Stress In Different Brain Regions Research Articles

Neuroprotective Effect of N-acetylcysteine Against Monocrotophos-Induced Oxidative Stress in Different Brain Regions of Rats.

Monocrotophos (MCP) is systemic organophosphate insecticide used against crop pests. It is reported to cause mammalian toxicity through both acute and chronic exposure. In the present study, we have shown the protective role of N-acetylcysteine (NAC) against MCP-induced oxidative stress in frontal cortex, corpus striatum and hippocampus brain regions of rats. Male Albino Wistar rats were divided into control, NAC-treated, MCP and NAC + MCP-treated groups. An oral dose of MCP (0.9mg/kg b.wt) and NAC (200mg/kg b.wt) was administered for 28days. Results showed an increase in lipid peroxidation (LPO) and protein oxidation followed by decreased antioxidant enzymes after 28days of MCP exposure. Histopathological analysis showed that monocrotophos exposure caused neurodegenerative changes as evident by neurons with dystrophic changes in the form of shrunken hyperchromatic nuclei in all the regions of the rat brain. N-acetylcysteine supplementation to MCP-treated rats showed a reduction in oxidative stress and ameliorated cellular alterations in all of the three regions. The results of the study indicate that N-acetylcysteine offers neuroprotection by improving antioxidant response and decreasing oxidative stress in different regions of the rat brain.

Influence of Age on Sleep Deprivation Induced Oxidative Stress in Different Brain Regions of Young and Old Rats

Sleep plays a crucial role in maintaining brain function and neuronal signalling and helps maintain overall health of the individuals. Sleep deprivation (SD) disturbs the circadian physiology and exerts a negative impact on brain and behavioural functions. The aim of the present study was to investigate the SD induced oxidative stress with advancing age in different brain regions. In the present study, young and old rats were taken as control and experimental rats (n=6) respectively. Lipid peroxidation and protein oxidation significantly increased (p<0.05) and reduces antioxidant levels in experimental young and old rats. The most affected part of the brain was hippocampus followed by cerebral cortex. The biochemical changes observed in SD treated young rats were comparable to those of untreated old control rats. Therefore, SD may play a role in the premature aging of animals.

Silica Nanoparticles Induced Oxidative Stress in Different Brain Regions of Male Albino Rats

Silica nanoparticles (SiNPs) are encapsulated in an ecological platform has been planned to supply many benefits, and blood vessels used as laser-tissue-soldering within the brain, and during the course of the degradation, SiNPs given to the discharged into an encircling of the brain tissue. The goal of this modern research was to examine likely to the silicon dioxide nanoparticles are categorized in the microglial cells and uptake the cellular mechanism(s), and additionally these impacts on autophagy and inflammatory cytokines, and also it's been found in depth applications in medical specialty and biotechnological fields, for example, bio imaging, medical diagnostics, gene therapy, drug delivery, photodynamic therapy biomolecule detection and bio-imaging. It has also been added to the raising of the industrial mechanism to the exposure of silicon dioxide nanoparticles, throughout the manufacturing, transportation, storage, and consumers that are obviously increased used by human exposure and environmental burden. The purpose of this work was to examine the neurotoxicity of two different dosages (40 and 80 mg/kg body weight) of silica nanoparticles (SiNPs) in male albino rats for 14 days by intraperitoneal exposure. The neurobehavioral and neurochemical changes were analyzed. Spontaneous motor activity, catalepsy, gait and muscle incoordination were assessed. There after the brain was removed for the examination of lipid peroxide level and antioxidant enzymes (SOD and CAT). Our results indicated the SNPs could passed from the blood-brain-barrier into the brain, and essentially it increases the concentration of lipid peroxide levels and reduce the activity of SOD and CAT and also its reduce the behavioral activity were seen. The maximum changes were observed in rats, who received 80 mg/kg body weight doses. It can be concluded that neuronal toxicity of silica nanoparticles could be related to the amount of the particles and the oxidative stress could be ............

Distress Regulates Different Pathways in the Brain of Common Carp: A Preliminary Study.

Simple SummaryThe aquaculture sector provides for nearly half of the world’s seafood consumption, thanks to its large expansion over the last 30 years. Despite this intense growth, clear guidelines for responsible practices and animal wellbeing are lacking. Gene expression studies are a fundamental tool for understanding welfare, but stress-markers in aquaculture fish species are poorly studied. In addition, the biostatistical analysis of gene expression data is not trivial, and this study applies different statistical methods in order to evaluate potential differences in the gene expression levels between control fish and fish acutely stressed by exposure to air.In this study, a stress trial was conducted with common carp, one of the most important species in aquaculture worldwide, to identify relevant gene regulation pathways in different areas of the brain. Acute distress due to exposure to air significantly activated the expression of the immediate early gene c-fos in the telencephalon. In addition, evidence for regulation of the two corticotropin-releasing factor (crf) genes in relation to their binding protein (corticotropin-releasing hormone-binding protein, crh-bp) is presented in this preliminary study. Inferences on the effects of due to exposure to air were obtained by using point estimation, which allows the prediction of a single value. This constitutes the best description to date of the previously generally unknown effects of stress in different brain regions in carp. Furthermore, principal component analyses were performed to reveal possible regulation patterns in the different regions of the fish brain. In conclusion, these preliminary studies on gene regulation in the carp brain that has been influenced by exposure to a stressor reveal that a number of genes may be successfully used as markers for exposure to unfavourable conditions.

Increase of mtDNA number and its mutant copies in rat brain after exposure to 150 MeV protons

Proton beam therapy is widely used for treating brain tumor. Despite the efficacy of treatment, the use of this therapy has met some limitations associated with possible damage to normal brain tissues located beyond the tumor site. In this context, the exploration of the harmful effects of protons on the normal brain tissues is of particular interest. We have investigated changes in the total mitochondrial DNA (mtDNA) copy number and identified mtDNA mutant copies in three brain regions (the hippocampus, cortex and cerebellum) of rats after irradiation their whole-head with 150MeV protons at doses of 3 and 5Gy. The study was performed in 2-months old male Spraque Dawley rats (n = 5 each group). The mtDNA copy numbers were determined by real-time PCR. The level of mtDNA heteroplasmy was estimated using Surveyor nuclease technology. Our results show that after head exposure to protons, levels of mtDNA copy number in three rat brain regions increase significantly as the levels of mtDNA mutant copies increase. The most significant elevation is observed in the hippocampus. In conclusion, an increase in mtDNA mutant copies may contribute to mitochondrial dysfunction accompanied by increased oxidative stress in different brain regions and promote the development of neurodegenerative diseases and the induction of carcinogenesis.

Combination of Zizyphus jujuba and silymarin showed better neuroprotective effect as compared to single agent in MCAo-induced focal cerebral ischemia in rats

Ethnopharmacological relevanceTraditionally, Zizyphus jujuba is used for anticonvulsant, hypnotic-sedative, anxiolytic, tranquilizer, antioxidant and anti-inflammatory properties. Likewise silymarin is popularly used for its potent antioxidant and hepatoprotective effects. Stroke being a multifactorial disease with unsatisfactory treatment outcomes, necessitates development of multimodal therapeutic interventions. Thus, we evaluated the therapeutic benefits of herbal combination of Z. jujuba and silymarin in a focal cerebral ischemia model. Aim of the studyTo evaluate the neuroprotective potential of hydroalcoholic extract of Z. jujuba (HEZJ) fruit and silymarin alone and in combination in middle cerebral artery occlusion (MCAo) model of focal cerebral ischemia in rats. Materials and methodsMale Wistar rats were pretreated with HEZJ (100, 250 and 500mg/kg, p.o.) or silymarin (250mg/kg, p.o.) for 3 days prior to induction of MCAo. Neurological deficit score, motor impairment and cerebral infarction were assessed 24h following MCAo. HEZJ (250mg/kg) co-administered with silymarin (250mg/kg) for 3 days prior to induction of MCAo was also evaluated for above parameters and oxidative stress. Malondialdehyde (MDA), nitric oxide (NO) and superoxide dismutase (SOD) levels in the cortex, striatum and hippocampal brain regions were estimated 24h post MCAo. ResultsPretreatment with HEZJ and silymarin reduced the neurological deficit score, motor impairment and cerebral infarction volume. HEZJ and silymarin pretreatment also ameliorated the oxidative stress in different brain regions, which was evident from increased SOD levels, decreased MDA and NO levels as compared to MCAo control rats. Interestingly neuroprotective efficacy was potentiated by pretreatment with HEZJ and silymarin combination. ConclusionPretreatment with HEZJ and silymarin combination was observed to have better neuroprotection mediated via amelioration of oxidative stress in the focal cerebral ischemia model.

Effect of Chronic Treatment with Conventional and Organic Purple Grape Juices (Vitis labrusca) on Rats Fed with High-Fat Diet

Serra Gaucha is described as the most important wine region of Brazil. Regarding cultivars widespread in the Serra Gaucha, about 90 % of the area is occupied by vines of Vitis labrusca that is the most important specie used in grape juice production. The objective of this study was to investigate the antioxidant and neuroprotective effect of chronic intake of purple grape juice (organic and conventional) from Bordo variety (V. labrusca) on oxidative stress in different brain regions of rats supplemented with high-fat diet (HFD) for 3 months. A total of 40 male rats were randomly divided into 4 groups. Group 1 received a standard diet and water, group 2 HFD and water, group 3 HFD and conventional grape juice (CGJ), and group 4 HFD and organic grape juice (OGJ). All groups had free access to food and drink and after 3 months of treatment the rats were euthanized by decapitation and the cerebral cortex, hippocampus and cerebellum isolated and homogenized on ice for oxidative stress analysis. We observed that the consumption of calories in HFD and control groups, were higher than the groups supplemented with HFD and grape juices and that HFD diet group gain more weight than the other animals. Our results also demonstrated that HDF enhanced lipid peroxidation (TBARS) and protein damage (carbonyl) in cerebral cortex and hippocampus, reduced the non-enzymatic antioxidants defenses (sulfhydryl) in cerebral cortex and cerebellum, reduced catalase and superoxide dismutase activities in all brain tissues and enhanced nitric oxide production in all cerebral tissues. CGJ and OGJ were able to ameliorate these oxidative alterations, being OGJ more effective in this protection. Therefore, grape juices could be useful in the treatment of some neurodegenerative diseases associated with oxidative damage.

Neuroprotective effect of curcumin on okadaic acid induced memory impairment in mice

Okadaic acid (OKA) has been observed to cause memory impairment in human subjects having seafood contaminated with dinoflagellate (Helicondria okadai). OKA induces tau hyperphosphorylation and oxidative stress leading to memory impairment as our previous study has shown. Curcumin a natural antioxidant has demonstrated neuroprotection in various models of neurodegeneration. However, the effect of curcumin has not been explored in OKA induced memory impairment. Therefore, present study evaluated the effect of curcumin on OKA (100ng, intracerebrally) induced memory impairment in male Swiss albino mice as evaluated in Morris water maze (MWM) and passive avoidance tests (PAT). OKA administration resulted in memory impairment with a decreased cerebral blood flow (CBF) (measured by laser doppler flowmetry), ATP level and increased mitochondrial (Ca2+)i, neuroinflammation (increased TNF-α, IL-1β, COX-2 and GFAP), oxidative-nitrosative stress, increased Caspase-9 and cholinergic dysfunction (decreased AChE activity/expression and α7 nicotinic acetylcholine receptor expression) in cerebral cortex and hippocampus of mice brain. Oral administration of curcumin (50mg/kg) for 13 days significantly improved memory function in both MWM and PAT along with brain energy metabolism, CBF and cholinergic function. It decreased mitochondrial (Ca2+)i, and ameliorated neuroinflammation and oxidative-nitrostative stress in different brain regions of OKA treated mice. Curcumin also inhibited astrocyte activation as evidenced by decreased GFAP expression. This neuroprotective effect of curcumin is due to its potent anti-oxidant action thus confirming previous studies. Therefore, use of curcumin should be encouraged in people consuming sea food (contaminated with dinoflagellates) to prevent cognitive impairment.

Effect of Chronic Administration of the Vinyl Chalcogenide 3-Methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on Oxidative Stress in Different Brain Areas of Rats

Selenium (Se) is an essential mineral for mammals. It is a nutrient related to the complex metabolic and enzymatic functions. Although Se has important physiological functions in the cells, organic compounds of Se can be extremely toxic, and may affect the central nervous system. This study aims to investigate the effect of the chronic treatment with the vinyl chalcogenide 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on some parameters of oxidative stress in the brain of rats. Animals received the vinyl chalcogenide (125, 250 or 500 μg/kg body weight) intraperitoneally once a day during 30 days. The cerebral cortex, the hippocampus, and the cerebellum were dissected and homogenized in KCl. Afterward, thiobarbituric acid reactive substances (TBARS), carbonyl, sulfhydryl, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured in the brain. Results showed that the organoselenium enhanced TBARS in the cerebral cortex of rats but the compound was not able to change carbonyl levels. Furthermore, the organoselenium reduced thiol groups measured by the sulfhydryl assay in all tissues studied. The activity of the antioxidant enzyme CAT was increased by the organochalcogen in the cerebral cortex and in the cerebellum, and the activity of SOD was increased in the hippocampus. On the other hand, the activity of the antioxidant enzyme GPx was reduced in all brain structures. Our findings indicate that this organoselenium compound induces oxidative stress in different brain regions of rats, corroborating to the fact that this tissue is a potential target for organochalcogen action.

The Effect of Ginkgo biloba extract (EGb 761) on parameters of oxidative stress in different regions of aging rat brains after acute hypoxia

Neurodegenerative processes of aging seem to be associated with oxidative stress by reactive oxygen species (ROS). This study investigates the influence of age and of acute respiratoric hypoxia on parameters of oxidative stress in different brain regions of Wistar rats and the protective effects of Ginkgo extract (EGb 761) as a radical scavenger. Biopsies of frontal and temporal cortices, the cerebellum, and the brainstem of young and old rats (each group n=6-8: normoxic - hypoxic; unprotected - EGb-protected) were analyzed for malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, glutathione (GSH) content, and creatine kinase (CK) activity. Experimental hypoxia: downregulation of oxygen partial pressure to 5 vol. % for 20 minutes. EGb administration: daily 100 mg/kg of body weight in drinking water for 3 months. Effects of age: While most oxidative stress parameters in the temporal cortex, the cerebellum, and the brainstem are increased, this is not the case in the frontal cortex; after additional hypoxia SOD and GSH are diminished in the temporal cortex and the brainstem of old rats. EGb treatment causes contradictory alterations in young, old, and hypoxic brain regions. Minor effects are seen in old hypoxic brains, while there are some protective effects in old normoxic brainstems and cerebellums. The old brain appears to adapt appropriately to chronic oxidative stress and to the specific conditions of shortterm hypoxia. EGb's protective effect is especially notable in the brainstem and the cerebellum.

Tempol attenuates cocaine-induced death of PC12 cells through decreased oxidative damage

The association between cocaine administration and induction of oxidative stress in different brain regions suggests that oxidative damage is an important factor participating in cocaine disruption of normal central nervous system functions. In order to deal with this topic, brain penetrating exogenous antioxidants were suggested as a tool to prevent cocaine-induced oxidative damage and behavioral changes. Lately, we have shown that Tempol, a stable nitroxide radical reduced oxidative damage and attenuated the development and expression of cocaine psychomotor sensitization. To examine whether nitroxides, represented by Tempol, can exhibit protective effects against cocaine-induced cell death and to elucidate the molecular mechanism of cocaine-induced oxidative damage, we used the well established PC12 cell line model. The results showed that (1) cocaine induced cell death in a dose-dependent manner (2) and that it was reduced significantly by the stable nitroxide radical Tempol. Furthermore, (3) Tempol significantly inhibited oxidative damage induced by cocaine as reflected by mitochondrial superoxide radical and peroxide enhancement. Finally, (4) Tempol restored the total scavenging capacity which was reduced by cocaine in PC12 cells. Cumulatively, these results suggest that nitroxides such as Tempol can attenuate oxidative damage and cell death induced by cocaine and that PC12 cells can be used as an in vitro model to further investigate the precise molecular mechanism of these compounds.

Protective effects of Nigella sativa oil on propoxur-induced toxicity and oxidative stress in rat brain regions

Propoxur (PPr) is a widely used broad spectrum carbamate insecticide mainly used to control household pests. Because of the widespread use of pesticides for domestic and industrial applications, evaluation of their neurotoxic effects is of major concern to public health. The aim of the present study was to evaluate the possible protective effects of Nigella sativa oil (NSO), an antioxidant agent, against PPr-induced toxicity and oxidative stress in different brain regions of rats including cerebellum, cortex and hippocampus. In the present study, 32 male Sprague–Dawley rats were used and divided into four equal groups. Group 1 was allocated as the control group. Groups 2–4 were orally administered 1 ml/kg/bw/day NSO, 8.51 mg/kg/bw/day PPr or NSO plus PPr, respectively, for 30 days. Lipid peroxidation (LPO), protein carbonyl content (PCC) and acetylcholine esterase activity (AChE) were determined. Enzymatic antioxidant activities [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione- S-transferase (GST)] and non-enzymatic antioxidants [reduced glutathione (GSH)] were determined. PPr treatment significantly increased the levels of LPO, PCC and oxidized glutathione (GSSG) in brain regions. On the contrary, levels of GSH and the activities of SOD, CAT, GSH-Px, GST and AChE were significantly decreased. NSO treatment to PPr intoxicated rats restored such biochemical parameters to within control levels except GST activity, emphasizing its antioxidant role. We conclude that NSO significantly reduces PPr-induced toxicity and oxidative stress in rat brain regions via a free radicals scavenging mechanism.

Effect of melatonin on neuroinflammation and acetylcholinesterase activity induced by LPS in rat brain

Melatonin, which plays an important role in circadian rhythm regulation, is highly potent endogenous free radical scavenger and antioxidant. To determine the efficacy of melatonin in neuroinflammation induced by intracerebroventricular (i.c.v.) administration of lipopolysachcharide (LPS, 50 µg), pro-inflammatory cytokines (TNF-α and IL-1β), and markers of oxidative stress (malondialdehyde and reduced glutathione) were studied in different brain regions (striatum, cerebral cortex, hippocampus and hypothalamus) of rat. To study the cholinergic intervention during neuroinflammatory conditions acetylcholinesterase (AChE) enzyme activity was taken as marker of cholinergic activity. Melatonin (5 and 10 mg/kg, p.o.) decreased the LPS induced pro-inflammatory cytokines and oxidative stress in different brain regions. It was also found to inhibit the LPS induced increase in AChE activity. These results suggest the therapeutic potential of melatonin for neuroinflammation which is an integral part of neurodegenerative disorders.

Melatonin alleviates memory deficits and neuronal degeneration induced by intracerebroventricular administration of streptozotocin in rats

In the present study the effect of melatonin on intracerebroventricularly administered streptozotocin (STZ)-induced neurodegeneration was investigated in rats. STZ (3 mg/kg), administered twice with an interval of 48 h between the two doses, showed impairment in spatial memory tested by water maze test after 14 days of 1st dose. Administration of melatonin (2.5, 5.0 and 10 mg/kg, i.p.) was started 1 h prior to 1st dose of STZ and continued up to 14 days. Glutathione and malondialdehyde were used as biochemical markers of oxidative stress in different brain regions. Histopathological changes were examined by using hematoxylin and eosin stain. STZ administration caused significant decrease in glutathione and increase in malondialdehyde as compared to control and artificial Cerebrospinal Fluid treated rats indicating oxidative stress. Brain sections of STZ-treated rats showed increased vacuoles in the periventricular cortical area, damaged periventricular cells and damaged cells in the hippocampal CA4 region as compared to control and artificial Cerebrospinal Fluid treated groups. Melatonin treatment significantly attenuated the effect of STZ-induced oxidative stress and histopathological changes. The results indicate that melatonin is effective in providing protection against memory deficit, oxidative stress and neuronal damage induced by STZ.

Interactions Between Chronic Stress and Chronic Consumption of Caffeine on the Enzymatic Antioxidant System

We studied the effect of chronic caffeine on parameters related to oxidative stress in different brain regions of stressed and non-stressed rats. Wistar rats were divided into three groups: control (receiving water), caffeine 0.3 g/L and caffeine 1.0 g/L (in the drinking water). These groups were subdivided into non-stressed and stressed (repeated restraint stress during 40 days). Lipid peroxide levels and the total radical-trapping potential were assessed, as well as antioxidant enzyme activities superoxide dismutase, gluthatione peroxidase, and catalase in hippocampus, striatum and cerebral cortex. Results showed interactions between stress and caffeine, especially in the cerebral cortex, since caffeine increased the activity of some antioxidant enzymes, but not in stressed animals. We concluded that chronic administration of caffeine led, in some cases, to increased activity of antioxidant enzymes. However, these effects were not observed in the stressed animals.

A study of brain insulin receptors, AChE activity and oxidative stress in rat model of ICV STZ induced dementia

In the present study, role of brain insulin receptors (IRs) in memory functions and its correlation with acetylcholinesterase (AChE) activity and oxidative stress in different brain regions were investigated in intracerebroventricular (ICV) streptozotocin (STZ) induced dementia model. Rats were treated with STZ (3 mg/kg, ICV) on day 1 and 3. Donepezil (5 mg/kg po) and melatonin (20 mg/kg ip) were administered in pre- and post-treatment schedules. Morris water maze test was done on day 14 and animals were sacrificed on day 21 from 1st STZ injection. Memory deficit was found in STZ group as indicated by no significant decrease in latency time antagonized by donepezil and melatonin. IR protein level was found significantly increased in trained group as compared to control, whereas STZ decreased IR level significantly as compared to trained rats in hippocampus which indicates that IR is associated with memory functions. STZ induced decrease in IR was reversed by melatonin but not by donepezil. Melatonin per se did not show any significant change in IR level as compared to control. AChE activity (DS and SS fraction) was found to be increased in hippocampus in STZ group as compared to trained which was inhibited by donepezil and melatonin. Increase in MDA level and decrease in GSH level were obtained in STZ group indicating oxidative stress, which was attenuated by donepezil and melatonin. Effectiveness of antioxidant, melatonin but not of anti-cholinesterase, donepezil against STZ induced changes in IR indicates that IR is more affected with oxidative stress than cholinergic changes.

The modulatory effects of ellagic acid and vitamin e succinate on TCDD‐induced oxidative stress in different brain regions of rats after subchronic exposure

AbstractThe original article to which this Erratum was published online 27 November 2004 in Wiley InterScience

The modulatory effects of ellagic acid and vitamin E succinate on TCDD-induced oxidative stress in different brain regions of rats after subchronic exposure.

The effects of ellagic acid (EA) and vitamin E succinate (VES) on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced oxidative stress in different brain regions of rats have been studied after subchronic exposure to the compounds. TCDD was administered to groups of rats at a dose of 46 ng/kg/day for 90 days. EA and VES were administered to groups of rats, either separately or simultaneously with TCDD, every other day for 90 days. At the end of the treatment period, animals were sacrificed and brains were dissected to cerebral cortex (Cc), hippocampus (H), cerebellum (C), and brain stem (Bs), and were assayed for production of superoxide anion (SA), lipid peroxidation (LP), and DNA single-strand breaks (SSBs). While TCDD administration to rats resulted in significant production of SA, LP, and DNA SSBs in Cc and H, simultaneous administration of VES or EA with the xenobiotics resulted in significant protection against those effects. The results also indicate that VES provided a better protyection against TCDD-induced effects in brains when compared with EA.

Beneficial effect of combined administration of some naturally occurring antioxidants (vitamins) and thiol chelators in the treatment of chronic lead intoxication

Ameliorative effects of few naturally occurring antioxidants like ascorbic acid (vitamin C), α-tocopherol (vitamin E) either alone or in combination with meso-2,3-dimercaptosuccinic acid (DMSA) or monoisoamyl DMSA (MiADMSA), on parameters indicative of oxidative stress in the liver, kidney, brain and blood of lead-exposed rats were studied. Male Wistar rats were exposed to 0.1% lead acetate in drinking water for 3 months and treated thereafter with DMSA or its analogue MiADMSA (50 mg/kg, intraperitoneally), either individually or in combination with vitamin E (5 mg/kg, intramuscularly) or vitamin C (25 mg/kg, orally) once daily for 5 days. The effects of these treatments in influencing the lead-induced alterations in haem synthesis pathway, hepatic, renal and brain oxidative stress and lead concentration from the soft tissues were investigated. Exposure to lead produced a significant inhibition of δ-aminolevulinic acid dehydratase (ALAD) activity from 8.44±0.26 in control animals to 1.76±0.32 in lead control, reduction in glutathione (GSH) from 3.56±0.14 to 2.57±0.25 and an increase in zinc protoporphyrin level from 62.0±3.9 to 170±10.7 in blood, suggesting altered haem synthesis pathway. Both the thiol chelators and the two vitamins were able to increase blood ALAD activity towards normal, however, GSH level responded favorably only to the two thiol chelators. The most prominent effect on blood ALAD activity was, however, observed when MiADMSA was co-administered with vitamin C (7.51±0.17). Lead exposure produced a significant depletion of hepatic GSH from 4.59±0.78 in control animals to 2.27±0.47 in lead controls and catalase activity from 100±3.4 to 22.1±0.25, while oxidized glutathione (GSSG; 0.34±0.05 to 2.05±0.25), thiobarbituric acid reactive substance (TBARS; 1.70±0.45 to 5.22±0.50) and glutathione peroxidase (GPx) levels (3.41±0.09 to 6.17±0.65) increased significantly, pointing to hepatic oxidative stress. Altered, reduced and oxidized GSH levels showed significant recovery after MiADMSA and DMSA administration while, vitamins E and C were effective in reducing GSSG and TBARS levels and increasing catalase activity. Administration of MiADMSA alone and the combined administration of vitamin C along with DMSA and MiADMSA were most effective in increasing hepatic GSH levels to 4.88±0.14, 4.09±0.12 and 4.30±0.06, respectively. Hepatic catalase also reached near normal level in animals co-administered vitamin C with DMSA or MiADMSA (82.5±4.5 and 84.2±3.5, respectively). Combined treatments with vitamins and the thiol chelators were also able to effectively reduce lead-induced decrease in renal catalase activity and increase in TBARS and GPx level. Combination therapy, however, was unable to provide an effective reversal in the altered parameters indicative of oxidative stress in different brain regions, except in catalase activity. The result also suggests a beneficial role of vitamin E when administered along with the thiol chelators (particularly with MiADMSA) in reducing body lead burden. Blood lead concentration was reduced from 13.3±0.11 in lead control to 0.3±0.01 in MiADMSA plus vitamin E-treated rats. Liver and kidney lead concentration also showed a most prominent decrease in MiADMSA plus vitamin E co-administered rats (5.29±0.16 to 0.63±0.02 and 14.1±0.21 to 1.51±0.13 in liver and kidney, respectively). These results thus suggest that vitamin C administration during chelation with DMSA/MiADMSA was significantly beneficial in reducing oxidative stress however, it had little or no additive effect on the depletion of lead compared with the effect of chelators alone. Thus, the co-administration of vitamin E during chelation treatment with DMSA or MiADMSA could be recommended for achieving optimum effects of chelation therapy.

Ketogenic diet increases glutathione peroxidase activity in rat hippocampus.

Ketogenic diets have been used in the treatment of refractory childhood epilepsy for almost 80 years; however, we know little about the underlying biochemical basis of their action. In this study, we evaluate oxidative stress in different brain regions from Wistar rats fed a ketogenic diet. Cerebral cortex appears to have not been affected by this diet, and cerebellum presented a decrease in antioxidant capacity measured by a luminol oxidation assay without changes in antioxidant enzyme activities--glutathione peroxidase, catalase, and superoxide dismutase. In the hippocampus, however, we observed an increase in antioxidant activity accompanied by an increase of glutathione peroxidase (about 4 times) and no changes in lipoperoxidation levels. We suggest that the higher activity of this enzyme induced by ketogenic diet in hippocampus might contribute to protect this structure from neurodegenerative sequelae of convulsive disorders.