articles

Investigation of Free Radical Scavenging Enzyme Activities and Lipid Peroxidation in Human Placental Tissues With Miscarriage

Miscarriage (early pregnancy failure) is a pregnancy-related disease, the pathophysiology of which is still not completely understood. Lipid peroxidation and alterations in antioxidant enzyme activities may be of importance in the pathogenesis of this disorder. This study was planned to investigate the possible relation between free radical scavenging enzyme activities and lipid peroxidation levels in placenta tissues with miscarriage. Placental tissue samples were obtained from 21 patients who had miscarried and 25 normal pregnant women undergoing elective abortion as a control group. Total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) enzyme activities and levels of thiobarbituric acid reactive substances (TBARS), antioxidant potential (AOP), and nonenzymatic superoxide radical scavenger activity (NSSA) were measured in the placental tissues. GSH-Px, CAT activities, and TBARS levels were found to be significantly increased, while T-SOD and NSSA values decreased in patients with early pregnancy failure when compared with women undergoing elective abortion (control group). However, there were no significant differences in AOP levels between the groups. Our results reflect oxidative stress in placenta tissues of early pregnancy failure, as the oxidative processes seem to be counteracted by the physiologic activation of antioxidant enzymes such as CAT and GSH-Px. Moreover, a compensatory mechanism might be developed against possible oxidative damage in patients with miscarriage.

Effect of supplemental l-ascorbyl-2-polyphosphate (APP) in enriched live food on the immune response of Penaeus vannamei exposed to ammonia-N

The effects of supplemental vitamin C, in the form l-ascorbyl-2-polyphosphate (APP) in enriched live food dietary ( Artemia) on reactive oxygen intermediates (ROIs) and free radical scavenging enzymes (such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione transferase) activities in muscle of Penaeus vannamei exposed to ambient ammonia-N were investigated. The results showed ROIs values of shrimps fed the starved and enriched Artemia increased with increased ammonia-N concentration. The ROIs value of shrimps fed the enriched Artemia exposed to increasing ammonia-N concentration were 37.4%, 26.4% and 31.1% lower ( P < 0.05) compared with those of shrimps fed the starved Artemia exposed to the same ammonia-N concentration. Total SOD, CAT, GPX, GST and GR activities of shrimps fed the enriched Artemia exposed to ammonia-N (2.568–3.852 mmol/l), were all higher ( P < 0.05) than that of shrimps fed the starved Artemia exposed to the same ammonia-N concentration. In addition, total SOD, CAT, GPX, GST and GR activities of shrimps of both dietary treatments decreased ( P < 0.05) with increased ammonia-N concentration. The results demonstrated that supplementation of ascorbic acid in enriched live food ( Artemia) enhanced the anti-oxidant capacity of shrimp, increasing its defense system that may fight against environmental stress leading to reduced ammonia toxicity.

The Anti-gastropathic and Anti-rheumatic Effect of Niga-ichigoside F1 and 23-Hydroxytormentic Acid Isolated from the Unripe Fruits of Rubus coreanus in a Rat Model

This study was undertaken to produce the clinical merits of two natural antinociceptive anti-inflammatory triterpenoids which synthetic anti-inflammatory drugs do not have. The triterpenoid glycoside niga-ichigoside F1 (NIF1) and its aglycone 23-hydroxytormentic acid (23-HTA), which were isolated from the unripe fruits of Rubus coreanus (Rosaceae), reduced rheumatoid arthritis (RA) factor and C-reactive protein (CRP) factor in Freund's complete adjuvant reagent-induced rats, suggesting that these two triterpenoids had an anti-rheumatic effect. It was also shown that treatment with NIF1 or 23-HTA reduced gastric lesion extent, acidity and total gastric acid output induced by EtOH plus sodium salicylate in a gastric secretion test. Moreover, 23-HTA had a greater effect than the glycoside, NIF1. To clarify the anti-gastropathic mechanism of these two compounds, their free radical scavenging activities in the gastric mucosa were examined in a rat EtOH-sodium salicylate-induced gastropathy model. The two compounds significantly increased superoxide dismutase and glutathione peroxidase activities, indicating that the healing effects of NIF1 and 23-HTA against gastropathy are associated with free radical scavenging enzyme activities. These results support the notion that the long-term administration of NIF1 or 23-HTA should overcome the adverse effects of synthetic anti-inflammatory drugs.

Reactive oxygen species scavenging activity during periodontal mucoperiosteal healing: An experimental study in dogs

Excessive release of reactive oxygen species (ROS) in wounded tissue due to inflammation and ischaemia is a deleterious and destructive phenomenon for the healing process. Hence, scavenging of ROS is one of the essential steps in normal wound repair. In this study, we presented a profile of free radical scavenging enzyme (FRSE) activity of periodontal mucoperiosteal wounds in order to investigate ROS activity during periodontal wound healing. Mucoperiosteal periodontal flaps were elevated in the mandibular buccal region of seven dogs between the first premolar and first molar teeth, creating acute incisional wounds in the inner side of the flaps and they were replaced 30 min after elevation. Gingival samples taken from certain biopsy regions at baseline (before flap elevation), day 3, 12, 21 and 30 were processed for detection of active amounts of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX). All enzyme activities had increased by more than 100% of their baseline levels by day 3. SOD activity decreased gradually from days 3 to 30 and reached a level lower than the baseline value. The increase in CAT activity continued until day 21, and decreased to a level higher than the baseline value by day 30. GPX also decreased from day 3, and reached a level less than its baseline value by day 30. Our results suggest that FRSEs may contribute to the detoxification of ROS during periodontal mucoperiosteal healing. This relationship may be utilized to facilitate soft tissue and/or flap management in periodontal or intra-oral treatments.

Familial Hypothalamic Digoxin Deficiency Syndrome

The case report of a family with coexistence of hypotension, recurrent respiratory infection, motor tics, obsessive-compulsive disorder (OCD), major depressive disorder, early onset osteoporosis, low body mass index, bulimia nervosa, and healthy aging with longevity is described. The family members had hyposexual behavior and less tendency toward spirituality. They did not have insomnia, but they did display tendency toward increased somnolence. No addictive behavior was observed. The family demonstrated a high level of bonding and affectionate behavior, and they were less creative, with an average intelligence quotient (IQ). There was a total absence of vascular thrombosis, systemic neoplasms and neuronal degeneration in the indexed family. All members of the indexed family were left hemispheric dominant. The levels of serum digoxin, HMG-CoA reductase activity, and dolichol were found to be decreased in the members of the indexed family, with a corresponding increase in red blood cell (RBC) Na+-K+ ATPase activity, serum ubiquinone and magnesium levels. There was increase in tyrosine catabolites and a reduction in tryptophan catabolites in the serum. The total and individual glycosaminoglycan fractions, carbohydrate residues of glycoproteins, activity of glycosaminoglycans (GAG) degrading enzymes, and glycohydrolases were decreased in the serum. The concentration of RBC membrane total GAG and carbohydrate residues of glycoproteins increased, while the cholesterol: phospholipid ratio of the membrane decreased. The activity of free radical scavenging enzymes were increased, while the concentration of free radicals decreased significantly. The same biochemical patterns were observed in left hemispheric dominance as opposed to right hemispheric dominance. The significance of these findings in the pathogenesis of these disorders is discussed.

Blood Levels of Trace Elements, Electrolytes, and Oxidative Stress/Antioxidant Systems in Epileptic Patients

Epileptic patients exhibited variably altered status of trace elements, electrolytes, and free radical scavenging enzyme activities. We investigated the effect of epilepsy and long-term antiepileptic drug therapy on the serum level of some trace elements (zinc, selenium, and copper), electrolytes (calcium, magnesium, sodium, and potassium), and antioxidants (glutathione peroxidase, and uric acid) and plasma levels of lipid peroxidation index (malondialdehyde), total antioxidant capacity, and ceruloplasmin. Seventy epileptic patients and fourteen controls were recruited in this study. In the treated group (particularly with valproate), we reported increases in the levels of zinc, calcium, sodium, malondialdehyde, and glutathione peroxidase and decreases in the levels of copper, total antioxidant capacity, and ceruloplasmin with no difference in selenium, magnesium, and potassium. However among untreated epileptics, uric acid level was increased and total antioxidant capacity was markedly lowered. We conclude that the above parameters balance differs in epileptics comparable to controls and hence their correlation to seizures pathophysiology and their degree of control or resistance to antiepileptic drug therapy. Better regulation of the lipid peroxidation and antioxidants and fewer disturbances in mineral metabolism were observed in monotherapy versus polytherapy and with carbamazepine versus valproate therapy.

Antioxidant potential of vitamins A, E and C in modulating oxidative stress in rat brain

Background: Stress is known to affect synaptic plasticity, dendritic morphology and induces neurotoxic damage in humans, probably through generation of free radicals. Both ex vivo antioxidant vitamins and in vivo free radical scavenging enzymes exist. In the present study, restraint stress induced pro-oxidant status of rat brain was evaluated in terms of measurement of glutathione (GSH), lipid peroxidation (thiobarbituric acid reactive substances, TBARS) and free radical scavenging enzymes activities. The efficacy of antioxidant vitamins A, E and C alone and in combination was also evaluated in modulating inherent antioxidant system in stressed rats. Methods: Rats were treated with vit A, E and C alone (15 mg/kg of body weight) and in combination vitamins (E and C) prior to and after 6 h of restraint stress exposure. Both nonstressed and stressed rats were handled simultaneously. Pro-oxidant status of brain tissue was evaluated by determining the levels of GSH, TBARS and activities of superoxide dismutase (SOD), glutathione- S-transferase (GST) and catalase (CAT). Results: Restraint stress induced a decrease in the level of GSH and the activities of SOD, GST and catalase, while the levels of TBARS were found elevated. Both pre-stress and post-stress vitamin treatments (either alone or combined) resulted in alteration of these parameters towards their controls values with a relative dominance by latter. Vitamin E was found most effective in restoring inherent antioxidant system, no additive effect was observed in combined vitamin treatment as expected. Conclusion: Immobilization of rats generated oxidative stress in rat brain, by decreasing the activities of SOD, GST, catalase and glutathione levels, while increasing the lipid peroxidation. Post stress vitamin E treatment was found most effective than vitamins A and C in enhancing the levels of glutathione and activities of SOD, GST and catalase and decreasing lipid peroxidation. Thus vitamin E can be given as a nutritional supplement for scavenging free radical generated in the brain tissues in order to reduce oxidative stress.

Implications of Reactive Oxygen Species in Heat Shock Induced Germination and Early Growth Impairment in Amaranthus lividus L.

An effort has been made to assess the role of reactive oxygen species in germination and subsequent growth of Amaranthus lividus under elevated temperature. Transfer of A. lividus seeds from 25 to 45 °C for 4, 8 and 12 h, during early imbibitional period reduced percentage of germination, relative germination performance, relative growth index and seedling length. Heat shock during early germination decreased also the activities of free radical scavenging enzymes like catalase, peroxidase and superoxide dismutase, increased the accumulation of superoxide, hydrogen peroxide and induced lipoxygenase mediated membrane lipid peroxidation. Membrane injury index and relative leakage ratio revealed a rise with concomitant reduction in membrane protein thiol content in heat shock raised seedlings. The results indicate that heat shock in A. lividus seeds induced an excessive generation of ROS and led to an oxidative membrane damage, causing early growth impairment.

The impact of cyanoglycoside rich fraction isolated from Cassava ( Manihot esculenta) on alcohol induced oxidative stress

The effects of feeding a cassava ( Manihot esculenta) rich diet on alcohol induced peroxidative damages were investigated in male albino rats. Rats were divided into four groups and maintained for 60 days as follows. (1) Control group: cassava free diet, (2) alcohol group: cassava free diet+ethanol (4 g/kg body wt/day), (3) cassava group: cassava diet and (4) alcohol+cassava group: cassava diet+ethanol (4 g/kg body wt/day). Results revealed that alcohol induced significant lipid peroxidation, since the lipid peroxidation products malondialdehyde (MDA), hydroperoxides and conjugated dienes were elevated in the liver. The activities of free radical scavenging enzymes such as superoxide dismutase (SOD), catalase and glutathione reductase were reduced and glutathione content was decreased in the liver. But the co-administration of a cassava rich diet increased the activity of free radical scavenging enzymes and glutathione content. The level of lipid peroxides in the liver was also decreased on co-administration of cassava. But the oxidative damage caused by cassava was potentiated by alcohol administration. These studies suggested that consumption of alcohol along with cassava offered some protection against the alcohol induced oxidative stress. So we isolated the cyanoglycoside rich fraction from cassava and its impact on rats administered alcohol was also investigated. The results revealed that alcohol induced oxidative stress was potentiated by the co-administration of cyanoglycoside rich fraction. These studies suggested that the fiber and antioxidant vitamins present in the cassava may be playing a protective role against the alcohol induced oxidative stress.

Modulation of Antioxidant Enzyme Expression and Function by Estrogen

Oxidative stress plays a pivotal role in the pathogenesis of atherosclerosis and can be effectively influenced by radical scavenging enzyme activity and expression. The vasoprotective effects of estrogens may be related to antioxidative properties. Therefore, effects of 17beta-estradiol on production of reactive oxygen species and radical scavenging enzymes were investigated. 17beta-estradiol diminished angiotensin II-induced free radical production in vascular smooth muscle cells (DCF fluorescence laser microscopy). 17beta-estradiol time- and concentration-dependently upregulated manganese (MnSOD) and extracellular superoxide dismutase (ecSOD) expression (Northern and Western blotting) and enzyme activity (photometric assay). Nuclear run-on assays demonstrated that 17beta-estradiol increases MnSOD and ecSOD transcription rate. Half-life of MnSOD mRNA was not influenced, whereas ecSOD mRNA was stabilized by estrogen. Copper-zinc SOD, glutathione-peroxidase, and catalase were not affected by estrogen. Estrogen deficiency in ovariectomized mice induced a downregulation of ecSOD and MnSOD expression, which was associated with increased production of vascular free radicals and prevented by estrogen replacement or treatment with PEG-SOD. In humans, increased estrogen levels led to enhanced ecSOD and MnSOD expression in circulating monocytes. Estrogen acts antioxidative at least to some extent via stimulation of MnSOD and ecSOD expression and activity, which may contribute to its vasoprotective effects.

Isoprenoid pathway related cascade in multiple myeloma.

This study assessed the changes in the isoprenoid pathway and its metabolites digoxin, dolichol and ubiquinone in multiple myeloma. The following parameters were assessed: isoprenoid pathway metabolites, tyrosine and tryptophan catabolites, glycoconjugate metabolism, RBC membrane composition and free radical metabolism. There was elevation in plasma HMG CoA reductase activity, serum digoxin and dolichol and a reduction in RBC membrane Na+ - K+ ATPase activity, and serum ubiquinone levels. Serum tryptophan, serotonin, nicotine, strychnine and quinolinic acid were elevated while tyrosine, dopamine, noradrenaline and morphine were decreased. The total serum glycosaminoglycans and glycosaminoglycan fractions, the activity of GAG degrading enzymes and glycohydrolases, carbohydrate residues of glycoproteins and serum glycolipids were elevated. The RBC membrane glycosaminoglycans, hexose and fucose residues of glycoproteins, cholesterol and phospholipids were reduced. The activity of all free radical scavenging enzymes, concentration of glutathione, iron binding capacity and ceruloplasmin decreased significantly while the concentration of lipid peroxidation products and NO increased. Hyperdigoxinemia related altered intracellular Ca++ mediated oncogene activation, dolichol induced altered glycoconjugate metabolism and ubiquinone deficiency related mitochondrial dysfunction can contribute to the pathogenesis of multiple myeloma. The biochemical findings reported could be the cause or the consequence of multiple myeloma.

Antioxidant action of flavonoids from Mangifera indica and Emblica officinalis in hypercholesterolemic rats

The oral administration of flavonoids from Mangifera indica and Emblica officinalis at a dose of 10 mg kg −1 body weight day −1 showed significant antioxidant action in cholesterol-fed experimental rats. The antioxidant activity of flavonoids was investigated on the basis of their effects on the activities of oxidative free radical scavenging enzymes, superoxide dismutase (SOD), catalase, glutathione peroxidase, and glutathione reductase, and reduced glutathione and lipid peroxide contents. The activities of free radical-scavenging enzymes were significantly elevated and lipid peroxide content was significantly decreased in flavonoid-treated hypercholesterolemic rats.

Accelerated aging-enhanced lipid peroxidation in bitter gourd seeds and effects of priming and hot water soaking treatments

Both priming (mixing seeds with moist vermiculite for 36 h at 20 °C) and hot water soaking (soaking seeds for 4 h in water at 40 °C) improved the percentage and mean emergence time (MET) of bitter gourd seeds at sub-optimal temperature of 20 °C. The amounts of MDA and total peroxide in imbibing primed and hot water-soaked seeds were reduced and the activities of several free radical and peroxide scavenging enzymes were increased in comparison with imbibing untreated seeds. Thus, the improved emergence performance might be partly contributable to decreased lipid peroxidation during imbibition and peroxide scavenging activities. The percentage of emergence was decreased and MET was increased by accelerated aging. Accelerated aging not only resulted in increased lipid peroxidation, but also in decreased activities of several free radical and peroxide scavenging enzymes. Both percentage and speed of emergence after accelerated aging were decreased to a greater extent in primed and particularly in hot water-soaked seeds than in control seeds. Moreover, lipid peroxidation was increased to a larger extent in pretreated than in untreated seeds after accelerated aging. Therefore, as in the case of pretreated seeds, the increased peroxide accumulation and the reduced enzyme activities appeared to be linked to the reduced emergence performance of aged seeds.

HYPOTHALAMIC DIGOXIN, HEMISPHERIC CHEMICAL DOMINANCE, AND ALZHEIMER'S DISEASE

This study assessed the changes in the isoprenoid pathway and the consequences of its dysfunction in Alzheimer's disease (AD). The isoprenoid pathway and digoxin status were also studied for comparison in individuals of differing hemispheric dominance to find the role of cerebral dominance in the genesis of Alzheimer's disease. There was elevation in plasma HMG CoA reductase activity, serum digoxin, and dolichol levels, and a reduction in serum magnesium, RBC membrane Na+-K+ ATPase activity, and serum ubiquinone levels. Serum tryptophan, serotonin, strychnine, nicotine, and quinolinic acid were elevated, while serum tyrosine, morphine, dopamine, and noradrenaline were decreased. The total serum glycosaminoglycans and glycosaminoglycan fractions, the activity of GAG degrading enzymes and glycohydrolases, carbohydrate residues of glycoproteins, and serum glycolipids were elevated in Alzheimer's disease. HDL cholesterol was reduced and free fatty acids increased. The RBC membrane glycosaminoglycans, hexose, and fucose residues of glycoproteins and cholesterol were reduced, while phospholipid increased. The activity of all free radical scavenging enzymes, concentration of glutathione, alpha tocopherol, iron binding capacity, and ceruloplasmin decreased significantly in Alzheimer's disease, while the concentration of lipid peroxidation products and NO increased. The hypomagnesemia-related NMDA excitotoxicity, ubiquinone deficiency related mitochondrial dysfunction, and altered glycoconjugates/lysosomal stability could contribute to the pathogenesis of Alzheimer's disease. The biochemical patterns, including hyperdigoxinemia observed in Alzheimer's disease, correlated with those obtained in right hemispheric chemical dominance. Right hemispheric chemical dominance is a predisposing factor for Alzheimer's disease.

Active Oxygen Scavenging Enzyme Activities and Glutathione, Ascorbic Acid and Lipid Peroxidation Levels in Developing Vitis Vinifera L. Leaves and Berries

ABSTRACTVariations and activities of active oxygen radical scavenging enzymes and the level of glutathione (GSH), lipid peroxide and ascorbic acid levels were measured during the developmental cycle and their relationship were examined in two grape cultivars, Kalecik Karasi and Sultani Çekirdeksiz (Vitis vinifera L.). The catalase activity was very low and did not change during growth, the activity of superoxide dismutase significantly decreased through the maturity. There was no significant difference between two cultivars for glutathione peroxidase activity at maturity. The maximum glutathione level was observed in berries of two Vitis vinifera L. cultivars. Ascorbic acid levels were significantly increased in young and old leaves. Changes in the activities of antioxidant enzymes and levels of glutathione, ascorbic acid and thiobarbituric acid reactive substances were related to the development of berries and leaves.

Effects of dietary vitamin E on antioxidant defence mechanisms of juvenile turbot (Scophthalmus maximusL.), halibut (Hippoglossus hippoglossusL.) and sea bream (Sparus aurataL.)

In order to enhance growth, survival and quality during early juvenile stages of marine fish it is important to avoid lipid oxidation problems that are known to cause pathologies and disease. The aim of the present study was to characterize and compare the antioxidant systems in juvenile marine fish of commercial importance in European aquaculture, namely turbot (Scophthalmus maximus), halibut (Hippoglossus hippoglossus) and gilthead sea bream (Sparus aurata). The experiment investigated the interaction of the dietary antioxidant micronutrient, vitamin E, with antioxidant defence systems. Fish were fed with diets of identical unsaturation index supplemented with graded amounts of vitamin E. The relationships between dietary and subsequent tissue vitamin E levels were determined as well as the effects of vitamin E supplementation on lipid and fatty acid compositions of both liver and whole fish, on the activities of the liver antioxidant defence enzymes, and on the levels of liver and whole body lipid peroxidation products, malondialdehyde (thiobarbituric acid reactive substances, TBARS) and isoprostanes. Growth and survival was only significantly affected in sea bream where feeding the diet with the lowest vitamin E resulted in decreased survival and growth. A gradation was observed in tissue vitamin E and polyunsaturated fatty acid (PUFA)/vitamin E levels in response to dietary vitamin E levels in all species. The activities of the main radical scavenging enzymes in the liver, catalase, superoxide dismutase and glutathione peroxidase generally reflected dietary and tissue vitamin E levels being highest in fish fed with the lowest level of vitamin E. The indicators of lipid peroxidation gave consistent results in all three species, generally being highest in fish fed with the unsupplemented diet and generally lowest in fish fed with the diet with highest vitamin E. In this respect, isoprostane levels generally paralleled TBARS levels supporting their value as indicators of oxidative stress in fish. Overall the relationships observed were logical in that decreased dietary vitamin E led to decreased levels of tissue vitamin E, and generally higher activities of the liver antioxidant enzymes and higher levels of lipid peroxides.

The changes of trace elements, malondialdehyde levels and superoxide dismutase activities in pregnancy with or without preeclampsia

Objectives: Increased free radical activity and lipid peroxidation may be implicated in the pathogenesis of preeclampsia. This study was initiated to assess antioxidant enzyme and trace metals’s status in preeclampsia. Design and methods: The comparision was made between the pregnant women with or without preeclampsia and healthy controls in this study. Samples were obtained from 24 normal nonpregnant (controls), 30 normal pregnant and 21 preeclamptic women in the third trimester. Lipid peroxidation end product, malondialdehyde (MDA), free radical scavenging enzyme activity, superoxide dismutase (SOD) and serum zinc (Zn), copper (Cu) levels were measured in either plasma/serum or erythrocytes of patients. Data were analyzed statistically using Student’s t-test. Results: In the preeclamptic group malondialdehyde, Cu levels were significantly increased, while Zn and SOD levels were significantly decreased compared to normal control group and healthy pregnant women. Conclusions: Our findings give support that radical scavenging SOD is consumed by the increased lipid peroxidation in preeclampsia. This data may indicate an involvement of free radicals in the pathophysiology of preeclampsia. This study suggests a relationship between increased MDA, Cu levels and decreased SOD, Zn levels in pregnancy and preeclampsia.

The protective role of L-carnitine against neurotoxicity evoked by drug of abuse, methamphetamine, could be related to mitochondrial dysfunction.

There is growing evidence that suggests that brain injury after amphetamine and methamphetamine (METH) administration is due to an increase in free radical formation and mitochondrial damage, which leads to a failure of cellular energy metabolism followed by a secondary excitotoxicity. Neuronal degeneration caused by drugs of abuse is also associated with decreased ATP synthesis. Defective mitochondrial oxidative phosphorylation and metabolic compromise also play an important role in atherogenesis, in the pathogenesis of Alzheimer's disease, Parkinson's disease, diabetes, and aging. The energy deficits in the central nervous system can lead to the generation of reactive oxygen and nitrogen species as indicated by increased activity of the free radical scavenging enzymes like catalase and superoxide dismutase. The METH-induced dopaminergic neurotoxicity may be mediated by the generation of peroxynitrite and can be protected by antioxidants selenium, melatonin, and selective nNOS inhibitor, 7-nitroindazole. L-Carnitine (LC) is well known to carry long-chain fatty acyl groups into mitochondria for beta-oxidation. It also plays a protective role in 3-nitropropioinc acid (3-NPA)-induced neurotoxicity as demonstrated in vitro and in vivo. LC has also been utilized in detoxification efforts in fatty acid-related metabolic disorders. In this study we have tested the hypothesis that enhancement of mitochondrial energy metabolism by LC could prevent the generation of peroxynitrite and free radicals produced by METH. Adult male C57BL/6N mice were divided into four groups. Group I served as control. Groups III and IV received LC (100 mg/kg, orally) for one week. Groups II and IV received 4 x 10 mg/kg METH i.p. at 2-h intervals after one week of LC administration. LC treatment continued for one more week to groups III and IV. One week after METH administration, mice were sacrificed by decapitation, and striatum was dissected to measure the formation of 3-nitrotyrosine (3-NT) by HPLC/Coularry system. METH treatment produced significant formation of 3-NT, a marker of peroxynitrite generation, in mice striatum. The pre- and post-treatment of mice with LC significantly attenuated the production of 3-NT in the striatum resulting from METH treatment. The protective effects by the compound LC in this study could be related to the prevention of the possible metabolic compromise by METH and the resulting energy deficits that lead to the generation of reactive oxygen and nitrogen species. These data further confirm our hypothesis that METH-induced neurotoxicity is mediated by the production of peroxynitrite, and LC may reduce the peroxynitrite levels and protect against the underlying mechanism of METH toxicity, which are models for several neurodegenerative disorders like Parkinson's disease.

Studies on the effect of monosodium glutamate (MSG) administration on the activity of xanthine oxidase, superoxide dismutase and catalase in hepatic tissue of adult male mice.

Subcutaneous administration of monosodium glutamate (MSG), to normal adult male mice, for six consecutive days at dose levels of 4 and 8 mg/g body weight, significantly increased the level of free radical initiating enzyme, xanthine oxidase, whereas the activity of free radical scavenging enzymes, like catalase and superoxide dismutase was significantly decreased in hepatic tissue. These observations suggested that ingestion of MSG at dose level of 4 mg/g body weight and above, induced oxidative stress in the hepatic tissue of adult male mice.

HYPOTHALAMIC DIGOXIN DEFICIENCY IN OBSESSIVE COMPULSIVE DISORDER AND LA TOURETTE S SYNDROME

The isoprenoid pathway related cascade was assessed in 15 patients with obsessive compulsive disorder (OCD) and la Tourette s syndrome (TS). The pathway was also assessed in right hemispheric dominant, left hemispheric dominant, and bihemispheric dominant individuals to assess whether hemispheric dominance has any correlation with these disease states. The levels of serum digoxin, HMG CoA reductase activity, and dolichol were found to be decreased in OCD and la Tourette s syndrome as well as in left hemispheric dominant individuals with a corresponding increase in RBC Na ´ +;-K ´ +; ATPase activity, serum ubiquinone, and magnesium levels. There was an increase in tyrosine and its catabo lites, and a reduction in tryptophan and its catabolites in the serum. The total and individual glycosaminoglycan (GAG) fractions, carbohydrate residues of glycoproteins, and the concentration of glycolipids decreased in the serum. The activity of GAG degrading enzymes and glycohydrolases were decreased. The RBC membrane glycoconjugates were increased while the membrane cholesterol:phospholipid ratio was decreased. The activity of free radical scavenging enzymes increased while the concentration of free radicals decreased significantly. On the other hand, there was hyperdigoxinemia and the reverse biochemical patterns in those with right hemispheric dominance. Membrane Na ´ +;-K ´ +; ATPase stimulation can result in decreased intracellular Ca ´ 2+; and increased magnesium levels. Increased levels of dopamine can lead to a tic syndrome, while reduced levels of serotonin and increased dopamine can both lead to obsessive compulsive disorder. Decrease in fucose and sialo-ligands, increased immunosuppressive morphine levels, decreased T-cell calcineurin signal transduction related to decreased intracellular calcium, reduced free radical production, and altered presentation of bacterial glycoconjugate antigens can lead to a hypoimmune response and recurrent respiratory infection in OCD patients. OCD and la Tourette s syndrome are associated with left hemispheric chemical dominance.