Superoxide Dismutase Activity In Brain Research Articles

Omics techniques reveal the toxicity mechanisms of three antiepileptic drugs to juvenile zebrafish (Danio rerio) brain and liver

Epilepsy, a neurological disorder, is characterized by seizures that are an appearance of excessive brain activity and is symptomatically treated with antiepileptic drugs (AEDs). Oxcarbazepine (OCBZ), lamotrigine (LTG), and carbamazepine (CBZ) are widely used AEDs in clinics and are very often detected in aquatic environments. However, neither the sub-lethal effects nor the specific mechanisms of these AEDs’ action on the fish are well understood. In this study, juvenile zebrafish were exposed to a sub-lethal concentration (100 μg/L) of OCBZ, LTG, and CBZ for 28 d, after which indicators of oxidative stress (i.e. superoxide dismutase (SOD) activity, catalase (CAT) activity, and malondialdehyde (MDA) level) and neurotoxicity (i.e. acetylcholinesterase (AChE) activity, γ-aminobutyric acid (GABA) level, and glutamic acid (Glu) level) were measured. Brain SOD activity was significantly increased by three AEDs, while brain CAT activity was significantly inhibited by LTG and CBZ. Liver SOD activity was significantly enhanced by CBZ, and liver CAT activity was significantly induced by OCBZ and LTG. Liver MDA level was significantly increased by three AEDs. Brain AChE activity was significantly increased by LTG and CBZ, and brain GABA level was significantly enhanced by three AEDs. However, there were no significant alterations in the levels of MDA and Glu in zebrafish brain. To ascertain mechanisms of AEDs-induced toxicity, brain transcriptomics and liver metabolomics were conducted in zebrafish. The brain transcriptomics results showed that lots of differentially expressed genes (DEGs) were enriched in the sensory system, the immune system, the digestive system, the metabolic processes, and others in three AEDs treated groups. The metabolomics data indicated dysregulation of glycerophospholipid signaling and lipid homeostasis in zebrafish liver after three AEDs exposure. The overall results of this study improve understanding of the sub-lethal effects and potential molecular mechanisms of action of AEDs in fish.

Beneficial effects of sennoside B on pentylenetetrazole-induced seizures in rats.

Epilepsy is a common disorder affecting approximately 50 million people worldwide. Oxidative stress is known to play an important role in the pathophysiology of diseases, including epilepsy. In this study, we investigated the effects of sennoside B on PTZ-induced seizures in rats. The rats were grouped into Group Electroencephalography and Group Behavioral. Both Groups were divided into eight subgroups, and these subgroups were compared in terms of the time of first myoclonic jerk, Racine's Convulsion Scale, malondialdehyde levels, and brain superoxide dismutase activity. The experimental seizure model was performed with pentylenetetrazol. The spike percentage was significantly lower in groups that received sennoside B, and this beneficial effect was shown to be associated with the dose of sennoside B received. The RCS score was lower and the FJM onset time was higher in the sennoside B-administered groups. Additionally, brain MDA and brain aquaporin-3 levels were lower and brain SOD activity was higher in the sennoside-administered groups. The present study shows the beneficial effects of sennoside B on PTZ-induced convulsion in rats. It is considered that sennoside B which is a natural and safe product would be a good candidate for strengthening the management of epilepsy without serious side effects.

Biochemical regulatory processes in the control of oxidants and antioxidants production in the brain of rats with iron and copper chronic overloads.

Iron [Fe(II)] and copper [Cu(II)] overloads in rat brain are associated with oxidative stress and damage. The purpose of this research is to study whether brain antioxidant enzymes are involved in the control of intracellular redox homeostasis in the brain of rats male Sprague-Dawley rats (80-90g) that received drinking water supplemented with either 1.0g/L of ferrous chloride (n = 24) or 0.5g/L cupric sulfate (n = 24) for 42days. Nicotinamide adenine dinucleotide phosphate(NADPH) oxidase, superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione transferase (GT) activities in brain were determined by spectrophotometric methods and NO production by the content of nitrite concentration in the organ. Chronic treatment with Fe(II) and Cu(II) led to a significant decrease of nitrite content and SOD activity in brain. Activity of NADPH oxidase increased with Cu(II) treatment. Concerning Fe(II), catalase and GT activities increased in brain after 28 and 4days of treatment, respectively. In the case of Cu(II), catalase activity decreased whereas GT activity increased after 2 and 14days, respectively. The regulation of redox homeostasis in brain involves changes of the activity of these enzymes to control the steady state of oxidant species related to redox signaling pathways upon Cu and Fe overload. NO may serve to detoxify cells from superoxide anion and hydrogen peroxide with the concomitant formation of peroxynitrite. However, the latest is a powerful oxidant which leads to oxidative modifications of biomolecules. These results suggest a common pathway to oxidative stress and damage in brain for Cu(II) and Fe(II).

Nanostructure lipid carriers enhance alpha-mangostin neuroprotective efficacy in mice with rotenone-induced neurodegeneration.

Neurodegenerative disease, for instance, Parkinson's disease (PD), is associated with substantia nigra dopaminergic neuronal loss with subsequent striatal dopamine reduction, leading to motor deficits. Currently, there is no available effective therapy for PD; thus, novel therapeutic agents such as natural antioxidants with neuroprotective effects are emerging. Alpha-mangostin (αM) is a xanthone derivative compound from mangosteen peel with a cytoprotective effect depicted in neurodegenerative disease models. However, αM has low aqueous solubility and low biodistribution in the brain. Nanostructured lipid carriers (NLC) have been used to encapsulate bioactive compounds delivered to target organs to improve the oral bioavailability and effectiveness. This study aimed to investigate the effect of αM and αM encapsulated in NLC (αM-NLC) in mice with rotenone-induced PD-like neurodegeneration. Forty male ICR mice were divided into normal, PD, PD + αM, and PD + αM-NLC groups. Vehicle, αM (25mg/kg/48h), and αM-NLC (25mg/kg/48h) were orally administered, along with PD induction by intraperitoneal injection of rotenone (2.5mg/kg/48h) for 4 consecutive weeks. Motor abilities were assessed once a week using rotarod and hanging wire tests. Biochemical analysis of brain oxidative status was conducted, and neuronal populations in substantia nigra par compacta (SNc), striatum, and motor cortex were evaluated using Nissl staining. Tyrosine hydroxylase (TH) immunostaining of SNc and striatum was also evaluated. Results showed that rotenone significantly induced motor deficits concurrent with significant SNc, striatum, and motor cortex neuronal reduction and significantly decreased TH intensity in SNc (p < 0.05). The significant reduction of brain superoxide dismutase activity (p < 0.05) was also detected. Administrations of αM and αM-NLC significantly reduced motor deficits, prevented the reduction of TH intensity in SNc and striatum, and prevented the reduction of neurons in SNc (p < 0.05). Only αM-NLC significantly prevented the reduction of neurons in both striatum and motor cortex (p < 0.05). These were found concurrent with significantly reduced malondialdehyde level and increased catalase and superoxide dismutase activities (p < 0.05). Therefore, this study depicted the neuroprotective effect of αM and αM-NLC against rotenone-induced PD-like neurodegeneration in mice. We indicated an involvement of NLC, emphasizing the protective effect of αM against oxidative stress. Moreover, αM-NLC exhibited broad protection against rotenone-induced neurodegeneration that was not limited to nigrostriatal structures and emphasized the benefit of NLC in enhancing αM neuroprotective effects.

Comparison of Effects of High-Intensity Interval Training and Continuous Training on Memory and Correlation with Antioxidant Enzyme Activity in the Rat Brain

Objectives: This study aimed to investigate the effects of six-week continuous training (CT) and high-intensity interval training (HIIT) protocols on brain superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities and their associations with short-, mid-, and long-term memory in albino Wistar rats. Methods: In this study, 18 male albino Wistar rats (5 months old) were randomly assigned to three equal (n = 6) groups of sedentary control (SC), CT, and HIIT. Both CT and HIIT regimens were performed for 6 consecutive days per week for 6 weeks. Results: Both HIIT and CT regimens increased short-, mid-, and long-term memory, and the alterations were greater following HIIT than CT. In addition, both HIIT and CT regimens significantly increased SOD activity, with a higher elevation following HIIT than CT. Moreover, brain SOD activity positively correlated with short-, mid-, and long-term memory. However, neither CT nor HIIT had a significant effect on brain GPX and CAT activities. Conclusions: The HIIT regimen is highly potential, as opposed to the CT regimen, to improve memory function through a greater increase in the SOD activity of the brain.

Behavioral effects of zinc oxide nanoparticles on the brain of rats

Recent studies showed that zinc oxide nanoparticles (ZnO-NPs) can cause toxic damage to the central nervous system (CNS) after intraperitoneal injection; however, the behavioral effects of ZnO-NPs have not been fully investigated. This study aimed to resolve these discrepancies by examining the effects of poly(ethylene glycol)-based on the ZnO-NPs on antioxidant status in healthy rats. The structural, morphology and size characterization of nanoparticles were studied by applying techniques like XRD and TEM. Intraperitoneal injection of ZnO-NPs at a concentration of 25 mg/kg /day had no significant effect on the brain catalase (CAT), superoxide dismutase (SOD), and reduced glutathione content (GSH). Treatment with the 100 mg/kg dose of ZnO nanoparticles significantly increased brain MDA (P < 0.01), and significantly decreased brain catalase activity (P < 0.05), and brain superoxide dismutase activity (P < 0.05) compared to the control group. The high doses of ZnO-NPs caused prominent changes to brain histology. The results suggest that ZnO-NPs could induce behavioral changes and brain histological changes.

Effects of transcranial photobiomodulation and methylene blue on biochemical and behavioral profiles in mice stress model

The effectiveness of transcranial photobiomodulation (tPBM) and methylene Blue (MB) in treating learning and memory impairments is previously reported. In this study, we investigated the effect of tPBM and MB in combination or alone on unpredictable chronic mild stress (UCMS)–induced learning and memory impairments in mice. Fifty-five male BALB/c mice were randomly allocated to five groups: control, laser sham + normal saline (NS), tPBM + NS, laser sham + MB, and tPBM + MB. All groups except the control underwent UCMS and were treated simultaneously for 4 weeks. Elevated plus maze (EPM) was used to evaluate anxiety-like behaviors. Novel object recognition (NOR) test and Barnes maze tests were used to evaluate learning and memory function. The serum cortisol and brain nitric oxide (NO), reactive oxygen species (ROS), total antioxidant capacity (TAC), glutathione peroxidase (GPx), and superoxide dismutase (SOD) levels were measured by spectrophotometric methods. Behavioral tests revealed that UCMS impaired learning and memory, and treatment with PBM, MB, and their combination reversed these impairments. Levels of NO, ROS, SOD activity in brain, and serum cortisol levels significantly increased while brain GPx activity and total antioxidant capacity significantly decreased in the sham + NS animals when compared with the controls. A significant improvement was observed in treatment groups due to reversion of the aforementioned molecular analysis caused by UCMS when it was compared with control levels. Both tPBM and MB in combination or alone have significant therapeutic effects on learning and memory impairments in UCMS-received animals.

Antioxidant Effects of Pomegranate Seed Oil Against Pentachlorophenol Toxicity in Rat Tissues

This study was conducted to evaluate the effects of pomegranate seed oil PSO on the oxidative stress induced by pentachlorophenol PCP in rats. Fourty Sprague-Dawley, 4-5 months old, 300g male rats were used in this study. Rats were assigned to four groups each containing 10 animals. First group was control group; no administration was made to animals in this group. Second, third and fourth groups were given PSO at a dose of 0.15 ml/kg bw, PCP at a dose of 40 mg/kg bw and PSO at a dose of 0.15 ml/kg bw+PCP at a dose of 40 mg/kg bw orally by gavage for 28 days, respectively. At the end of the study, brain, liver, kidney, testicle and spleen samples were collected. Malondialdehyde (MDA) level and catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were measured in tissue samples. PCP caused an increase of MDA level in brain, kidney, liver and testicle; a decrease of CAT activity in liver and spleen; a decrease of GSH-Px activity in brain and testicle and a decrease of SOD activity in brain, liver and kidney compared to control group. When PSO+PCP group compared to PCP group, MDA level decreased in brain, liver and testicle; CAT activity increased in spleen; SOD activity increased in brain and kidney. When compared to the control group and the group given PSO+PCP, the data of PSO+PCP group were generally similar to the control group. As a result, administration of PCP at the dose of 40 mg/kg bw for 28 days caused oxidative stress and administration of PSO at the dose of 0.15 ml/kg bw alleviated severity of PCP induced oxidative stress

An effort toward molecular biology of food deprivation induced food hoarding in gonadectomized NMRI mouse model: focus on neural oxidative status

BackgroundEnvironmental uncertainty, such as food deprivation, may alter internal milieu of nervous system through various mechanisms. In combination with circumstances of stress or aging, high consumption of unsaturated fatty acids and oxygen can make neural tissues sensitive to oxidative stress (OS). For adult rats, diminished level of gonadal steroid hormones accelerates OS and may result in special behavioral manifestations. This study was aimed to partially answer the question whether OS mediates trade-off between food hoarding and food intake (fat hoarding) in environmental uncertainty (e.g., fluctuations in food resource) within gonadectomized mouse model in the presence of food deprivation-induced food hoarding behavior.ResultsHoarding behavior was not uniformly expressed in all male mice that exposed to food deprivation. Extended phenotypes including hoarder and non-hoarder mice stored higher and lower amounts of food respectively as compared to that of low-hoarder mice (normal phenotype) after food deprivation. Results showed that neural oxidative status was not changed in the presence of hoarding behavior in gonadectomized mice regardless of tissue type, however, glutathione levels of brain tissues were increased in the presence of hoarding behavior. Decreased superoxide dismutase activity in brain and spinal cord tissues and increased malondialdehyde in brain tissues of gonadectomized mice were also seen.ConclusionsAlthough, food deprivation-induced hoarding behavior is a strategic response to food shortage in mice, it did not induce the same amount of hoarding across all colony mates. Hoarding behavior, in this case, is a response to the environmental uncertainty of food shortage, therefore is not an abnormal behavior. Hoarding behavior induced neural OS with regard to an increase in brain glutathione levels but failed to show other markers of neural OS. Decreased superoxide dismutase activity in brain and spinal cord tissues and increased malondialdehyde levels in brain tissues of gonadectomized mice could be a hallmark of debilitated antioxidative defense and more lipid peroxidation due to reduced amount of gonadal steroid hormones during aging.

Effects of increasing temperature on antioxidant defense system and oxidative stress parameters in the Antarctic fish Notothenia coriiceps and Notothenia rossii

Antioxidant defense system (ADS) and oxidative stress parameters were evaluated in the Antarctic fish Notothenia rossii and N. coriiceps exposed to increasing temperature. Acclimated fish were kept at 0°C or exposed to 4°C for 1day (N. rossii) or to 2 and 4°C for 1 and 6 days (N. coriiceps). Measurements were assessed in brain, gills, liver, white muscle and erythrocytes. Parameters analyzed included antioxidant capacity against peroxyl radicals (ACAP); reduced glutathione (GSH) and metallothionein-like proteins (MTLP) concentration; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutamate-cysteine ligase (GCL) activity; lipid peroxidation (LPO) level and protein carbonyl (PC) concentration. Increased liver GST activity was observed in N. rossii exposed to 4°C for 1day. Increased muscle GPx activity was observed in N. coriiceps after exposure to 2°C for 1day. Reduced gill GPx activity and increased liver SOD activity were observed after exposure to 4°C for 1day. In N. coriiceps, increased gill GCL activity and reduced gill GPx activity, as well as reduced liver MTLP were observed after exposure to 2°C for 6 days. Reduced brain SOD activity and increased brain LPO; reduced gill ACAP, GSH concentration and GPx activity, as well as increased gill GCL activity; reduced liver ACAP, MTLP, SOD activity, GST activity and increased liver and erythrocytes LPO were observed after exposure to 4°C for 6 days. These findings indicate that ADS is more responsive to short-term increasing temperature in the sluggish N. coriiceps than in the active N. rossii. However, responses of N. coriiceps to long-term increasing temperature were transient and did not prevent tissue oxidative damage. Considering the predicted increase in temperature in the Southern Ocean over the next decades, our findings suggest that Antarctic fishes are sensitive to ocean warming, displaying tissue oxidative damage associated with the thermal stress.

Neurotoxic effects of nickel chloride in the rainbow trout brain: Assessment of c-Fos activity, antioxidant responses, acetylcholinesterase activity, and histopathological changes

The aim of this study was to determine the biochemical, immunohistochemical, and histopathological effects of nickel chloride (Ni) in the rainbow trout brain. Fish were exposed to Ni concentrations (1mg/L and 2mg/L) for 21days. At the end of the experimental period, brain tissues were taken from all fish for c-Fos activity and histopathological examination and determination of acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CAT) enzyme activities, lipid peroxidation (LPO), and glutathione (GSH) levels. Our results showed that Ni treatment caused a significant increase in the brain SOD activity and in LPO and GSH levels (p<0.05), but it significantly decreased AChE and CAT enzyme activities (p<0.05). Strong induction in c-Fos was observed in some cerebral and cerebellar regions of fish exposed to Ni concentrations when compared with the control group. However, c-Fos activity was decreased in necrotic Purkinje cells. Brain tissues were characterized by demyelination and necrotic changes. These results suggested that Ni treatment causes oxidative stress, changes in c-Fos activity, and histopathological damage in the fish brain.

The Novel Tetramethylpyrazine Bis-nitrone (TN-2) Protects Against MPTP/MPP+-Induced Neurotoxicity via Inhibition of Mitochondrial-Dependent Apoptosis

Mitochondrial-dependent apoptosis plays an important role in the degeneration of dopaminergic neurons in Parkinson's disease (PD). Methyl-4-phenyl-1,2,3,6-tetra- hydropyridine (MPTP), the most widely used neurotoxin to simulate PD, is converted to 1-methyl-4-phenylpyridinium (MPP(+)) in vivo. MPP(+) induces excessive intracellular reactive oxygen species (ROS), leading to mitochondrial-dependent apoptosis via sequentially opening mitochondria permeability transition pore (mPTP) to release cytochrome c from mitochondria into cytoplasm and activate pro-apoptotic caspase proteins. We have previously synthesized 2,5-[[(1,1-dimethylethyl)oxidoimino]methyl]-3,6-trimethylpyrazine (TN-2), a novel derivative of the Chinese herb medicine tetramethylpyrazine (TMP). TN-2 is armed with two powerful free radical-scavenging nitrone moieties. TN-2 significantly reversed the loss of dopaminergic neurons in the substantia nigra and the decrease in dopamine level in the striatum induced by MPTP in mice. TN-2 ameliorated the MPTP-induced decrease of brain superoxide dismutase activity and glutathione concentration and increase of brain malondialdehyde. In addition, TN-2 inhibited MPP(+)-induced neuronal damage/apoptosis in primary cerebellum granular neurons (CGNs) and SH-SY5Y cells. TN-2 decreased excessive intracellular ROS, prevented the loss of mitochondrial membrane potential, blocked the release of mitochondrial cytochrome c and inhibited the activation of caspase-3 and caspase-9. Moreover, TN-2 treatment increased the mRNA expression of mitochondrial biogenesis factors peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1 (PGC- 1α and β) and mitochondrial transcription factor A (Tfam) in SH-SY5Y cells and CGNs. These results suggest that TN-2 protects dopaminergic neurons against MPTP/MPP(+)-induced neurotoxicity via the inhibition of mitochondrial-dependent apoptosis and possibly via the activation of mitochondrial biogenesis, indicating that TN-2 is a potential new treatment for PD.

Effect of chronic exposure to prometryne on oxidative stress and antioxidant response in common carp (Cyprinus carpio L.)

The effects of the triazine herbicide prometryne, commonly present in surface and ground waters, on oxidative stress and antioxidant status of common carp (Cyprinus carpio) were investigated. Fish were exposed to sublethal concentrations of prometryne (0.51, 8, and 80μg/l) for 14, 30, and 60days. Activity of superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR), as well as levels of thiobarbituric acid reactive substances (TBARSs) were assessed in brain, gill, intestine, liver, and muscle. After 14days exposure, decreased GR activity in brain was observed for all prometryne-exposed groups compared with the controls. Changes were observed in SOD activity in brain and gill after 30days in all exposure groups. Changes in CAT activity were observed only at the highest concentration (80μg/l) in liver and intestine after 60days. The observed effects on carp antioxidant systems may be a defense against oxidative damage. The study demonstrated changes in antioxidant parameters and the importance of evaluating the potential long-term risk to fish of prometryne, at environmentally realistic concentrations (0.51μg/l). The results suggest that antioxidant responses may have potential as biomarkers for monitoring residual triazine herbicides in aquatic environments.

Study on Modified Shengmai Yin Injection for Prevention and Treatment of Brain Impairment in Endotoxin Shock Rats

To examine the effects of modified Shenmai Yin on invigorating vital energy, promoting blood flow, and protection against neural impairment in an endotoxin-induced shock rat model. Ninety-six SD rats were randomly divided into four groups: sham operation (saline 20 ml/kg), shock model (lipopolysaccharide, LPS, 8 mg/kg), Reformed Shengmai Yin (Pulse-activating Decoction) (LPS 8 mg/kg + reformed Shengmai Yin Injection 10 ml/kg), and dexamethasone (LPS 8 mg/kg + dexamethasone 5 mg/kg) groups. Each group was subdivided into 1 h, 2 h, 3 h, and 6 h time points for observation. The carotid artery was separated and connected with a biological functional system to monitor mean arterial pressure (MAP). Brain water levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity were also determined. In the shock model group, MAP was progressively decreased after injection of LPS, brain water and MDA contents were increased, brain SOD activity was decreased, and capillary vessel edema in brain tissue was also observed. All these parameters were improved significantly in both treatment groups, although the effects were more marked with Shengmai Yin than with dexamethasone. Modified Shengmai Yin exhibits strong anti-shock and neuroprotective effects against Endotoxin-induced shock.

Salt and Nitric Oxide Synthase Inhibition-Induced Hypertension: Kidney Dysfunction and Brain Anti-Oxidant Capacity

The specific aim of this study was to examine the effects of salt-loading on kidney function and brain antioxidant capacity. Wistar rats were divided into four groups: Control rats were given normal drinking water and no drug treatment for 2 weeks. LNNA group: rats were given normal drinking water and the nitric oxide (NO) inhibitor NG-nitro-L-arginine (L-NNA), 3 mg/kg/day. LNNA + Salt group: rats were given drinking water containing salt 2% and 3 mg/kg L-NNA. Salt group: rats were given drinking water containing salt 2% and no drug treatment. Basal blood pressure and the levels of serum BUN, creatinine, uric acid, cortisol, electrolyte, serum antioxidant capacity, and oxidative stress were measured. NO, superoxide dismutase (SOD), and catalase (CAT) levels were measured in the hypothalamus, brainstem, and cerebellum. Salt overload increased the blood pressure of the LNNA + Salt group. Salt-loading enhanced BUN, creatinine, sodium retention. High salt produced an increase in uric acid levels and a decrease in cortisol levels in serum. Additionally, the oxidative stress index in serum increased in the LNNA + Salt group. Salt-loading enhanced brain NO levels, but not SOD and CAT activity. L-NNA increased brain SOD activity, but not CAT and NO levels. In conclusion, salt-loading causes hypertension, kidney dysfunction, and enhances oxidative stress in salt-sensitive rats.

Chromium effects on free radical processes in goldfish tissues: Comparison of Cr(III) and Cr(VI) exposures on oxidative stress markers, glutathione status and antioxidant enzymes

The present study directly compared the effects of exposure to Cr 6+ and Cr 3+ (10 mg/L) over 24, 48 and 96 h on indices of oxidative stress and activities of antioxidant and related enzymes in goldfish brain, liver, kidney and gills. Glutathione status clearly demonstrated the development of oxidative stress, whereas changes in protein carbonyls and lipid peroxides were less pronounced. The activity of superoxide dismutase (SOD) was virtually unaffected after 24 or 96 h exposure, but 48 h exposure to Cr 6+ reduced SOD activity in brain (by 30%), enhanced activity in kidney (by 28%) and had no effect on liver SOD. Chromium exposure for shorter times had no effect on catalase activity, whereas 96 h exposure depressed activity in liver, kidney and gills. Exposure to Cr 6+ reduced catalase activity in liver by 53% and in kidney by 21%, while in gills it was reduced by 20 and 38% by exposure to Cr 3+ and Cr 6+, respectively. Exposure to chromium for 24 h did not affect glutathione-S-transferase activity, but treatment with Cr 6+ for 48 h enhanced it in brain by 1.5-fold, whereas exposure to Cr 3+ decreased activity by 29% in kidney. Fish treatment with chromium ions for 96 h decreased glutathione-S-transferase activity in liver by 51 and 25%, respectively. Chromium exposure had very little effect on the activities of GR or G6PDH. These data show that both chromium ions induced oxidative stress in goldfish tissues and affected the activity of antioxidant and associated enzymes.

Protective role of dark soy sauce against acrylamide-induced neurotoxicity in rats by antioxidative activity

Dark soy sauce (DSS) exerts antioxidant activity in vitro or in vivo. To test the possibility of chemoprevention by such dietary supplements on acrylamide (ACR)-induced subacute toxicity, Sprague-Dawley male rats were administered DSS dissolved in water (0.5 ml/kgbw•d) for 2 weeks after, before or during ACR exposure (0.2 mg/L in distillate water). DSS significantly improved the body weight gain, relative brain weights, and the gait abnormalities of ACR-treated rats when DSS treated at the same time as ACR-exposure (p < 0.05). DSS significantly improved the axonal degeneration, the ratio of myelinated nerves < 3 μm in diameter, degree of central chromatolysis of the ganglion neurons in peripheral nerves, and numbers of SYP (+) aberrant dots per mm cortex in the cerebellar molecular layer of ACR-treated rats no matter before, after, or during ACR-exposure (p < 0.05). DSS significantly decreased the malondialdehyde level and increased the superoxide dismutase activity in brain of ACR-treated rats when DSS treated during ACR-exposure (p < 0.05). These findings suggest that DSS plays a protective role against ACR-developed neurotoxicity and, partly at least, through an anti-oxidative mechanism. And it is worthy to note that DSS treatment at the same time as ACR exposure plays a more effective protective role than before or after ACR exposure.

Effect of Withania somnifera root extract on haloperidol‐induced catalepsy in albino mice

The objective of the study was to evaluate the anticataleptic effect of Withania somnifera (WS) extract, on haloperidol-induced catalepsy in albino mice. Catalepsy was induced with haloperidol (1 mg/kg) i.p. in five groups of male albino mice (n = 6). Three groups received Withania somnifera extract (1.7, 4.25, 8.5 mg/kg) respectively, one group received scopolamine (1 mg/kg) and one group received the vehicle (1% gum acacia) orally, 30 min prior to haloperidol administration. Catalepsy was measured by using standard bar test at 30, 60, 90, 120 and 240 min. This constituted the acute study. For the chronic study, the drugs were administered for 6 more days. Catalepsy was again measured on day 7. Animals were then sacrificed by cervical dislocation and superoxide dismutase (SOD) activity was estimated in the brain. In this study, Withania somnifera extract treated groups showed a dose dependent reduction in cataleptic scores, both in the acute and chronic study. The SOD activity in brain was also found to be lowered in the WS (4.25 mg, 8.5 mg/kg) treated groups. In conclusion, Withania somnifera was found to be more efficacious than scopolamine in reversing haloperidol induced catalepsy. A clear correlation between the SOD levels and cataleptic scores was observed. We believe that the antioxidant properties of this drug could have contributed to the anticataleptic effect.

Red mold rice ameliorates impairment of memory and learning ability in intracerebroventricular amyloid β‐infused rat by repressing amyloid β accumulation

Amyloid beta (Abeta) peptide related to the onset of Alzheimer's disease (AD) damaged neurons and further resulted in dementia. Monascus-fermented red mold rice (RMR), a traditional Chinese medicine as well as health food, includes monacolins (with the same function as statins) and multifunctional metabolites. In this study, ethanol extract of RMR (RE) was used to evaluate neuroprotection against Abeta40 neurotoxicity in PC12 cells. Furthermore, the effects of dietary administration of RMR on memory and learning abilities are confirmed in an animal model of AD rats infused with Abeta40 into the cerebral ventricle. During continuous Abeta40 infusion for 28 days, the rats of test groups were administered RMR or lovastatin. Memory and learning abilities were evaluated in the water maze and passive avoidance tasks. After sacrifice, cerebral cortex and hippocampus were collected for the examination of AD risk factors. The in vitro results clearly indicate that RE provides stronger neuroprotection in rescuing cell viability as well as repressing inflammatory response and oxidative stress. RMR administration potently reverses the memory deficit in the memory task. Abeta40 infusion increases acetylcholinesterase activity, reactive oxygen species, and lipid peroxidation and decreases total antioxidant status and superoxide dismutase activity in brain, but these damages were potently reversed by RMR administration, and the protection was more significant than that with lovastatin administration. The protection provided by RMR is able to prevent Abeta fibrils from being formed and deposited in hippocampus and further decrease Abeta40 accumulation, even though Abeta40 solution was infused into brain continuously.

Induction of hepatic enzymes and oxidative stress in Chinese rare minnow ( Gobiocypris rarus) exposed to waterborne hexabromocyclododecane (HBCDD)

The objective of this study was to evaluate the sub-lethal toxicity of hexabromocyclododecane (HBCDD) in fish. Adult Chinese rare minnows as in vivo models were exposed to waterborne HBCDD from 1 to 500 μg/l for 14, 28 and 42 days. Hepatic CYP1A1 (ethoxyresorufin- O-deethylase, EROD) and CYP2B1 (pentaoxyresorufin- O-depentylase, PROD) activities were measured. At the same time, molecular biomarkers of oxidative stress were also assayed in the brain, including reactive oxygen species (ROS), lipid peroxidation products (thiobarbituric acid-reactive substances, TBARS), DNA damage and protein carbonyl, as well as superoxide dismutase (SOD) activity and glutathione (GSH) content. DNA damage was evaluated using the Comet assay on erythrocytes. Besides, the content of HBCDD in whole fish was determined after 42 days exposure. The results show that HBCDD could induce EROD and PROD at 500 μg/l after 28 days exposure, and at 100 to 500 μg/l after 42 days exposure ( P < 0.05), respectively. ROS formation in fish brain was observed to be increased in both time- and dose-dependent manner due to HBCDD exposure. The significant increases in TBARS and protein carbonyl contents occurred in fish brain after 28 and 42 days exposure ( P < 0.05). Significant DNA damage in erythrocytes by Comet assay was also found in the 100–500 μg/l exposure groups ( P < 0.05) after 42 days exposure. Moreover, significant depletion in brain GSH content occurred in all treated groups ( P < 0.05) and apparent inhibition in SOD activity in brain was observed in the groups of 10–500 μg/l concentrations during 42 days exposure. The results demonstrate that increasing duration of HBCDD exposure induced EROD and PROD activities, caused excess ROS formation, finally resulted in oxidative damage to lipids, proteins and DNA and decreased antioxidant capacities in fish. Chemical analysis of HBCDD in whole fish showed accumulation up to 654 μg/g wet weight.