Brain Glutathione Levels Research Articles

Dorsal Anterior Cingulate Lactate and Glutathione Levels in Euthymic Bipolar I Disorder: 1H-MRS Study.

Objective:Oxidative stress and mitochondrial dysfunction are 2 closely integrated processes implicated in the physiopathology of bipolar disorder. Advanced proton magnetic resonance spectroscopy techniques enable the measurement of levels of lactate, the main marker of mitochondrial dysfunction, and glutathione, the predominant brain antioxidant. The objective of this study was to measure brain lactate and glutathione levels in bipolar disorder and healthy controls.Methods:Eighty-eight individuals (50 bipolar disorder and 38 healthy controls) underwent 3T proton magnetic resonance spectroscopy in the dorsal anterior cingulate cortex (2x2x4.5cm3) using a 2-D JPRESS sequence. Lactate and glutathione were quantified using the ProFit software program.Results:Bipolar disorder patients had higher dorsal anterior cingulate cortex lactate levels compared with controls. Glutathione levels did not differ between euthymic bipolar disorder and controls. There was a positive correlation between lactate and glutathione levels specific to bipolar disorder. No influence of medications on metabolites was observed.Conclusion:This is the most extensive magnetic resonance spectroscopy study of lactate and glutathione in bipolar disorder to date, and results indicated that euthymic bipolar disorder patients had higher levels of lactate, which might be an indication of altered mitochondrial function. Moreover, lactate levels correlated with glutathione levels, indicating a compensatory mechanism regardless of bipolar disorder diagnosis.

Selective Serotonin-norepinephrine Re-uptake Inhibition Limits Renovas-cular-hypertension Induced Cognitive Impairment, Endothelial Dysfunction, and Oxidative Stress Injury.

Hypertension has been reported to induce cognitive decline and dementia of vascular origin. Serotonin- norepinephrine reuptake transporters take part in the control of inflammation, cognitive functions, motivational acts and deterioration of neurons. This study was carried out to examine the effect of venlafaxine; a specific serotonin-norepinephrine reuptake inhibitor (SNRI), in two-kidney-one-clip-2K1C (renovascular hypertension) provoked vascular dementia (VaD) in albino rats. 2K1C technique was performed to provoke renovascular-hypertension in adult male albino Wistar rats. Learning and memory were assessed by using the elevated plus maze and Morris water maze. Mean arterial blood pressure- MABP, as well as endothelial function, were assessed by means of BIOPAC system. Serum nitrosative stress (nitrite/ nitrate), aortic superoxide anion, brain oxidative stress, inflammation, cholinergic dysfunction and brain damage (2,3,5-triphenylterazolium chloride staining) were also assessed. 2K1C has increased MABP, endothelial dysfunction as well as learning and memory impairments. 2K1C method has increased serum nitrosative stress (reduced nitrite/nitrate level), oxidative stress (increased brain thiobarbituric acid reactive species and aortic superoxide anion content along with decreased levels of brain superoxide dismutase, glutathione, and catalase), brain inflammation (increased myeloperoxidase), cholinergic dysfunction (increased acetylcholinesterase activity) and brain damage. Treatment with venlafaxine considerably attenuated renovascular-hypertension induced cognition impairment, endothelial dysfunction, serum nitrosative stress, brain and aortic oxidative stress, cholinergic function, inflammation as well as cerebral damage. The finding of this study indicates that specific modulation of the serotonin-norepinephrine transporter perhaps regarded as potential interventions for the management of renovascular hypertension provoked VaD.

Melatonin attenuated early brain injury induced by subarachnoid hemorrhage via regulating NLRP3 inflammasome and apoptosis signaling.

Subarachnoid hemorrhage (SAH) is a devastating condition with high morbidity and mortality rates due to the lack of effective therapy. Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation associated with the upregulation of apoptotic signaling pathway has been implicated in various inflammatory diseases including hemorrhagic insults. Melatonin is reported to possess substantial anti-inflammatory properties, which is beneficial for early brain injury (EBI) after SAH. However, the molecular mechanisms have not been clearly identified. This study was designed to investigate the protective effects of melatonin against EBI induced by SAH and to elucidate the potential mechanisms. The adult mice were subjected to SAH. Melatonin or vehicle was injected intraperitoneally 2 hr after SAH. Melatonin was neuroprotective, as shown by increased survival rate, as well as elevated neurological score, greater survival of neurons, preserved brain glutathione levels, and reduced brain edema, malondialdehyde concentrations, apoptotic ratio, and blood-brain barrier (BBB) disruption. Melatonin also attenuated the expressions of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cleaved caspase-1, interleukin-1β (IL-1β), and interleukin-6 (IL-6); these changes were also associated with an increase in the anti-apoptotic factor (Bcl2) and reduction in the pro-apoptotic factor (Bim). In summary, our results demonstrate that melatonin treatment attenuates the EBI following SAH by inhibiting NLRP3 inflammasome-associated apoptosis.

Effects of cell phone radiation on lipid peroxidation, glutathione and nitric oxide levels in mouse brain during epileptic seizure

The objective of the this study was to evaluate the effects of cellular phone radiation on oxidative stress parameters and oxide levels in mouse brain during pentylenetetrazole (PTZ) induced epileptic seizure. Eight weeks old mice were used in the study. Animals were distributed in the following groups: Group I: Control group treated with PTZ, Group II: 15min cellular phone radiation+PTZ treatment+30min cellular phone radiation, Group III: 30min cellular phone radiation+PTZ treatment+30min cellular phone radiation. The RF radiation was produced by a 900MHz cellular phone. Lipid peroxidation, which is the indicator of oxidative stress was quantified by measuring the formation of thiobarbituric acid reactive substances (TBARS). The glutathione (GSH) levels were determined by the Ellman method. Tissue total nitric oxide (NOx) levels were obtained using the Griess assay. Lipid peroxidation and NOx levels of brain tissue increased significantly in group II and III compared to group I. On the contrary, GSH levels were significantly lower in group II and III than group I. However, no statistically significant alterations in any of the endpoints were noted between group II and Group III. Overall, the experimental findings demonstrated that cellular phone radiation may increase the oxidative damage and NOx level during epileptic activity in mouse brain.

The neuroprotective and anti-apoptotic effects of melatonin on hemolytic hyperbilirubinemia-induced oxidative brain damage.

Melatonin exerts protection in several inflammatory and neurodegenerative disorders. To investigate the neuroprotective effects of melatonin in an experimental hemolysis-induced hyperbilirubinemia, newborn Sprague-Dawley rats (25-40 g, n = 72) were injected with phenylhydrazine hydrochloride (PHZ; 75 mg/kg) and the injections were repeated at the 24th hour. Rats were treated with saline or melatonin (10 mg/kg) 30 min before the first and second PHZ injections and 24 h after the 2nd PHZ injections. Control rats (n = 24) were injected with saline, but not PHZ. At sixth hours after the last injections of saline or melatonin, all rats were decapitated. Tumor necrosis factor (TNF)-α, IL-1β, IL-10 and brain-derived neurotrophic factor (BDNF) and S100B levels in the plasma were measured. Brain tissue malondialdehyde (MDA), glutathione (GSH) levels and myeloperoxidase (MPO) activities were measured, and brain tissues were evaluated for apoptosis by TUNEL method. In the saline-treated PHZ group, hemoglobin, hematocrit levels were reduced, and total/direct bilirubin levels were elevated when compared to control group. Increased plasma TNF-α, IL-1β levels, along with decreased BDNF, S100B and IL-10 values were observed in the saline-treated PHZ group, while these changes were all reversed in the melatonin-treated group. Increased MDA levels and MPO activities in the brain tissues of saline-treated hyperbilirubinemic rats, concomitant with depleted brain GSH stores, were also reversed in the melatonin-treated hyperbilirubinemic rats. Increased TUNEL(+) cells in the hippocampus of saline-treated PHZ group were reduced by melatonin treatment. Melatonin exerts neuroprotective and anti-apoptotic effects on the oxidative neuronal damage of the newborn rats with hemolysis and hyperbilirubinemia.

Carnosine and taurine treatments diminished brain oxidative stress and apoptosis in D-galactose aging model.

D-galactose (GAL) has been used as an animal model for brain aging and antiaging studies. GAL stimulates oxidative stress in several tissues including brain. Carnosine (CAR; β-alanil-L-histidine) and taurine (TAU; 2-aminoethanesulfonic acid) exhibit antioxidant properties. CAR and TAU have anti-aging and neuroprotective effects. We investigated the effect of CAR and TAU supplementations on oxidative stress and brain damage in GAL-treated rats. Rats received GAL (300 mg/kg; s.c.; 5 days per week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days per week) or TAU (2.5% w/w; in rat chow) for 2 months. Brain malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione transferase (GST) and acetylcholinesterase (AChE) activities were determined. Expressions of B cell lymphoma-2 (Bcl-2), Bax and caspase-3 were also evaluated in the brains by immunohistochemistry. GAL treatment increased brain MDA and PC levels and AChE activities. It decreased significantly brain GSH levels, SOD and GSH-Px but not GST activities. GAL treatment caused histopathological changes and increased apoptosis. CAR and TAU significantly reduced brain AChE activities, MDA and PC levels and elevated GSH levels in GAL-treated rats. CAR, but not TAU, significantly increased low activities of SOD and GSH-Px. Both CAR and TAU diminished apoptosis and ameliorated histopathological findings in the brain of GAL-treated rats. Our results indicate that CAR and TAU may be effective to prevent the development of oxidative stress, apoptosis and histopathological deterioration in the brain of GAL-treated rats.

Ciprofloxacin-induced neurotoxicity: evaluation of possible underlying mechanisms

Ciprofloxacin (CPX) is a fluoroquinolone antibiotic used for treating respiratory, urinary tract, gastrointestinal and abdominal infections. There are only a limited number of studies related to neurological adverse effects of this drug in therapeutic doses. Therefore, in the present study, we aimed to investigate the influence of CPX, when administered at pharmacological doses, on behavioral parameters of rats and the probable underlying mechanisms. CPX was administered in single oral daily doses of 20 and 50 mg/kg for 14 days in rats. CPX-induced depression and anxiety were evaluated by modified forced swimming test and elevated plus maze test, respectively. Also, spontaneous locomotor activity and motor coordination were assessed by activity cage and Rota-rod apparatus. Effects of CPX administration on brain serotonin, dopamine, γ-amino-butyric acid (GABA), glutamate, adrenaline and noradrenaline levels were determined by high performance liquid chromatography (HPLC) analysis. Contribution of oxidative stress to the changes induced by CPX administration was evaluated by measuring brain catalase, superoxide dismutase, glutathione (GSH) and malondialdehyde (MDA) levels. Our results indicated that depression-like and anxiety-like behaviors were observed only in the 50 mg/kg CPX-administered group with simultaneous decreases in the brain serotonin and GABA levels. In addition, in the brain homogenates of CPX-administered groups, increased MDA as well as decreased GSH and catalase activity with respect to their controls, indicated enhanced oxidative stress and weakened antioxidant defense system. In conclusion, repeated pharmacological doses of CPX were found to induce neurological toxicity. Also, altered brain neurotransmitter levels and increased oxidative stress observed in our study were thought to be the possible underlying mechanisms of ciprofloxacin-induced neurotoxicity.

Reconstituted mother tinctures of Gelsemium sempervirens L. improve memory and cognitive impairment in mice scopolamine-induced dementia model

Ethnopharmacological relevanceGelsemium sempervirens (L.) J.St.-Hil is a herb used for the treatment of various neuroses in both homeopathic and Ayurvedic systems. The present study examines whether Gelsemium reconstituted tincture can protect against scopolamine induced cognitive discrepancies in amnesic mouse model. In order to investigate the protective mechanism of Gelsemium against dementia, in vitro acetyl cholinesterase and β-secretase enzyme inhibition and estimation of glutathione level in mouse brain were carried out. Materials and methodsThe inhibition study on acetyl cholinesterase and β-secretase enzyme was conducted on brain homogenate supernatant spectrophotometrically using specific substrate. Cognitive enhancement activity was assessed by elevated plus maze and passive avoidance study in scopolamine induced dementia mouse model. Glutathione, an anti-oxidant, was measured spectrophotometrically from scopolamine induced amnesic mice brain supernatant using 5,5′-dithiobis 2-nitrobenzoic acid in the presence and absence of Gelsemium tincture. ResultsSignificant inhibition was found with Gelsemium on AChE and β-secretase enzyme with an IC50 of 9.25 and 16.25µg/ml, respectively, followed by increasing glutathione levels in comparison to the untreated dementia group. The effect of Gelsemium of scopolamine-induced cognitive deficits was determined by measuring the behavioral parameters and the antioxidant status of the brain after scopolamine (1mg/kg i.p.) injected amnesic mice. Gelsemium significantly demonstrated in vivo anti-dementia activity (60% protection) and increased exploratory behavior. ConclusionOur investigations indicated that alkaloid, iridoids and coumarin enriched reconstituted Gelsemium tincture extract displays promising cognitive enhancement in adult mice after short-term oral treatment. Hence, Gelsemium can be a promising anti-dementia agent, mediating the protection against amnesia, attention disorders and learning dysfunctions through dual inhibition of both acetyl cholinesterases (no false positive effect was shown), β-secretase and antioxidant activity.

Neuroprotective Effects of Citrus reticulata in Scopolamine-Induced Dementia Oxidative Stress in Rats

The purpose of the study was to evaluate the potential effects of Citrus reticulate (mandarin) peel methanolic extract (MPME) on memory dysfunction in rats. Memory impairment was produced by scopolamine (1.4 mg/kg, intraperitoneally injected). Brain acetylcholinesterase enzyme (AChE) activity was measured to assess the central cholinergic activity. This study also investigated the effect of scopolamine on norepinephrine, dopamine and serotonin content in rat hippocampus, striatum and cerebral cortex. In addition, the levels of brain lipid peroxidation (LPO), nitric oxide (NO) and glutathione (GSH) were estimated to assess the degree of oxidative stress. Scopolamine administration induced a significant impairment of central cholinergic activity in rats, as indicated by a marked increase in AChE activity. The impairment of the cholinergic system was associated with a significant alternation in brain monoamines. Scopolamine administration also caused oxidant damage (elevation in LPO and NO and reduction in GSH levels). Pretreatment of MPME (250 mg/kg, orally administered) significantly reduced scopolamine-induced alternation in brain monoamines with an attenuation of scopolamine-induced rise in brain AChE activity and brain oxidative stress. It is concluded that administration of mandarin peel extract, demonstrating antioxidant activity, may be of value for dementia exhibiting elevated brain oxidative status.

Citrus Peel Extract Attenuates Acute Cyanide Poisoning-Induced Seizures and Oxidative Stress in Rats

The primary aimed of this study was to investigate the potential protective effects of methanolic extract of citrus peel (MECP) on acute cyanide (KCN) poisoning-induced seizures and oxidative stress in rats. The intraperitoneal LD50 value of KCN (6.3 mg/Kg bwt), based on 24 hrs mortality, was significantly increased by 9, 52 or 113% by oral administration of MECP (500 mg/Kg bwt) pre-administered for 1, 2 and 3 days, respectively, in rats in a time-dependent manner. Intraperitoneal injection of the sublethal dose of KCN (3 mg/Kg bwt) into rats increased, 24 hrs later, lipid peroxidation (LPO), nitric oxide (NO), glutamate levels and acetylcholinesterase (AChE) activity in hippocampus, striatum and cerebral cortex. KCN also decreased brain glutathione (GSH) level and superoxide dismutase (SOD) and catalase (CAT) activities in these animals. Pre-treatment of rats with MECP inhibited KCN-induced increases in LPO, NO, and glutamate levels and AChE activity as well as decreases in brain GSH level and SOD and CAT activities. In addition, KCN significantly decreased norepinephrine, dopamine and serotonin levels in different brain regions which were resolved by MECP. From the present results, it can be concluded that the neuroprotective effects of MECP against KCN-induced seizures and oxidative stress may be due to the inhibition of oxidative stress overproduction and maintenance of antioxidant defense mechanisms.

Evaluation of Antiepileptic Activity of Methanolic Leaves Extract of <i>Tragia involucrata</i> Linn. in Mice

The present investigation was aimed to study an antiepileptic activity of methanolic extract of Tragia involucrata Linn in mice. In vivo screening models like maximal electroshock-induced convulsion (MES), pentylenetetrazole (PTZ) and picrotoxin (PTX) induced models are used to evaluate the antiepileptic effects of the extracts. The biochemical estimation was done by measuring the lipid peroxidation and reduced glutathione (GSH). In the MES induced convulsion, methanolic extract of Tragia involucrata (METI) at high dose (800 mg/kg body weight), showed high significant inhibition on tonic hind limb extension (THLE, 6.83 ±0.30***) and decrease in duration of stupor period (108.7 ±6.53***). In PTZ and PTX induced model METI (400 mg/kg and 800 mg/kg) showed significant delay on the onset of convulsions, decreased duration of convulsion and reduced mortality significantly. It also showed significant decrease in brain MDA level in lipid peroxidation profile, and increase in the brain glutathione levels in mice against PTZ induced convulsion. The results confirmed that Tragia involucrata Linn possesses dose dependent antiepileptic activity.

Evaluation of Antiepileptic Activity of Methanolic Leaves Extract of <i>Tragia involucrata</i> Linn. in Mice

The present investigation was aimed to study an antiepileptic activity of methanolic extract of Tragia involucrata Linn in mice. In vivo screening models like maximal electroshock-induced convulsion (MES), pentylenetetrazole (PTZ) and picrotoxin (PTX) induced models are used to evaluate the antiepileptic effects of the extracts. The biochemical estimation was done by measuring the lipid peroxidation and reduced glutathione (GSH). In the MES induced convulsion, methanolic extract of Tragia involucrata (METI) at high dose (800 mg/kg body weight), showed high significant inhibition on tonic hind limb extension (THLE, 6.83 ±0.30***) and decrease in duration of stupor period (108.7 ±6.53***). In PTZ and PTX induced model METI (400 mg/kg and 800 mg/kg) showed significant delay on the onset of convulsions, decreased duration of convulsion and reduced mortality significantly. It also showed significant decrease in brain MDA level in lipid peroxidation profile, and increase in the brain glutathione levels in mice against PTZ induced convulsion. The results confirmed that Tragia involucrata Linn possesses dose dependent antiepileptic activity.

Association between dairy intake and brain glutathione levels in older adults (1018.4)

Glutathione (GSH) plays a key role in protecting cells against oxidative stress. A reduction in GSH levels is noted in brain tissue undergoing oxidative stress in health and disease. We investigated the effect of dietary factors, specifically dairy intake, on oxidative stress, using a unique, noninvasive measure of brain GSH levels in older adults. Healthy subjects (n=57; 68 ± 6.1 yrs; BMI = 25 ± 4) whose daily dairy consumption was low (n=20; < 1 serving/day), moderate (n=22; >1,<3) or at recommended levels (15, >3) were recruited. Brain GSH was measured using a specially designed 1H MRSI technique for GSH at 3 T. Dietary intake was assessed with 7‐day food records, entered into NDS‐R. Total dairy servings were correlated with GSH levels in the frontal (Spearman Rs = .37, p = .004) and parietal regions (Rs = .46, p < .001). Correlations were also found between frontal GSH and milk (Rs = .36, p =.006) and between parietal GSH and milk (Rs = .38, p = .004), cheese (Rs = .40, p = .002) and calcium (Rs = .31, p = .022), but were lower than those for total dairy servings. The dairy intake groups did not differ in age, BMI, or fat consumption. Recommended dairy consumers had higher energy, carbohydrate, and protein intake, but these differences did not account for the relationship between dairy servings and GSH. The results suggest that increased dairy intake may be beneficial to brain health in aging via increasing cerebral antioxidant capacity.Grant Funding Source: Supported by Dairy Research Institute

Impact of caffeic acid on aluminium chloride-induced dementia in rats

Literature favours the in vitro neuroprotective role of caffeic acid, a naturally derived polyphenolic compound. This study was aimed to investigate the role of caffeic acid in experimental model of Alzheimer's disease. Firstly, caffeic acid was tested for in vitro anticholinesterase potential using rat brain homogenate. Later, in vivo antidementia activity of caffeic acid was assessed against aluminium chloride (AlCl3 )-induced dementia in rats. Behavioural (Morris water maze test) and brain biochemical parameters (acetylcholinesterase (AChE), catalase, glutathione-S-transferase (GST) activity, glutathione (GSH) and nitrite levels) were assessed to correlate the cognitive function with cholinergic transmission and oxidative stress. Rats administered with caffeic acid showed improved cognitive function in Morris water maze test. The antidementia activity of caffeic acid was confirmed by the reduction in brain AChE activity and nitrite levels. Further, caffeic acid corrected the diminished level of antioxidant enzymes such as catalase, GSH and GST in brain. These findings suggest the antidementia activity of caffeic acid against AlCl3 -induced dementia in rats. The outcome of present study offers a wider scope to screen caffeic acid against neurodegeneration associated disorders.

Lipid peroxidation and antioxidant responses in zebrafish brain induced by Aphanizomenon flos-aquae DC-1 aphantoxins

Aphanizomenon flos-aquae is a cyanobacterium that is frequently encountered in eutrophic waters worldwide. It is source of neurotoxins known as aphantoxins or paralytic shellfish poisons (PSPs), which present a major threat to the environment and human health. The molecular mechanism of PSP action is known, however the in vivo effects of this neurotoxin on oxidative stress, lipid peroxidation and the antioxidant defense responses in zebrafish brain remain to be understood. Aphantoxins purified from a natural isolate of A. flos-aquae DC-1 were analyzed using high performance liquid chromatography. The major components of the toxins were gonyautoxins 1 and 5 (GTX1 and GTX5, 34.04% and 21.28%, respectively) and neosaxitoxin (neoSTX, 12.77%). Zebrafish (Danio rerio) were injected intraperitoneally with 7.73μg/kg (low dose) and 11.13μg/kg (high dose) of A. flos-aquae DC-1 aphantoxins. Oxidative stress, lipid peroxidation and antioxidant defense responses in the zebrafish brain were investigated at various timepoints at 1–24h post-exposure. Aphantoxin exposure was associated with significantly increased (>1–2 times) reactive oxygen species (ROS) and malondialdehyde (MDA) in zebrafish brain compared with the controls at 1–12h postexposure, suggestive of oxidative stress and lipid peroxidation. In contrast, reduced glutathione (GSH) levels in the zebrafish brain exposed to high or low doses of aphantoxins decreased by 44.88% and 41.33%, respectively, after 1–12h compared with the controls, suggesting that GSH participated in detoxification to ROS and MDA. Further analysis showed a significant increase in the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) compared with the controls, suggesting elimination of oxidative stress by the antioxidant response in zebrafish brain. All these changes were dose and time dependent. These results suggested that aphantoxins or PSPs increased ROS and MDA and decreased GSH in zebrafish brain, and these changes induced oxidative stress. The increased activity of SOD, CAT and GPx demonstrated that these antioxidant enzymes could play important roles in eliminating excess ROS and MDA. These results also suggest that MDA, ROS, GSH and these three antioxidant enzymes in the brain of zebrafish may act as bioindicators for investigating A. flos-aquae DC-1 aphantoxins or PSPs and algal blooms in nature.

Effects of Dietary Soy Protein on Hematological and Tissue Oxidant/Anti- Oxidant Levels in Rats Exposed to Simulated Microgravity

Effects of a soy protein diet on oxidant and anti-oxidant levels in selected rodent tissues were investigated under simulated microgravity. Methods: Adult Male Rats were maintained either on a regular Purina Rat chow or on a 9.6% soy protein diet and allowed to remain in either non-suspended (control) or hind-limb-suspended (HLS) state via their tails at a 30 degree angle for 14 days. Body weights, food and water intakes were monitored daily during the entire study period. Hematological parameters, oxidant and. antioxidant levels in the brain, liver and pancreatic tissues were measured. Results: At term, the body weights of the hind limb suspended animals were found significantly decreased when compared with the non-suspended controls, p<0.05. There was no significant change in blood hematocrit and hemoglobin levels. After HLS, malondialdehyde (MDA) levels of brain tissues were marginally increased in the Purina chow group as compared to a significant increase in the soy suspended group (p<0.05). Similar observations were noted with liver and pancreatic tissues. In response to HLS, glutathione levels in brain and pancreatic tissues were increased in the Purina chow group (p<0.05) while in soy group, glutathione (GT) levels in both of these tissues were found relatively lower. Superoxide dismutase (SOD) levels were increased in all three tissues after HLS regardless of the dietary conditions. Conclusions: Data suggest that HLS induced a differential tissue specific oxidative response regardless of the dietary differences. Dietary soy protein lowered the oxidant levels under basal state but their effects were not sustained under HLS conditions significantly.

Ascorbic acid glucoside reduces neurotoxicity and glutathione depletion in mouse brain induced by nitrotriazole radiosensitazer

To investigate the potential of the anti-oxidant ascorbic acid glucoside (AA-2G) to modulate neurotoxicity induced by high doses of nitrotriazole radiosensitizer. Male and female C56Bl/6xCBA hybrid mice aged 8-14 weeks (weight 18-24 g) were used. Nitrotriazole drug radiosensitizer sanazole at a high dose of 2, 1 g/kg was per os administered to induce neurotoxicity at mice. Ascorbic acid glucoside was given 30 min before the sanazole administration. Serum ascorbic acid, brain glutathione level, as well as behavioral performance using open field apparatus were measured. Administration of high (non-therapeutic) doses of the nitrotriazole drug sanazole results in neurotoxicity in mice as evidenced from behavioral performance, emotional activity and depletion of the cellular antioxidant, glutathione, in the brain. The serum levels of ascorbic acid was also found reduced in high dose sanazole treated animals. Per os administration of ascorbic acid glucoside significantly reduced the neurotoxicity. This effect was associated with the prevention of glutathione depletion in mouse brain and restoring the ascorbic acid level in serum. Administration of ascorbic acid glucoside, but not ascorbic acid, before sanazole administration protected from sanazole-induced neurotoxicity by preventing the decrease in the brain reduced glutathione level and providing high level of ascorbic acid in plasma.

Chemoprotective potential of Coccinia indica against cyclophosphamide-induced toxicity.

Objective:Although cyclophosphamide (CP), an alkylating agent, is used in the treatment of cancer owing to its broad-spectrum efficacy, its metabolites exhibit severe undesired toxicities in normal cells. The present study was aimed to investigate the chemoprotective potential of Coccinia indica against CP-induced oxidative stress, genotoxicity, and hepatotoxicity.Materials and Methods:Rodents were orally pre-treated with Coccinia indica extract (200, 400, and 600 mg/kg) for five consecutive days. On 5th day, these animals were injected with CP (50 mg/kg i.p) and sacrificed after 24 hrs. for the evaluation of oxidative stress, hepatotoxicity, micronucleus formation, and chromosomal aberrations.Results:We found that the CP significantly increased malondialdehyde (MDA) and decreased catalase and glutathione (GSH) levels in brain, and it was significantly reversed by Coccinia indica extract (400 and 600 mg/kg). Further, pre-treatment with Coccinia indica extract (200, 400, 600 mg/kg) significantly and dose-dependently reduced micronuclei formation and incidence of aberrant cells. We also found that the CP-induced increase in the serum biomarker enzymes like alkaline phosphatase (ALP), alkaline aminotransferase (ALT), and aspartate aminotransferase (AST) were significantly reduced by Coccinia indica extract.Conclusion:Thus, the present results indicate the protective effect of Coccinia indica extract against CP-induced oxidative stress, genotoxicity, as well as hepatotoxicity.

Sub-lethal effects of titanium dioxide nanoparticles on the physiology and reproduction of zebrafish

There are limited data on the sub-lethal physiological effects of titanium dioxide nanoparticles (TiO2 NPs) in adult fishes, and the consequences of TiO2 NP exposure on reproductive success are also unclear. This study aimed to examine the sub-lethal effects of a 14-d aqueous TiO2 (TiO2 NP, 0.1 or 1.0mgl−1; TiO2 bulk, 1.0mgl−1) exposure on the physiology and reproductive health of zebrafish. After the 14-d exposure, fish were examined for haematology, whole body electrolyte and trace metal profiles, biochemistry, and histopathology. Then, during a 21-d post exposure recovery period, effects of the TiO2 exposure on reproductive success were evaluated. Whole body Ti concentrations increased significantly in fish exposed to both the 1.0mgl−1 TiO2 NP and bulk TiO2 compared to controls, but concentrations returned to control levels by the end of the recovery period. No change in erythrocyte counts were observed, but there was a two-fold decline in leukocyte counts in all TiO2 treatment groups relative to time-matched controls. Whole body electrolyte and trace metal profiles were not affected by exposure to TiO2, and there were no changes in Na+K+-ATPase activity in brain, gill or liver tissues. Total glutathione (GSH) levels in brain, gill and liver tissues were higher in fish exposed to TiO2 NP (both 0.1 and 1.0mgl−1) compared to bulk TiO2 and control fish. Histological examination of gill, liver, brain and gonad tissues showed little evidence of treatment-related morphological change. At the end of the 14-d exposure adult zebrafish were able to reproduce; however, the cumulative number of viable embryos produced was lower in fish exposed to 1.0mgl−1 TiO2 (both NP and bulk) by the end of the 21-d recovery period. Overall, this study showed limited toxicity of bulk or nano scale TiO2 during the exposure; however reproduction was affected in both bulk and NP 1.0mgl−1 groups.

The neuroprotection effect of pretreatment with olive leaf extract on brain lipidomics in rat stroke model

BackgroundRecent studies suggest that olive extracts suppress inflammation and reduce stress oxidative injury. We have attempted to determine the effect of dietary olive leaf extract (OLE) on brain lipidomics in rat stroke model. MethodsFive groups, each consisting of 12 male Wistar rats, were studied. First and second groups (control, and sham) received distilled water, while three treatment groups received oral olive leaf extract (OLE) for 30days (50, 75 and 100mg/kg/day, respectively). Two hours after the last dose, each main group was subdivided to Middle cerebral artery occlusion-operated and intact subgroup for assessment of neuropathology (neurologic deficit scores and infarct volume), brain lipid analysis and brain glutathione levels, respectively. ResultsOLE increased the brain cholesterol ester, cholesterol, cerebroside and phosphatidylcholine levels in doses of 50, 75 and 100mg/kg/day. OLE increased the brain triglyceride levels in doses of 75 and 100mg/kg/day and OLE reduced the brain ceramide levels in doses of 50, 75 and 100mg/kg/day in comparison to the control group (p<0.05). ConclusionAlthough further studies are needed, it seems that the mechanism of OLE-induced ischemic tolerance in rats is partly associated with changes in brain lipids level.