Brain Malondialdehyde Research Articles

The Effect of Metformin and Taurine, Alone and in Combination, on the Oxidative Stress Caused by Diabetes in the Rat Brain.

This study has compared the effects of metformin (MET) and taurine (TAU), singly and in combination, on the oxidative stress caused by diabetes in the rat brain. For this purpose, male Sprague-Dawley rats, 200-225 g in weight, assigned to groups of 6, were intraperitoneally (i.p.) treated with the diabetogen streptozotocin (STZ, 60 mg/kg, in citrate buffer pH 4.5) on day 1 and, after 14 days, orally (p.o.) with either MET, TAU or MET-TAU (each at 2.4 mM/kg, in water). Control rats received only citrate buffer pH 4.5 (2 mL) or only STZ on day 1 by the i.p. route. All the animals were sacrificed by decapitation on day 57 and their brains collected by the freeze clamp technique. Blood samples were placed in heparinized tubes and used for the assay of the plasma glucose (GLC) and blood insulin (INS) levels. Immediately thereafter, the brains were surgically removed and a portion was used to prepare a homogenate in 0.1 M PBS pH 7.4, which was used for the assay of indices of oxidative stress. Diabetes raised the plasma GLC level (+313%) but lowered that of the blood INS (-76%) compared to corresponding values from nondiabetic rats. In addition it raised the brain malondialdehyde level (+59%) but lowered the reduced/disulfide glutathione ratio (-46%), and activities of catalase (-43%), glutathione peroxidase (-48%), superoxide dismutase (-65%), glutathione reductase (-50%) and glutathione S-transferase (-51%) significantly (all at p < 0.001). Except for the greater decrease in GLC (+90% vs. +22%) and increase in INS (-26% vs. -52%) levels seen in rats receiving MET than in rats receiving TAU, these compounds protected the brain against oxidative stress to significant (p ≤ 0.05%) and rather similar extents. Furthermore, the concurrent administration of MET and TAU to the diabetic rats led to brain values of indices of oxidative stress that were lower than those attained with MET alone, although generally not to a statistically significant degree.

Evaluation of Nootropic Potential of Green Peas in Mice

Green Peas are tiny powerhouse of nourishment. They are rich in alpha-linolenic acid, flavonoids, carotenoids, phenolic acids, polphenols and pisumsaponins. The present study was employed to assess nootropic potential of Green Peas (Pisum sativum). Elevated Plus Maze model and Passive avoidance Paradigm served as Exteroceptive Behavioral models. Scopolamine and ethanol were used as amnesic agents. Pisum sativum (PS) in two different concentrations (2.5% w/w and 5% w/w) were administered with diet, for 15 successive days to mice. A decrease in transfer latency and increase in step down latency was observed. Further, green peas ameliorated memory deficits induced by scopolamine and ethanol in mice. PS produced significant increase in brain Glutathione levels, declined brain Malondialdehyde levels and reduced brain Acetylcholinesterase activity. Therefore, behavioral effects of PS would be worthwhile in management of cognitive dysfunctions.

Neuroprotective Effect of Erythropoietin on Phenylhydrazine-Induced Hemolytic Hyperbilirubinemia in Neonatal Rats.

Neonatal unconjugated hyperbilirubinemia might cause severe bilirubin neurotoxicity in especially hemolytic conditions. The study aimed to elucidate the potential neuroprotective effects of erythropoietin (EPO) in hemolysis-induced hyperbilirubinemia. In newborn rats, hyperbilirubinemia secondary to hemolysis was induced by injecting with phenylhydrazine hydrochloride (PHZ) and rats were injected with either vehicle or EPO. At 54th hour of the PHZ injection, rats were decapitated. Serum levels of TNF-α, IL-1β, IL-10, brain-derived neurotrophic factor (BDNF) and S100-B and brain malondialdehyde, glutathione levels and myeloperoxidase activities were measured. TUNEL staining and NF-κB expression were evaluated. As compared to control pups, in vehicle-treated PHZ group, TNF-α and IL-1β levels, malondialdehyde level and myeloperoxidase activity were increased with concomitant decreases in IL-10 and glutathione. All EPO regimens reversed PHZ-induced alterations in IL-10, TNF-α, malondialdehyde and glutathione levels. Three-day-treatment abolished increases in myeloperoxidase activity and IL-1β levels, while BDNF and S100-B were elevated. Increased TUNEL (+) cells and NF-κB expressions in the brain of PHZ group were reduced in the 3-day-treated group. EPO exerted anti-inflammatory effects on PHZ-induced neural damage in newborn rats, while the neuroprotection was more obvious when the treatments were repeated successively. The results suggest that EPO treatment may have a therapeutic potential in supporting neuroplasticity in the hyperbilirubinemic neonates.

Impaired Cognitive Performance and Metabolic Disturbance in Streptozotocin-Nicotinamide Induced Type 2 Diabetes Mellitus and the Protective Effect of Nigerian Propolis

Defects in insulin signaling and oxidative stress are implicated in cognitive dysfunction in diabetes. This study evaluated the effects of propolis on cognitive impairment in streptozotocin-nicotinamide model of type 2 diabetes mellitus in Wistar rats. Diabetes was induced by single intraperitonieal administration of streptozotocin (65 mg/kg) 15 min after nicotinamide (110 mg/kg) had been adminstered. Diabetic animals were treated with glibenclamide (5 mg/kg), propolis (200 and 300 mg/kg), or normal saline for 4 weeks after which spatial memory was assessed with the Morris’ water maze (MWM). At the end of the study the animals were euthanized and blood collected via cardiac puncture while the brain was homogenized. Insulin was assayed from plasma while malondialdehyde (MDA), superoxide dismutase (SOD), gluthatione (GSH) and catalase were assayed from brain homogenate. Homeostatic model assessment (HOMA) was used as marker for insulin resistance. Significant rise in blood glucose, plasma insulin, and brain MDA (P &lt; 0.05) with reduction in SOD, GSH, and catalase levels were observed in the diabetic group. Treatment with 200 and 300 mg/kg propolis and glibenclamide significantly decreased blood glucose, plasma insulin, and MDA (P &lt; 0.05) and increased brain levels of SOD, GSH and catalase. Propolis (200 and 300 mg/kg) also significantly (P &lt; 0.05) decreased escape latency in the MWM in comparison to the diabetic group. Nigerian propolis thus seems to protect against impaired cognitive performance in experimental diabetes mellitus.

Effect of dietary supplementation of Padauk (Pterocarpus soyauxii) leaf on high fat diet/streptozotocin induced diabetes in rats' brain and platelets.

This study investigated the effects of Padauk leaf on brain malondialdehyde (MDA) content, acetylcholinesterase (AChE) activities, ectonucleotidases and adenosine deaminase (ADA) activities in the platelet of high fat diet and streptozotocin (STZ)-induced diabetic rats. The animals were divided into six groups (n=7): normal control rats; diabetic rats+high fat diet (HFD); diabetic rats+HFD+Metformin; diabetic rats+HFD+acarbose; diabetic rats+HFD+10% Padauk leaf; normal rats+basal diet+10% Padauk leaf. After 30days of experiment comprising of acclimatization, dietary manipulation, pre-treatment with STZ and supplementation with Padauk leaf, the animals were sacrificed and the rats' brain and blood were collected for subsequent analysis. The results demonstrated that the elevated MDA content and AChE activity in the diabetic rats were significantly reduced when compared with the control rats. Furthermore, the increased NTPDases, 5'-nucleotidase and ADA activities in the diabetic rats were significantly reduced when compared with the control rats. This study demonstrated that Padauk leaf exhibited modulatory effects on purinergic and cholinergic enzymes involved in the prevention of platelet abnormality and consequent vascular complications in diabetic state.

Anticonvulsant activity of the antidepressant drug, tianeptine, against pentylenetetrazole-induced seizures mitigates cognitive impairment in rats.

Treatment of depression, a common comorbidity in patients with epilepsy, is restricted as certain antidepressants are considered to be proconvulsants. In contrast, anticonvulsant effects have been reported with some antidepressants. In the present study, the effect of tianeptine, an antidepressant, was evaluated against pentylenetetrazole (PTZ)-induced seizures, cognitive impairment and oxidative stress in rats. Tianeptine was administered in three doses (20, 40 and 80 mg/kg) 30 min before PTZ (60 mg/kg, intraperitoneally). MK801, an N-methyl-D-aspartate antagonist, and naloxone, an opioid receptor antagonist, were administered with tianeptine to evaluate the involvement of N-methyl-D-aspartate and opioid receptors, respectively. Morris water maze, elevated plus maze and passive avoidance tests were performed for behavioural assessment. Brain malondialdehyde and reduced glutathione levels were estimated as markers of oxidative stress. Tianeptine showed dose-dependent protection against PTZ seizures. Coadministration of tianeptine with MK801 potentiated the anticonvulsant effect of tianeptine. The protective effect of tianeptine against PTZ seizures was mitigated when tianeptine was administered with naloxone. Impairment of learning and memory by PTZ was prevented by tianeptine. Tianeptine also attenuated the seizure-induced increased oxidative stress. Thus, tianeptine showed an anticonvulsant effect along with amelioration of seizure-induced cognitive impairment and oxidative stress. Hence, tianeptine could be a useful drug in epileptic patients with depression, with the advantage of having both antidepressant and antiepileptic effects.

Synergistic Antiparkinsonian Effect of Flunarizine, Glibenclamide and B Vitamins in a Rat 6-Hydroxydopamine Model; The Role of Malondialdehyde

Background: The current study evaluated the effects of a combination of flunarizine (flu) a calcium channel blocker, glibenclamide (Glib), a KATP channels blocker and B vitamins (B com) on the behavioral symptoms of 6-hydroxydopamine (6-OHDA)-induced model of Parkinson disease to evaluate the synergistic antiparkinsonian effects of the drugs and supplements. Also the level of malondialdehyde (MDA) was measured in blood and brain suspensions to find probable neuroprotective mechanism of these materials. Methods: 6-OHDA was injected into striatum of rats by stereotaxic surgery. Pretreatment with flu, Glib and B com was started before the surgery and continued to three weeks after the surgery. Development and severity of Parkinson disease were evaluated by the conventional behavioral tests. MDA values were measured spectrophotometrically, using thiobarbituric acid test and the MDA standard curve. Results: Pretreatment with a combination of flu, Glib and B com ameliorated the behavioral symptoms of Parkinson disease. The effect of the combination was significantly more potent than those of flu, Glib or B com, solely. Pretreatment with the combination or using only Glib or B com separately, reduced the level of MDA in blood and brain, significantly. However, the effect of the combination was significantly more potent than those of Glib or B com, solely. Conclusions: Since the severity of the behavioral symptoms in the 6-OHDA-induced model of Parkinson disease reflects the degree of the lesion in substantia nigra (SN) dopaminergic neurons, it is suggested that using the combination had neuroprotective effects. The obtained data suggest a synergistic neuroprotective and antiparkinsonian effect for flu, Glib and B com. At least, a part of this effect was mediated through inhibition of oxidative stress. Keywords: 6-Hydroxydopamine, Flunarizine, Glibenclamide: B Vitamins, Behavioral Symptoms, Malondialdehyde

Ferulic acid exhibits antiepileptogenic effect and prevents oxidative stress and cognitive impairment in the kindling model of epilepsy

AimsSome conventional antiepileptic drugs induce oxidative stress and cognitive impairment which may limit their clinical applications. Ferulic acid is a phenolic phytochemical with antioxidant and neuroprotective properties that prompted us to evaluate its therapeutic potential in epilepsy which is usually associated with oxidative stress and cognitive decline. Materials and methodsMale Wistar rats received 30mg/kg of pentylenetetrazole (PTZ) intraperitoneally (i.p.) once every alternate day until the development of kindling. The locomotor activity, elevated plus maze, and passive avoidance tests were performed. Oxidative stress was evaluated by the determination of brain malondialdehyde and reduced glutathione. The effects of pre-treatment with ferulic acid (25, 50, 75, and 100mg/kg, i.p.) against PTZ-kindled seizures, cognitive impairment, and oxidative stress were investigated. Key findingsKindling was developed 34.18±1.54days after PTZ treatment which was associated with generalized tonic-clonic seizures (GTCS), myoclonic jerks, cognitive deficit, and oxidative stress. Ferulic acid at doses of 75 and 100mg/kg significantly reduced the seizure score, number of myoclonic jerks, cognitive decline and oxidative stress. Spontaneous locomotor activity did not significantly differ between the groups. SignificanceFerulic acid exhibits antiepileptogenic effect and prevents oxidative stress and cognitive impairment induced by PTZ kindling. Therefore, this phenolic phytochemical appears as a promising adjuvant for antiepileptic drugs. Meanwhile, further experimental and clinical studies are required to provide insights into the cellular/molecular mechanism(s) underlying the action of ferulic acid.

Neuroprotective effect of Cucumis melo Var. flexuosus leaf extract on the brains of rats with streptozotocin-induced diabetes

The central nervous system is one of the most vulnerable organs affected by the oxidative stress associated with diabetes mellitus. Healthy food provides an important source for antioxidants. Therefore, the protective effect of Cucumis melo var. flexuosus (C. melo var. flexuosus) leaf extract on the brains of diabetic rats was investigated. Adult male albino rats divided into 5 groups of 6 rats each were assigned into a normal control group and four diabetic groups. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (STZ; 60mg/kg bw). One of the four diabetic groups was left untreated and was considered as a diabetic control group while the three other groups were treated with C. melo var. flexuosus leaf extract at the doses of 30, 60 and 120mg/kg bw for a period of 30days. After completion of experimental duration plasma and brains were used for evaluating biochemical changes. The obtained data showed that C. melo var. flexuosus leaf extract treatment lowered blood glucose, glycated hemoglobin, brain tumor necrosis factor-alpha, interleukin levels, brain malondialdehyde content and caspase-3 activity. Furthermore, the treatment resulted in a marked increase in plasma dopamine, melatonin, brain vascular endothelial growth factor-A levels, brain catalase and superoxide dismutase activities. From the present study, it can be concluded that the C. melo var. flexuosus leaf extract exerts a neuroprotective effect against oxidative damage associated with diabetes.

Novel effect of Daflon and low-dose γ-radiation in modulation of thioacetamide-induced hepatic encephalopathy in male albino rats.

This study was designed to evaluate the hepato and neuroprotective activity of Daflon and low-dose γ radiation on thioacetamide (TAA)-induced liver damage and hepatic encephalopathy (HE) in rats. Effect of daily Daflon treatment (100 mg/kg body weight, Per OS (p.o.) for consecutive 3 days) and/or fractionated low-dose γ-radiation (LDR; 0.25 Gy, twice the total dose of 0.5 Gy at the 1st and 3rd day, respectively) was evaluated against TAA (300 mg/kg, intraperitoneal × 3) induced liver damage and HE in rats. Serum aspartate transaminase, alanine transaminase, γ-glutamyltransferase, total bilirubin, ammonia, and manganese were estimated to evaluate liver function. In addition, malondialdehyde (MDA) as well as reduced glutathione (GSH), glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT) were determined to assess antioxidant capacity in liver tissue. Moreover, hepatic apoptotic markers (cysteine-dependent aspartate-directed proteases 3, 8 (caspase-3, 8) and cytochrome C) were estimated to indicate hepatic apoptosis. HE was evaluated through the determination of whole brain ammonia, manganese, MDA, GSH, GPX, SOD, CAT, and caspase-3. The cognitive and locomotor deficits were assessed via step through passive avoidance test, activity cage (actophotometer), γ-aminobutyric acid, and N-methyl-d-aspartate/adenosine triphosphate-neuronal nitric oxide synthase/nitric oxide-cyclic guanosine monophosphate axis in rats' cerebella and hippocampi. The involvement of hypoxia inducible factor-1α, aquaporine-4, and matrix metalloproteinase 9 in association with the brain water content (%) in the whole brain as an index for brain edema was also evaluated. The obtained results showed a marked amelioration of the aforementioned biochemical parameters and behavioral tasks which is supported by histopathological and immunohistochemical examination. It could be concluded that Daflon and LDR afforded hepatoprotection and neuroprotection against TAA-induced acute liver damage and HE.

Antioxidant and anti-aging activities of polysaccharides from Calocybe indica var. APK2

The crude polysaccharides were extracted from the fruiting bodies of Calocybe indica (CIP). The antioxidant activities of CIP were evaluated both in vitro and in vivo. Chemical characteristics of the polysaccharides were investigated. In in vitro antioxidant assay, CIP showed noticeable 2,2-diphenyl-1-picryl-hydrazyl (DPPH), hydroxyl radical scavenging activities, reducing power and lipid peroxidation inhibition. Chemical analysis showed the presence of carbohydrate, protein and the FTIR spectra revealed the presence of general characteristic absorption peak of the polysaccharides. For in vivo antioxidant activity, two different doses of CIP were orally administrated over a period of 6 weeks in a d-galactose (d-gal) induced aged mice model. Significantly lowered activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), levels of glutathione (GSH) and elevated malondialdehyde (MDA) levels were observed in brain and serum of d-galactose induced rats, when compared to control rats. Administration of CIP significantly raised the activities of SOD, CAT, GPx, levels of GSH and lowered the levels of MDA in mice brain and serum in a dose-dependent manner. The results suggested that CIP had potent antioxidant activity and could minimize the occurrence of age-associated disorders associated with involvement of free radicals.

Oleuropein ameliorates arsenic induced oxidative stress in mice

The objective of this study is to investigate the potential preventive effect of oleuropein in an experimental arsenic toxicity in mice. For this purpose, mice were exposed to 5mg/kg/day sodium arsenite (NaAsO2) in drinking water and treated with 30mg/kg/day oleuropein for 15 days. At the end of the experiment, animals were sacrificed and selected organs were processed for biochemical and histopahtological investigations. Blood, liver, kidney and brain malondialdehyde (MDA) and nitric oxide (NO) levels were determined by colorimetric methods. Protein carbonyl content is measured by a commercial kit. Liver morphology and immunoreactivity for inducible NOS (iNOS) and endothelial NOS (eNOS) was evaluated microscopically. Level of NO was determined to decrease in blood and tissues whereas MDA increased in arsenic given mice. Tissue protein carbonyl content also increased in this group. Immunoreactivity for iNOS and eNOS was noted to increase with arsenic treatment. Oleuropein treatment had significant effects in normalizing the MDA and NO levels as well as protein carbonyl content. Immunohistochemical staining also showed reduction of the expression of iNOS and eNOS in liver. The results indicate that oleuropein ameliorates oxidative tissue damage by scavenging free radicals.

Relationship of antioxidant and oxidative stress markers in different organs following copper toxicity in a rat model

Copper (Cu) at a higher level becomes toxic and it can catalyze the formation of highly reactive hydroxyl radical. We report the vulnerability of liver, kidney and brain to different dose of copper sulfate (CuSO4) induced oxidative stress at different time duration. Fifty-four male Wistar rats (weight range=205±10g) were equally divided into three groups. CuSO4 was administered orally to the experimental groups (Group-II and III) up to 90days in a dose of 100 and 200mg/Kg body weight per day. Saline water was given to the control group (Group-I). At the end of 30, 60 and 90days of administration, neurobehavioral studies were done and six rats from each group were sacrificed. Their liver, kidney and brain tissues were subjected for Cu, glutathione (GSH), malondialdehyde (MDA) and total antioxidant capacity (TAC) assay. Blood urea nitrogen (BUN), serum creatinine, bilirubin and transaminases were measured. GSH, TAC and MDA levels were correlated with the markers of respective organ dysfunction.Administration of CuSO4 resulted in increased free Cu and MDA level, and decrease GSH and TAC levels in group-II and III compared with group-I. In experimental groups, the reduction in TAC and GSH levels was maximum in liver tissue followed by brain and kidney; whereas increase in MDA level was highest in liver followed by brain and kidney at 30, 60 and 90days. TAC and GSH levels in the liver inversely correlated with serum transaminases and bilirubin, and tissue free Cu, and positively correlated with MDA levels. Free Cu level in kidney tissue and BUN inversely correlated with TAC and GSH, and positively with MDA level. Grip-strength, rotarod and Y-maze findings were inversely correlated with brain free Cu and MDA levels and positively with GSH and TAC levels.The oxidative stress was highest in liver followed by brain and kidney after oral CuSO4 exposure in a rat model. These levels correlated with the respective organ dysfunction and tissue free Cu concentration.

Neuroprotective Effects of Pine Bark and Aloe vera on the Locomotor Activity in Focal Cerebral Ischemia: Possible Antioxidant Mechanisms

Objective: Free radical induced neural damage is concerned in brain ischemia and antioxidants are reported to have neuroprotective activity. We investigated the protective effects of antioxidant plants that are Pine Bark and Aloe vera extracts against movement activity and oxidative stress in ischemia rats. Materials and methods: Fifty rats were randomly separated into six groups (n=7); control group, middle cerebral artery occlusion (MCAO), MCAO+pine bark 1 (25 mg/kg), MCAO+pine bark 2 (05 mg/kg), MCAO+Aloe vera 1 (50 mg/kg), MCAO+Aloe vera 2 (100 mg/kg). All extracts were infused (IP) to animals for 14 days before MCAO. Then the middle cerebral artery of rats was occluded for 2 h and reperfused for 22 h. The brain malondialdehyde (MDA), Thiol levels and locomotor activity on rotarod test were assessed. Results: The MDA levels of brain were non-significantly increased in MCAO group vs control group. The thiol level of brain was significantly decreased in MCAO group compared to control group (p<0.005). The thiol level in groups pine bark 2 and Aloe vera 2 increased significantly vs MCAO group (p<0.01). The time stands rates on rotarod in MCAO group decreased significantly compared to control group. It was also increased significantly in pine bark 1 and pine bark 2 groups vs MCAO group (p<0.005). Time stands rates on rotarod in Aloe vera 1 and Aloe vera 2 groups were increased significantly compared to MCAO group (p<0.005). Conclusion: Increasing endogenous antioxidant enzymatic activities indicate that Aloe vera and pine bark have neuroprotective role. Thus, herbal treatment of pine bark and Aloe vera may improve the function of ischemiareperfusion brain injury related disorders.

Chronical sleep interruption-induced cognitive decline assessed by a metabolomics method

Good sleep is necessary for optimal health, especially for mental health. Insomnia, sleep deprivation will make your ability to learn and memory impaired. Nevertheless, the underlying pathophysiological mechanism of sleep disorders-induced cognitive decline is still largely unknown. In this study, the sleep deprivation of animal model was induced by chronical sleep interruption (CSI), the behavioral tests, biochemical index determinations, and a liquid chromatography-mass spectrometry (LC–MS) based serum metabolic profiling analysis were performed to explore the effects of CSI on cognitive function and the underlying mechanisms. After 14-days CSI, the cognitive function of the mice was evaluated by new objects preference (NOP) task and temporal order judgment (TOJ) task. Serum corticosterone (CORT), and brain Malondialdehyde (MDA), Superoxide Dismutase (SOD), and Catalase (CAT) levels were determined by ELISA kits. Data were analyzed by Principal Component Analysis (PCA), Partial Least Squares project to latent structures-Discriminant Analysis (PLS-DA), and Student’s t-test. We found that the cognitive function of the mice was significantly affected by CSI. Besides, levels of CORT and MDA were higher, and SOD and CAT were lower in CSI mice than those of control. Obvious body weight loss of CSI mice was also observed. Thirteen potential serum biomarkers including choline, valine, uric acid, allantoic acid, carnitines, and retinoids were identified. Affected metabolic pathways involve metabolism of purine, retinoid, lipids, and amino acid. These results showed that CSI can damage the cognitive performance notably. The cognitive decline may ascribe to excessive oxidative stress and a series of disturbed metabolic pathways.

Brain dysfunctions in Wistar rats exposed to municipal landfill leachates

Brain damage induced by Olusosun and Aba-Eku municipal landfill leachates was investigated in Wistar rats. Male rats were orally exposed to 1–25% concentrations of the leachates for 30 days. Catalase (CAT) and superoxide dismutase (SOD) activities, and malondialdehyde (MDA) concentrations in the brain and serum of rats were evaluated; body and brain weight gain and histopathology were examined. There was significant (p < 0.05) decrease in body weight gain and SOD activity but increase in absolute and relative brain weight gain, MDA concentration and CAT activity in both brain and serum of treated rats. The biochemical parameters, which were more altered in the brain than serum, corroborated the neurologic lesions; neurodegeneration of purkinje cells with loss of dendrites, perineural vacuolations of the neuronal cytoplasm (spongiosis) and neuronal necrosis in the brain. The concentrations of Cr, Cu, Pb, As, Cd, Mn, Ni, sulphates, ammonia, chloride and phosphate in the leachate samples were above standard permissible limits. The interactions of the neurotoxic constituents of the leachates induced the observed brain damage in the rats via oxidative damage. This suggests health risk in wildlife and human populations.

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.

Protective effects of chitosan and its water-soluble derivatives against lead-induced oxidative stress in mice

Lead-induced oxidative stress was generated in mice under lead exposure, and the antioxidant activity of chitosan (CS) and its water-soluble derivatives was compared in vivo. The results indicated that there was significant difference (P<0.05) for the biochemical variables of lead-treated groups. After lead exposure, the contents of reduced glutathione (GSH) and total thiols (T-SH) in blood and tissues decreased, and the contents of protein oxidation, oxidized glutathione (GSSG), malondialdehyde (MDA) and reactive oxygen species (ROS) increased compared with the control group. Administration of CS and its derivatives made for the removal of lead from blood and tissues, especially for hydroxypropyl chitosan (HPCS) and quaternary ammonium salt of chitosan (HACC). And the changed biochemical variables showed recovery with different degrees, which indicated that CS and its derivatives were helpful for alleviating lead-induced oxidation damage in vivo. But the antioxidant activity for different CS was different, followed by HPCS>HACC>carboxymethyl chitosan (CMCS)>CS, which was in close with the introduction of different substituent groups. In particular, for the dietary of HPCS, there was significant recovery for the changed biochemical variables (P<0.05) in mice after lead exposure, except GSSG in kidney and MDA in brain.

Protective effects of low molecular weight chondroitin sulfate on amyloid beta (Aβ)-induced damage in vitro and in vivo

In the present study, we investigated the effects of low molecular weight chondroitin sulfate (LMWCS) on amyloid beta (Aβ)-induced neurotoxicity in vitro and in vivo. The in vitro results showed that LMWCS blocked Aβ25–35-induced cell viability loss and apoptosis, decreased intracellular calcium concentration, reactive oxygen species (ROS) levels, the mitochondrial membrane potential (MMP) depolarization, and the protein expression of Caspase-3. During in vivo experiments, LMWCS improved the cognitive impairment induced by Aβ1–40, increased the level of choline acetyltransferase (ChAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and decreased the level of malondialdehyde (MDA) and acetylcholinesterase (AChE) in the mouse brain. Moreover, LMWCS decreased the density of pyramidal cells of CA1 regions, and suppressed the protein expression of Bax/Bcl-2 and Caspase-3, -9 in the hippocampus of mice. In conclusion, LMWCS possessed neuroprotective properties against toxic effects induced by Aβ peptides both in vitro and in vivo, which might be related to anti-apoptotic activity. LMWCS might be a useful preventive and therapeutic compound for Alzheimer’s disease.

The Effects of transcranial ultrasound stimulation on motor functioning and anti-oxidative capacity in mice with Parkinson's disease

Objective To investigate the effects of transcranial ultrasound stimulation (TUS) on the motor functioning and anti-oxidative capacity of mice with Parkinson's disease (PD). Methods Thirty-two inbred C57BL male mice were randomized into a normal control group, a model group, a sham TUS group and a TUS group (n=8 for each group) according to a random number table. A PD model was induced in the mice of the model, sham TUS and TUS groups by injecting 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) at 20 mg/kg intraperitoneally, while those in the normal control group were given saline. Low intensity (1 W) focused ultrasound (LIFU) at a frequency of 0.5 MHz was then applied to stimulate the nigra region, except for the mice in the sham TUS group, which were treated with the same procedure but with no ultrasound output. A pole climbing test was carried out before, 2 weeks and 5 weeks after the injection of the MPTP. After 5 weeks the animals were sacrificed and the whole brain malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) content were measured. Results No significant differences in in pole climbing scores were observed among the four groups before the MPTP injections. However, the average value decreased significantly to (4.30±1.19), (4.40±0.23) and (4.80±0.23) for the model, sham TUS and TUS groups respectively 2 weeks after the injection. It then rose to (5.12±0.83) and (5.51±1.21) for the first two groups 3 weeks later, but was still lower that before the injection. After 5 weeks the TUS group's average score was significantly higher than 3 weeks earlier and than that of the model group and the sham TUS group. Compared with the control group, the other groups' average scores were all lower 2 weeks after MPTP injection, and those of the model and the sham TUS groups remained so 5 weeks after the injection. Five weeks after the injection, the average MDA content of the model group (10.2±1.1 nmol/ml) and the sham TUS group (9.4±1.3 nmol/ml) were significantly higher than the normal control group (4.5±0.8 nmol/ml), as well as the TUS group (6.8±0.9 nmol/ml). However, GSH-Px enzyme activity in the model group (100±35.4 U/mgprot) and the sham US group (444±24.9 U/mgprot) was significantly lower than that in the normal control group (1262.5±53 U/mgprot), together with the TUS group (1047.3±77.8 U/mgprot). Conclusion TUS can improve motor function in PD, at least in mice. This may be due to its anti-oxidative capacity. Key words: Ultrasound; Parkinson's disease; Motor function; Antioxidants; Brain