Oxidative Stress In Rat Brain Research Articles

Neurotoxicity of hexaconazole on rat brain: The aspect of biological rhythm

Hexaconazole is a widely used and frequently detected fungicide which is also reported to be persistent in environment. The toxicity of Hex to non-organisms such as reproductive toxicity, endocrine disrupting toxicity, and carcinogenic toxicity had been reported. However, study on the Hex-induced neurotoxicity is rare and the mechanism is still unclear. Therefore, in this study, environmental related concentrations of Hex were chosen to investigate the effects of Hex on nervous system from the aspect of biological rhythm under 90 d sub-chronic exposure. The results showed that Hex significantly affected the cognitive function of rats resulting in the deterioration of learning and memory ability and induced oxidative stress in rat brain. Moreover, the notable changes of neurotransmitters in rat brain suggested the disorder of nerve signaling conduction induced by Hex. The influence of Hex on biological rhythm was further detected which showed that levels of rhythm regulatory genes and proteins significantly disturbed at four monitored time periods. Based on these results, it was supposed that the underlying mechanism of Hex-induced cognitive dysfunction might through oxidative stress pathway. Our findings could systematically and comprehensively clarify the effects of Hex on nervous system and were helpful for prevention neurological diseases induced by triazole pesticides.

Ginger (Zingiber officinale) attenuates the neurotoxicity in rats induced by organophosphate pesticide

BackgroundWe are exposed to different chemicals in various ways in our daily life, and these can be toxic at minute concentrations. The pesticides used for different purposes are also toxic and may pose threat to life by inducing oxidative stress. Dichlorvos (DDVP) is an organophosphate pesticide used for various purposes and is also reported to be toxic. In this study, the neurotoxicity of DDVP exposure was studied. The role of ginger, Zingiber officinale (ZO), was also evaluated against the neurotoxic effects of DDVP. Forty-eight Wistar rats of both the sexes were used in this study. The rats were exposed to DDVP and post-treatment with ZO was given. The oxidative stress in terms of lipid peroxidation (LPO), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) levels were estimated after exposure and treatment.ResultsDDVP resulted in oxidative stress, evidenced by enhanced LPO level. The simultaneous reductions in other non-enzymatic and enzymatic antioxidants were reported. The post-treatment with ZO led to a reduction in oxidative stress in rat brains. The levels of SOD, CAT, GSH, GR, and GPx were increased whereas declined levels of LPO were reported after treatment.ConclusionHence, ginger can help mitigate the pesticide toxicity through the up-regulation of antioxidant levels.

Oleic acid reduces oxidative stress in rat brain induced by some anticancer drugs

Oleic acid (OA) is a monounsaturated compound with many health-benefitting properties such as obesity prevention, increased insulin sensitivity, antihypertensive and immune-boosting properties, etc. The aim of this study was to analyze the effect of oleic acid (OA) and some anticancer drugs against oxidative damage induced by nitropropionic acid (NPA) in rat brain. Six groups of Wistar rats were treated as follows: Group 1, (control); group 2, OA; group 3, NPA + OA; group 4, cyclophosphamide (CPP) + OA; group 5, daunorubicin (DRB) + OA; and group 6, dexrazoxane (DXZ) + OA. All compounds were administered intraperitoneally route, every 24 h for 5 days. Their brains were extracted to measure lipoperoxidation (TBARS), H2O2, Ca+2, Mg+2 ATPase activity, glutathione (GSH) and dopamine. Glucose, hemoglobin and triglycerides were measured in blood. In cortex GSH increased in all groups, except in group 2, the group 4 showed the highest increase of this biomarker. TBARS decrease, and dopamine increase in all regions of groups 4, 5 and 6. H2O2 increased only in cerebellum/medulla oblongata of group 5 and 6. ATPase expression decreased in striatum of group 4. Glucose increased in group 6, and hemoglobin increased in groups 4 and 5. These results suggest that the increase of dopamine and the antioxidant effect of oleic acid administration during treatment with oncologic agents could result in less brain injury.

The effects of endogenous melatonin on brain tissue oxidative stress induced by photoperiodic alterations and iron overloading in rats

Melatonin is a potent endogenously occurring antioxidant with the pleiotropic activities to neurodegenerative diseases associated with brain oxidative damage. In this study, we examined the prolonged photoperiodic alterations and iron (Fe) overload on melatonin production and brain oxidative stress in rats. The result showed that the 15 days of constant light (CL) exposure did not low the melatonin production but the 15 days of constant darkness (CD) significantly increased serum melatonin level in rats. The Fe treatment in both CL and CD conditions significantly reduced endogenous melatonin levels and increased brain tissue lipid peroxidation. Fe as a toxic transition metal can induce Fenton reaction to generated hydroxyl radical which can damage the neuronal cell membrane and impair the brain antioxidant system. In the current study, we observed the imbalanced antioxidant defense alterations upon Fe treatment in rat brain including the increased levels of alpha-tocopherol (α-T) and total thiols and the reduced melatonin level and catalase (CAT) activity. We speculated that the reduced melatonin level caused by Fe was due to its consumption since melatonin served as a metal chelator and antioxidant. Understanding these aspects enhances knowledge of brain Fe metabolism and its role in neurodegenerative disorders as well as the potential protective effects of melatonin on this metal.

Oxidative stress in rat brain during experimental status epilepticus: effect of antioxidants.

Antioxidants have been proposed as a treatment for diseases of the central nervous system. However, few studies actually studied their effects in the brain. To test central actions of antioxidants, we used the lithium-pilocarpine (Li-Pilo) model of status epilepticus (SE) in the rat in which seizures are accompanied by significant oxidative stress. We used in vivo microdialysis to determine isoprostane levels during SE in real time and brain homogenates for other measures of oxidative stress. Six different antioxidants were tested in acute and preventive experiments (vitamin C, vitamin E, ebselen, resveratrol, n-tert-butyl-α-phenylnitrone and coenzyme Q10). None of the antioxidants had an effect when given acutely during SE. In contrast, when antioxidants were given for 3days prior to seizure induction, vitamins C and E reduced isoprostane formation by 58% and 65%, respectively. Pretreatment with the other antioxidants was ineffective. In brain homogenates prepared after 90min of seizures, SE decreased the ratio of reduced vs. oxidized glutathione (GSH/GSSG ratio) from 60.8 to 7.50 and caused a twofold increase of 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels and protein carbonyls. Pretreatment with vitamin C or vitamin E mitigated these effects and increased the GSH/GSSG ratio to 23.9 and 28.3, respectively. Again, the other antioxidants were not effective. We conclude that preventive treatment with vitamin C or vitamin E ameliorates seizure-induced oxidative damage in the brain. Several well-studied antioxidants were inactive, possibly due to limited brain permeability or a lack of chain-breaking antioxidant activity in hydrophilic compounds.

Andrographis paniculata Ameliorates Hyperammonemia Induced Oxidative Stress in Rat Brain by Activating Antioxidant Enzymes

Andrographis paniculata Ameliorates Hyperammonemia Induced Oxidative Stress in Rat Brain by Activating Antioxidant Enzymes

Exploring the Impacts of Different Music Genres on Oxidative Stress in Rat Brain and Serum

Music reduces emotional stress, relieves anxiety, and is utilized while treating various diseases. The present study explored the impacts of various music genres at different decibels on the oxidation state in the brain tissue and serum. We carried out the study on 42 male Wistar Albino rats. The rats were randomized (six rats in each cage) as a control group and groups exposed to noise, rock music, and slow music at different decibels for 21 days and 4 hours a day. At the end of the experiment, we studied oxidant [malondialdehyde (MDA), nitric oxide, protein carbonyl (PC)] and antioxidant [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px)] parameters in the cerebral cortex, cerebellum, and serum. In the cortex, while MDA levels were low in the 100 dB(A) slow music group, the 50 dB(A) noise and rock music groups had elevated SOD, GSH-Px, and MDA levels when compared to the control group and higher MDA and GSH-Px levels when compared to the 50 dB(A) slow music group. In the cerebellum, although SOD levels did not significantly change, we found MDA and GSH-Px to increase in the 50 dB(A) and 100 dB(A) rock music groups and the 50 dB(A) noise group. Finally, we determined MDA and PC levels to be low and SOD levels to be high in the 50 dB(A) slow music group. Overall, that high dB rock music created oxidative stress in cerebellar tissue, that low dB rock music and noise created oxidative stress in the cortex and cerebellum, and that high and low dB slow music may have positive impacts on oxidative stress.

Synthesis of novel benzothiophene derivatives as protectors against cranial irradiation-induced neuroinflammation.

Aim: Cranial irradiation results in many deleterious effects to normal tissues, including neuroinflammation. There is a need to explore radioprotective agents that could be safely used to ameliorate these effects. Method: Nine novel benzothiophene derivatives bearing pyrimidinone, pyrazolidinone, triazole and other active moieties were synthesized andevaluated as antioxidants in an in vitro screening experiment. The most potent compounds were then tested as protectors against radiation-induced neuroinflammation and oxidative stress in rat brains following cranial irradiation. Results: The most potent antioxidant compounds were compounds 3-5 and 10 . P-fluro,p- bromo and pyrido benzothiophene derivatives offered good antioxidant and anti-inflammatory effects. Conclusion: Compounds 3-5 may be introduced as nontoxic candidates for adjuvant therapeutic protocols used in head and neck tumorradiotherapeutic management.

Protective effects of Vinca herbaceous extract against scopolamine-induced behavioral disturbances and brain oxidative stress in rats

Ethnopharmacological relevanceAlzheimer's disease (AD) as the most common type of dementia, is affecting the life of many senior individuals around the world. Vinca herbacea Waldst. & Kit. (V. herbacea) as a middle east originated plant demonstrated antioxidant and antitumor effects. This plant traditionally used to treat diabetes and hypertension, but its mechanism remains unclear. Aim of the studyIn the present study, post-treatment effects of V. herbacea on learning and memory functions, antioxidant cellular defense and oxidative stress were investigated using the scopolamine rat model of AD. Materials and methodsWistar male rats (170–190 g) were administered Scopolamine, an anti-muscarinic drug, (2 mg/kg) for 10 days followed by V. herbacea extract (200, 300 and 400 mg/kg) and/or donepezil (DON; 1 mg/kg, which were administered before behavioral studies for 10 consecutive days. All the rats were then subjected to Morris water maze (MWM) task. Biochemical parameters of oxidative stress were quantified using the whole brain. ResultsOur data showed significant decrease performance in target quadrant in water maze task following administration of scopolamine (SCOP). Also, V. herbacea and DON, did not induce any neurotoxicity and hepatotoxic effects at the highest utilized doses in healthy rats. Treatment with V. herbacea extract (200&400 mg/kg) and DON improved memory performance significantly in comparison with AD rats. In addition, V. herbacea extract in AD rats exhibited a decrease in malondialdehyde (MDA) and protein carbonyl (PCO) levels and an increase in total antioxidant capacity (FRAP) and glutathione (GSH) amounts in brain and liver. ConclusionIt seems that cholinergic deficits and oxidative stress are consistently associated with Alzheimer's disease (AD). The richness of V. herbacea in case of indole alkaloids and flavonoids confirms the potentials of this herb in management of oxidative stress, resorting synaptic acetylcholine level and improving cellular antioxidant resources.

Melatonin rescues cerebral ischemic events through upregulated tunneling nanotube-mediated mitochondrial transfer and downregulated mitochondrial oxidative stress in rat brain

BackgroundCerebral ischemic events, comprising of excitotoxicity, reactive oxygen production, and inflammation, adversely impact the metabolic-redox circuit in highly active neuronal metabolic profile which maintains energy-dependent brain activities. Therefore, we investigated neuro-regenerative potential of melatonin (Mel), a natural biomaterial secreted by pineal gland. MethodsWe specifically determined whether Mel could influence tunneling nanotubes (TNTs)-mediated transfer of functional mitochondria (Mito) which in turn may alter membrane potential, oxidative stress and apoptotic factors. In vitro studies assessed the effects of Mito on levels of cytochrome C, mitochondrial transfer, reactive oxygen species, membrane potential and mass, which were all further enhanced by Mel pre-treatment, whereas in vivo studies examined brain infarct area (BIA), neurological function, inflammation, brain edema and integrity of neurons and myelin sheath in control, ischemia stroke (IS), IS + Mito and IS + Mel-Mito group rats. ResultsResults showed that Mel pre-treatment significantly increased mitochondrial transfer and antioxidants, and inhibited apoptosis. Mel-pretreated Mito also significantly reduced BIA with improved neurological function. Apoptotic, oxidative-stress, autophagic, mitochondrial/DNA-damaged biomarkers indices were also improved. ConclusionConclusively, Mel is a potent biomaterial which could potentially impart neurogenesis through repairing impaired metabolic-redox circuit via enhanced TNT-mediated mitochondrial transfer, anti-oxidation, and anti-apoptotic activities in ischemia.

Activation of L-type calcium channels and attenuation of oxidative stress are involved in the improving effect of methyl jasmonate on learning and memory and its anxiolytic property in rats.

The present study was designed to evaluate the effect of plant bioactive compound methyl jasmonate on learning and memory, anxiety-like behaviors, and brain oxidative stress in rats. It has been indicated that methyl jasmonate stimulates calcium-binding protein expression and increases intracellular calcium (Ca2+). Therefore, we investigated the potential role of L-type calcium channel on methyl jasmonate effects. The animals were intracerebroventriculary (i.c.v.) injected with different doses of methyl jasmonate (0.5, 2.5, and 5 µg/rat). L-type calcium channel blocker (nifedipine 5 µg/rat, i.c.v.) was injected 30 min before methyl jasmonate (5 µg/rat). Shuttle box apparatus was used to evaluate passive avoidance memory. Anxiety-like behaviors were assessed by open field and elevated plus maze tests. Lastly, oxidative stress-related indices were assessed in hippocampus and prefrontal cortex. The data showed that methyl jasmonate dose-dependently could improve passive avoidance learning and memory and reduce anxiogenic behaviors. The methyl jasmonate effects were significantly prevented by nifedipine. Furthermore, central microinjection of methyl jasmonate significantly decreased hydrogen peroxide concentration, and increased reactive oxygen species scavenger activity (catalase and peroxide enzymes) in rats' hippocampus as well as prefrontal cortex. Indeed, the results indicated that the beneficial effects of methyl jasmonate on learning and memory and anxiety might be partly associated with L-type calcium channel and partly on the inhibition of oxidant indices.

Thymoquinone Improved Lead-Induced DNA Damage and Oxidative Stress in Rat Brain

Lead (Pb) is a pervasive industrial and environmental pollutant that seriously impairs the central nervous system, primarily by disrupting the redox balance. The current research was conducted to explore the possible beneficial action of thymoquinone (TQ), the main active component in Nigella sativa seed volatile oil, against brain oxidative stress and DNA damage caused by Pb. Wistar adult male rats were treated with TQ (5 mg/kg/day, per os) and/or Pb (2000 ppm of Pb acetate in drinking water) for five weeks. Results showed that Pb exposure significantly increased metal content, malondialdehyde concentration and DNA damage (assessed by comet assay), but significantly decreased the level of reduced glutathione and the activities of catalase, glutathione peroxidase, and superoxide dismutase in the brain tissue. These detrimental effects Pb-induced, except tissue metal accumulation, were significantly improved by TQ supplementation. In conclusion, our findings suggested that TQ might be a promising therapeutic alternative in Pb neurotoxicity.

Artificial sweeteners elicit oxidative stress in rat brain and development of microcytic anemia: Promising protective effects of vitamin C

Artificial sweeteners elicit oxidative stress in rat brain and development of microcytic anemia: Promising protective effects of vitamin C

Enhanced anti-amnestic effect of donepezil by Ginkgo biloba extract (EGb 761) via further improvement in pro-cholinergic and antioxidative activities

Ethnopharmacological relevanceEGb 761 is a standardized dry extract of Ginkgo biloba L. leaves traditionally used by Eastern Asia and has been associated with beneficial effects on neurodegeneration disorders, including Alzheimer's disease. Aim of the studySince beneficial interactions between EGb 761 and donepezil have been observed in previous clinical studies, the current study was proposed aiming to further explore related mechanisms from both pharmacokinetics and pharmacodynamics aspects. Materials and methodsPharmacodynamic interactions were studied in scopolamine-induced cognitive impairment rats received two-weeks treatment of vehicle, EGb 761 and/or donepezil by the Morris water maze test and ex vivo evaluation of biomarkers of cholinergic transmission and oxidative stress in rat brain. In the meantime, pharmacokinetic profiles of donepezil and bilobalide were obtained and compared among all treatment groups. In addition, impact of the bioavailable EGb 761 components on donepezil brain penetration was evaluated with the hCMEC/D3 cell monolayer model. ResultsScopolamine-induced rats with co-treatment of EGb 761 and donepezil had significantly improved cognitive function in the Morris water maze test with increased brain levels of superoxide dismutase and decreased brain levels of acetylcholinesterase and malondialdehyde than that with treatment of only EGb 761 or donepezil. Despite such beneficial pharmacodynamics outcomes, the two-week co-treatment of EGb 761 and donepezil did not alter the plasma pharmacokinetics and brain uptake of donepezil or bilobalide, which was further verified in the hCMEC/D3 monolayer model. ConclusionCo-administration of EGb 761 and donepezil exerted better anti-amnestic effect via further enhanced pro-cholinergic and antioxidative effects of EGb 761 or donepezil in scopolamine-induced cognitive impairment rat without alteration in their systemic/brain exposure.

Astrocyte-derived exosomes carry microRNA-17-5p to protect neonatal rats from hypoxic-ischemic brain damage via inhibiting BNIP-2 expression

Exosomes play critical roles in neurogenesis. This study aims to explore the mechanism of astrocyte-derived exosomes in neonatal rats with hypoxic-ischemic brain damage (HIBD). Astrocytes were collected and astrocyte-derived exosomes were isolated and identified. Neonatal rats were pre-treated with exosomes and then subjected to HIBD induction. Then the neurobehaviors, neuronal apoptosis, inflammation and oxidative stress in rat brain were measured. Differentially expressed microRNAs (miRNAs) in rat brain before and after HI procedure were analyzed. H19-7 cells were subjected to oxygen and glucose deprivation (OGD) for in vitro studies. Target relation between miR-17-5p and BNIP2 was identified. Gain- and loss-of functions of miR-17-5p and BNIP2 were conducted to identify their roles in viability, apoptosis, oxidative stress and inflammation of OGD-treated cells. Collectively, astrocyte-derived exosomes improved neurobehaviors, and reduced cerebral infarction, neuronal apoptosis, oxidative and inflammation in vivo and in vitro. The exosomes carried miR-17-5p bound to BNIP2 and negatively regulated BNIP2 expression in OGD-treated cells. Over-expression of miR-17-5p increased viability, and decreased OGD-induced apoptosis, oxidative stress and inflammation of H19-7 cells, which were reversed by over-expression of BNIP2. Taken together, the study suggested that astrocyte-derived exosomes could carry miR-17-5p to protect neonatal rats from HIBD via inhibiting BNIP-2 expression.

Glycine nano-selenium prevents brain oxidative stress and neurobehavioral abnormalities caused by MPTP in rats

BackgroundParkinson's disease (PD) is a common degenerative disease of the central nervous system in the elderly. In recent years, the results of clinical and experimental studies have shown that oxidative stress is one of the important pathogenesis of PD. Selenium is one of the minor elements reported to possess antioxidant properties. Thus, the purpose of this study was to investigate the recovery effect of glycine nano-selenium on neurobehavioral abnormalities and oxidative stress caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in rat. Materials and methodsSD male rats weighing 280−310 g were purchased from the Chengdu Dossy Experimental Animals Company, China. All rats were housed in a temperature-controlled room, with a 12 h light–dark cycles and had free access to food and water ad libitum. Rats were randomly divided into 4 groups with 8 animals in each group: the control group (normal saline), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine group (MPTP), MPTP + 0.05 mg/kg glycine nano-selenium (MPTP + 0.05 Se), MPTP + 0.1 mg/kg glycine nano-selenium (MPTP + 0.1 Se). Behavioral assessment, clinical symptoms, Immunohistochemistry analysis of tyrosine hydroxylase (TH) and antioxidant activity were accessed to determine the protective effects glycine nano-selenium have on PD rats. ResultsFrom the results, Rats showed a decrease in spontaneous motor behavior and an increase in pole test score. Also, the number of TH+ neurons were also significantly decreased (P < 0.05) after treated with MPTP for 7 days indicating that MPTP could successfully induce neurobehavioral abnormalities in rats. Furthermore, the lipid peroxide (MDA) levels of the PD model group were significantly increased and the antioxidant activities (SOD and GSH-PX) were significantly inhibited (P < 0.05) compared to the control group indicating the important role oxidative stress played in dopaminergic neuron death and neurobehavioral abnormalities in PD rats. Compared with the PD model group, glycine nano-selenium administration could significantly improve behavior and increase the number of TH+ neurons (P < 0.05) to protect against the loss of dopaminergic neurons. At the same time, glycine nano-selenium could decrease the MDA levels and increase the activities of SOD and GSH-PX significantly (P < 0.05). ConclusionIn conclusion, PD rat model was successfully developed by intraperitoneal injection of MPTP and the intragastric administration of glycine nano-selenium reduced neurobehavioral abnormalities by decreasing oxidative stress in rat brain.

Supplementation of Taurine Insulates Against Oxidative Stress, Confers Neuroprotection and Attenuates Memory Impairment in Noise Stress Exposed Male Wistar Rats.

Noise has always been an important environmental factor that induces health problems in the general population. Due to ever increasing noise pollution, humans are facing multiple auditory and non-auditory problems including neuropsychiatric disorders. In modern day life it is impossible to avoid noise due to the rapid industrialization of society. Continuous exposure to noise stress creates a disturbance in brain function which may lead to memory disorder. Therefore, it is necessary to find preventive measures to reduce the deleterious effects of noise exposure. Supplementation of taurine, a semi essential amino acid, is reported to alleviate psychiatric disorders. In this study noise-exposed (100 db; 3h daily for 15days) rats were supplemented with taurine at a dose of 100mg/kg for 15days. Spatial and recognition memory was assessed using the Morris water maze and novel object recognition task, respectively. Results of this study showed a reversal of noise-induced memory impairment in rats. The derangements of catecholaminergic and serotonergic levels in the hippocampus and altered brain antioxidant enzyme activity due to noise exposure were also restored by taurine administration. This study highlights the importance of taurine supplementation to mitigate noise-induced impaired memory via normalizing the neurochemical functions and reducing oxidative stress in rat brain.

Acute emotional stress and high fat/high fructose diet modulate brain oxidative damage through NrF2 and uric acid in rats

Studies focusing on the interaction of dietary and acute emotional stress on oxidative stress in cortex frontal and in brain mitochondria are scarce. Dietary-induced insulin resistance, as observed in Western diets, has been associated with increased oxidative stress causing mitochondrial dysfunction. We hypothesized that acute emotional stress could be an aggravating factor by impacting redox status in cortex and brain mitochondria. Thus, the aim of the present study was to evaluate the combination of an insulin resistance inducing high-fat/high-fructose (HF/HFr) diet and acute emotional stress on brain oxidative stress in rats. We measured several oxidative stress parameters (carbonyls, FRAP, TBARS assays, GSH, GSSG, oxidized DNA, mRNA expression of redox proteins (Nrf2), and uric acid). The HF/HFr diet resulted in increased oxidative stress both in the brain mitochondria and in the frontal cortex and decreased expression of the Nrf2 gene. The emotional stress induced an oxidative response in plasma and in brain mitochondria of the control group. In the HF/HFr group it triggered an increase expression of the redox transcription factor Nrf2 and its downstream antioxidant genes. This suggests an improvement of the redox stress tolerance in response to an enhanced production of reactive oxygen species. Accordingly, a blunted oxidative effect on several markers was observed in plasma and brain of HF/HFr-stressed group. This was confirmed in a parallel study using lipopolysaccharide as a stress model. Beside the Nrf2 increase, the stress induced a stronger UA release in HF/HFr which could take a part in the redox stress.

Oral ascorbic acid 2-glucoside prevents coordination disorder induced via laser-induced shock waves in rat brain.

Oxidative stress is considered to be involved in the pathogenesis of primary blast-related traumatic brain injury (bTBI). We evaluated the effects of ascorbic acid 2-glucoside (AA2G), a well-known antioxidant, to control oxidative stress in rat brain exposed to laser-induced shock waves (LISWs). The design consisted of a controlled animal study using male 10-week-old Sprague-Dawley rats. The study was conducted at the University research laboratory. Low-impulse (54 Pa•s) LISWs were transcranially applied to rat brain. Rats were randomized to control group (anesthesia and head shaving, n = 10), LISW group (anesthesia, head shaving and LISW application, n = 10) or LISW + post AA2G group (AA2G administration after LISW application, n = 10) in the first study. In another study, rats were randomized to control group (n = 10), LISW group (n = 10) or LISW + pre and post AA2G group (AA2G administration before and after LISW application, n = 10). The measured outcomes were as follows: (i) motor function assessed by accelerating rotarod test; (ii) levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative stress marker; (iii) ascorbic acid in each group of rats. Ascorbic acid levels were significantly decreased and 8-OHdG levels were significantly increased in the cerebellum of the LISW group. Motor coordination disorder was also observed in the group. Prophylactic AA2G administration significantly increased the ascorbic acid levels, reduced oxidative stress and mitigated the motor dysfunction. In contrast, the effects of therapeutic AA2G administration alone were limited. The results suggest that the prophylactic administration of ascorbic acid can reduce shock wave-related oxidative stress and prevented motor dysfunction in rats.

Effects of Bisphenol A on Oxidative Stress in the Rat Brain.

We investigated the effect of bisphenol A (BPA) on oxidative stress and tau-related proteins in adult rat brains. BPA (10 mg/L) was administered to rats for eight weeks through their drinking water. The reactive oxygen species (ROS) scavenging capacity for hydroxyl radicals in the plasma was reduced after two weeks. In the hippocampus, four and eight weeks of BPA increased the ratio of oxidized DJ-1/DJ-1 (PARK7). The ratio of phosphorylated-GSK3β/GSK3β and phosphorylated-AKT/AKT increased after one week of BPA treatment. The ratio of phosphorylated JNK/JNK and phosphorylated-ERK/ERK increased after eight weeks of BPA; the elevation could be related to tau phosphorylation. Protein phosphatase 2A (PP2A) in the hippocampus decreased after eight weeks of BPA treatment. At that time, SOD1 was significantly induced, but no changes in SOD2 expression were apparent in the hippocampus. Furthermore, the ratio of phosphorylated-tau (PHF-1, Ser396/ Ser404) to total tau level did not change. However, PHF-1 or other sites of tau could be phosphorylated after eight weeks in the hippocampi of rats. BPA induced systemic oxidative stress and could change ROS-induced signaling pathways in the brain. These results suggest that mitochondrial dysfunction possibly is not responsible for oxidative stress and neurodegeneration due to low doses of BPA.