Brain Thiobarbituric Acid Reactive Substances Research Articles

Glycitein prevents reserpine-induced depression and associated comorbidities in mice: modulation of lipid peroxidation and TNF-α levels.

Depression is a debilitating mood disorder affecting millions worldwide and continues to pose a significant global health burden. Due to the multifaceted nature of depression, the current treatment regimens are not up to mark in terms of their multitargeting potential and least side effect profile. Molecules within the isoflavone class demonstrate promising potential in alleviating depression and associated conditions, offering a multifaceted approach to manage mental health concerns. Therefore, the current study was designed to explore the potential of glycitein, an isoflavone in managing reserpine-induced depression and associated comorbidities in mice. Reserpine (0.5mg/kg; i.p.) administration for the first 3days induced depression and associated comorbidities as evidenced by increased immobility time in forced swim test (FST) and tail suspension test (TST), along with reduced locomotor activity in the open field test (OFT) and increased latency to reach the platform in the Morris water maze (MWM) test. Reserpine treatment also upregulated and downregulated the brain thiobarbituric acid reactive substance (TBARS) and glutathione (GSH) levels, respectively. Furthermore, reserpine administration also uplifted the level of TNF-α in the serum samples. Glycitein (3mg/kg and 6mg/kg; p.o.) treatment for 5days prevented the depressive effect of reserpine. It also improved the spatial memory at both dose levels. Moreover, in biochemical analysis, glycitein also reduced the brain TBARS and serum tumor necrosis factor-alpha (TNF-α) levels. Whereas, no significant effect was seen on the brain GSH level. Glycitein (6mg/kg) was found to be more effective than the 3mg/kg dose of glycitein. Overall results delineate that glycitein has the potential to manage depression and impaired memory by inhibiting lipid peroxidation and inflammatory stress.

Reversal of Neuralgia Effect of Beta Carotene in Streptozotocin-Associated Diabetic Neuropathic Pain in Female Zebrafish via Matrix Metalloprotease-13 Inhibition.

Beta carotene is a natural anti-oxidant agent, and it inhibits the matrix metalloprotease (MMP) activity. Diabetic neuropathic pain (DNP) is produced by cellular oxidative stress. The role of the beta carotene effect in diabetic neuropathic pain is not explored yet. The present study is designed for the evaluation of the palm oil mill effluent-derived beta carotene (PBC) effect in DNP in zebrafish. The DNP was induced by the intraperitoneal administration of streptozotocin (STZ). Blood glucose levels of above 15 mM were considered to be diabetic conditions. The zebrafish were exposed to test compound PBC (25, 50, and 100 µM), pregabalin (PG: 10 μM), and an MMP-13 inhibitor (CL-82198; 10 μM) for 10 consecutive days from day 11. The neuralgic behavioral parameters, i.e., temperature test, acetic acid test, and fin clip test were assessed on day 0 and the 7th, 14th, and 21st days. On the 22nd day, the blood glucose and MMP-13 levels and brain thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), and MMP-13 activity levels were estimated. The treatment of PBC ameliorated the DNP-associated behavioral and biochemical changes. The results are similar to those of PG and CL-82198 treatments. Hence, the PBC possesses a potentially ameliorative effect against DNP due to its potential anti-oxidant, anti-lipid peroxidation, and MMP-13 inhibitory actions.

Effects of Sargassum wightii Methanolic Extract on L-Methionine Induced Experimental Vascular Dementia like Syndrome in Albino Wistar Rats

Sargassum wightii is brown seaweeds with high nutritive value with natural bioactive compounds having diverse therapeutic activity. In recent years, research on Sargassum wightii has gain much interest in neuropharmacological field. Basing on neuroprotective effect of Sargassum wightii against Parkinson’s disease animal models, the possible protective effect on dementia is hypothesised. Addressing this question the present study was designed to investigate the effect of S. wightii on L-methionine induced vascular dementia like syndrome in male wistar albino rats. Vascular dementia was induced by oral administration of L-methionine (1.7 g/kg) per body weight for 4weeks S. wightii was given from day1 to day32. The neurobehavioral assessment was performed by Morris water maze test for learning and memory ability and blood sample was collected for serum nitrite and homocysteine analysis. The whole brain content was subjected to a series of biochemical analysis that included brain cholinesterase, malondialdehyde, reduced glutathione and histopathological examination. L-methionine impaired learning and memory, increased serum homocysteine and decreased serum nitrite level significantly (p<0.001). It also increased brain thiobarbituric acid reactive substances, reduced glutathione and increased acetylcholinesterase activity significantly (p<0.001). Sargassum wightii at 200mg/kg and 400mg/kg body weight reversed the L-methionine induced learning and memory deficits (p<0.01) and (p<0.001) respectively. The L-methionine induced biochemical alterations in serum and brain as well as histopathological aberration in cortex and hippocampus were restored by Sargassum wightii (p<0.01). This study concluded that Sargassum wightii ameliorated L-methionine induced vascular dementia like syndrome and provided a new concept in anti-dementia therapy as a neuroprotectants.

Evaluation of urinary 8-hydroxy-2-deoxyguanosine level in experimental Alzheimer's disease: Impact of carvacrol nanoparticles.

The present study aimed to compare the effect of carvacrol essential oil and carvacrol nanoemulsion against experimental Alzheimer's (AD). Forty male albino rats were used and divided into four groups as follow: control, AlCl3 induced AD, carvacrol oil treated and carvacrol nanoemulsion treated groups. Brain nor-epinephrine, serotonin and dopamine were analyzed by high performance liquid chromatography (HPLC). Levels of brain Thiobarbituric acid-reactive substances (TBARS), Superoxide dismutase (SOD), reduced glutathione (GSH), cholinesterase, and advanced oxidation protein product (AOPP) were evaluated. Urinary 8-hydroxyguanosine (8-OHdG) level was evaluated by HPLC. Brain Cyclooxygenase 1 and 2 (COX 1and 2) were analyzed by immunohistochemistry. AD induced by AlCl3 in rats was depicted by the significant increase in the neurotransmitters levels which is accompanied with high degree of oxidative stress that was revealed in the elevated level of urinary 8-OHdG along with significant elevation in AOPP, TBARS, and cholinesterase levels and a significant decrease in SOD and GSH; these results are confirmed by immunohistochemistry analysis of COX 1 and 2. On the other hand, the treatment with carvacrol oil and carvacrol nanoemulsion were capable of mitigate effects mediated by AlCl3 administration in treated rats. While the treatment with both approached succeeded to retract the negative impact of AlCl3; but the effect of carvacrol nanoemulsion was more notable than the essential oil. Carvacrol oil and carvacrol nanoemulsion were eminent to overturn AlCl3 induced brain AD which could be imputed to antioxidant and anti-inflammatory capabilities of carvacrol to alter oxidative stress effect. In extension; carvacrol nanoemulsion were evident to give more effective and efficient way in carvacrol delivery to pass through blood brain barriers and ameliorate brain changes.

Effect of Eclipta alba and Ocimum sanctum on haloperidol induced parkinsonism

The aim of the study is protective effect of compound Eclipta alba and Ocimum sanctum on Parkinsonism induced mice by haloperidol injection. Parkinsonism is neurodegenerative disease due to the deficiency of dopamine in brain. The pathological hallmark of Parkinson’s disease in the cell loss within substantia nigra pars compacta (SNpc) region and the disease is charactrised by bradykinesia, rigidity, postural instability, orofacial dyskinesia, muscular stiffness and tremor1. Mice were injected 1mg/kg haloperidol and then treated with test and standard substance for 15 days. The impairment in catatonia in mice were tested using catatonic activity. Biochemical analysis of brain homogenate was performed so ass to assess brain Thiobarbituric acid reactive substance (TBARS) level and reduced glutathione (GSH) and TNF-α level were measured to assess total oxidative stress. EA 300mg/kg and OS 400mg/kg show slightly change in catatonic activity in mice while EA 600mg/kg and 800mg/kg significantly change in catatonic activity. Furthermore, Eclipta alba and Ocimum sanctum prevent the haloperidol induced changes in the level of brain TBARS, GSH and TNF-α. From the results we conclude that Eclipta alba and Ocimum sanctum has protective action against impairment in catatonic activity and pathological damage due to oxidative stress induced by intraperitoneally injection of haloperidol in mice. 
 Keywords: Eclipta alba, Ocimum Sanctum, Parkinsonism, Anti-oxidant.

Neuroprotective effect of linagliptin against cuprizone-induced demyelination and behavioural dysfunction in mice: A pivotal role of AMPK/SIRT1 and JAK2/STAT3/NF-κB signalling pathway modulation

Multiple sclerosis is a chronic inflammatory demyelinating central nervous system disorder leading to serious neurological deficits. Linagliptin, a dipeptidyl peptidase-4 inhibitor, recently showed neuroprotective properties against neurodegenerative diseases. This study investigated the possible neuroprotective effect of linagliptin against cuprizone-induced demyelination in mice and its potential early-remyelinating properties. C57Bl/6 mice were fed chow containing 0.7% cuprizone for 1 week, followed by 3 weeks of a 0.2% cuprizone diet. Linagliptin (10 mg/kg/day, p.o.) was given for 3 weeks starting from the second week. Linagliptin treatment improved behavioural and motor abnormalities induced by cuprizone, as demonstrated by open field, rotarod and grip strength tests. In parallel, linagliptin lessened the demyelination through enhancing Olig2 gene expression, as shown by increased myelin basic protein, myelin proteolipid protein levels and Luxol fast blue-staining intensity. Linagliptin attenuated cuprizone-induced oxidative stress by decreasing brain thiobarbituric acid reactive substances along with restoring reduced glutathione levels. Linagliptin exerted an anti-inflammatory effect by reducing brain tumor necrosis factor-alpha. Interestingly, linagliptin diminished phosphorylated JAK2, phosphorylated STAT3 and NF-κB p65 protein expression while up-regulating phosphorylated AMP-activated protein kinase (p-AMPK) protein and SIRT1 gene expression levels. In conclusion, linagliptin exerted a neuroprotective effect in mice with cuprizone-induced demyelination possibly by modulating AMPK/SIRT1 and JAK2/STAT3/NF-κB signalling pathways.

Potential of carnosine, a histamine precursor in rat model of bilateral common carotid artery occlusion-induced vascular dementia.

The present study investigates the potential of Carnosine, a histamine precursor in rat model of bilateral common carotid artery occlusion (BCCAo)-induced vascular dementia (VaD). Wistar rats were subjected to BCCAo procedure under anaesthesia to induce VaD. The rats were subjected to Morris water maze (MWM) test (6th day onwards post-surgery). MWM test was employed to assess learning and memory of the animals whereby escape latency time, time spent in target quadrant and Path length (distance travelled) taken as important parameters. Serum nitrite level; Brain thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) levels; Brain acetylcholinesterase (AChE) activity; brain Myeloperoxidase activity (MPO) and neutrophil count were estimated as per standard procedures. BCCAo in rats produced a significant vascular endothelial dysfunction, as reflected by decrease in serum nitrite levels. Further, these animals showed poor performance on MWM, depicting impairment of learning and memory. There was a significant rise in brain oxidative stress level as indicated by increase in TBARS and decrease in GSH levels. An increase in brain AChE activity was also observed. Moreover, these rats also exhibited an increase in MPO activity and neutrophil infiltration in brain (as marker of inflammation). Treatment of Carnosine (200 and 400 mg/kg, i.p.)/Donepezil (0.3 mg/kg, i.p.) ameliorated BCCAo-induced memory deficits; endothelial dysfunction; biochemical and histopathological changes. It is concluded that Carnosine has shown efficacy in rat model of BCCAo-induced VaD and can be considered as an important therapeutic agent for the treatment of VaD.

Anti-aging and redox state regulation effects of A-type proanthocyanidins-rich cranberry concentrate and its comparison with grape seed extract in mice

We investigated the anti-aging and redox state regulation effects by A-type proanthocyanidins (PACs)-rich cranberry concentrate (CBC) and its comparison with B-type PACs-rich grape seed extract (GSE). Using the Q-Extractive mass spectrometry, PACs dimer A and B were identified as predominant phenolic compounds of CBC and GSE, respectively, while epicatechin was present in both extracts. Using the d-galactose-induced aging mice model, effects were investigated via an 8-week oral gavage considering water-soluble vitamin E as the positive control. Both CBC and GSE reduced hepatic and brain thiobarbituric acid reactive substances, and plasma 8-isoprostane levels by 30–57%, 24–30% and 11–62%, respectively, and decreased brain and plasma monoamine oxidase activities by 27–59% and 65–71%, respectively. CBC could improve hepatic glutathione peroxidase activity by 42%, while GSE increased hepatic superoxide dismutase activity by 13%. Therefore, both extracts exerted anti-aging effects probably via regulating in vivo redox state. However, neither generated any effect on catalase activities.

Caffeic Acid Phenethyl Ester (CAPE) Prevents Development of STZ-ICV Induced dementia in Rats.

Background:Chronic oxidative stress and inflammation severely affect the normal physiology of neurons and lead to neurodegenerative disorders such as Alzheimer's disease (AD). Polyphenols proved a boon in the prevention of dementia due to their antioxidant and neuroprotective potential. Caffeic acid phenethyl ester (CAPE) is a natural polyphenolic compound attributed with antioxidant, immunomodulatory, and neuroprotective properties.Objective:The present study investigates the effect of CAPE on experimental dementia in rats.Methods:Intracerebroventricle (ICV) injection of streptozotocin (STZ; 3 mg/kg) was given to Wistar rats (200 g, either sex) on days 1 and 3 to induce dementia of AD type. CAPE (3 and 6 mg/kg, i.p.) was administered to separate groups of rats for 28 successive days daily. Morris water maze and elevated plus maze served as exteroceptive behavioral models to measure the memory of the rats.Results:The present study illustrated that CAPE treatment for 28 consecutive days arrested the development of cognitive deficits in STZ-ICV-treated rats, that is, a significant (P < 0.05) reduction in the mean escape latency during acquisition trial and increased (P < 0.05) time spent in target quadrant during retrieval trial in Morris water maze test and reduction (P < 0.05) in transfer latency in elevated plus maze test. Furthermore, both the doses of CAPE when administered to rats that were previously treated with STZ-ICV prevented the rise of brain thiobarbituric acid reactive substance as well as TNF-α and simultaneously enhanced the GSH content.Conclusion:CAPE administration ameliorated STZ-ICV-induced dementia through the attenuation of oxidative stress and inflammation.SUMMARY Intracerebroventricular administration of streptozotocin (STZ-ICV) induced cognitive deficits, enhanced brain oxidative stress as well as inflammation in rats.Treatment with Caffeic Acid Phenethyl Ester (CAPE; dose 3 and 6 mg/kg, i.p.) for 28 days once daily, enhanced the memory and prevented the development of STZ-ICV-induced dementia in rats.The CAPE treated rats showed decrease in mean escape latency and increase in time spent in target quadrant in Morris Water Maze test. A decline in transfer latency of CAPE treated rats was observed in Elevated Plus Maze model.Profound rise in brain GSH levels and diminution of TBARS as well as TNF-α content was observed in brains of CAPE treated rats. Hence, the memory enhancing activity of CAPE against STZ-ICV-induced dementia is attributed to its robust antioxidant and anti-inflammatory property. Abbreviation used: AD: Alzheimer's disease, ANOVA: Analysis of Variance, aCSF: Artificial cerebrospinal fluid, CAPE: Caffeic acid phenethylester, EPM: Elevated plus maze, ELT: Escape latency time, GSH: Reduced glutathione, IL: Interleukin, ICV: Intracerebroventricular, MDA: Malondialdehyde, MEL: Mean escape latency, MWM: Morris water maze, NFTs: Neurofibrillary tangles, RNS: Reactive nitrogen species, ROS: Reactive oxygen species, SEM: Standard error of mean, STZ: Streptozotocin, TBARS: Thiobarbituric reactive substances, TSTQ: Time spent in target quadrant, TL: Transfer latency, TNF-α: Tumor necrosis factor alpha.

Anti‐aging and redox state regulation effects of type‐A proanthocyanidins‐rich cranberry concentrate and its comparison with grape seed extract in mice

In current study, we investigated whether type‐A proanthocyanidins (PACs)‐rich cranberry concentrate (CBC) exerts anti‐aging and redox state regulation effects and compared with the effects of type‐B PACs‐rich grape seed extract (GSE). Using the D‐galactose‐induced aging mice model, effects of both CBC and GSE were investigated via an 8‐week oral gavage administration considering vitamin E as the positive control. Results showed that both CBC and GSE reduce hepatic and brain thiobarbituric acid reactive substances (TBARS), presented as malonaldehyde (MDA) equivalents, and plasma 8‐isoprostane levels by 30%–57%, 24%–30% and 11%–62%, respectively, and decrease brain and plasma monoamine oxidase (MAO) activities by 27%–59% and 65%–71%, respectively. CBC is capable of improving hepatic glutathione peroxidase (GSH‐Px) activities by 42%, while GSE is able to enhance hepatic superoxide dismutase (SOD) activities by 13%. Therefore, CBC/GSE exerts anti‐aging effects probably via regulating in vivo redox state. Type‐A linked PACs regulate GSH‐Px activities while type‐B PACs mainly improve SOD activities, while neither generates any effect on catalase (CAT) activities. These findings provide pioneer in vivo evidence that type‐A PACs‐rich CBC has distinguished potential in aspects of anti‐aging and redox state regulation compared with well‐known type‐B PACs‐rich GSE, which deserve to be further concerned.Support or Funding InformationNational Natural Science Foundation of China (31201307)

2100-MHz electromagnetic fields have different effects on visual evoked potentials and oxidant/antioxidant status depending on exposure duration

The purpose of the present study was to investigate the duration effects of 2100-MHz electromagnetic field (EMF) on visual evoked potentials (VEPs) and to assess lipid peroxidation (LPO), nitric oxide (NO) production and antioxidant status of EMF exposed rats. Rats were randomized to following groups: Sham rats (S1 and S10) and rats exposed to 2100-MHz EMF (E1 and E10) for 2h/day for 1 or 10 weeks, respectively. At the end of experimental periods, VEPs were recorded under anesthesia. Brain thiobarbituric acid reactive substances (TBARS) and 4-hydroxy-2-nonenal (4-HNE) levels were significantly decreased in the E1 whereas increased in the E10 compared with their control groups. While brain catalase (CAT), glutathione peroxidase (GSH-Px) activities and NO and glutathione (GSH) levels were significantly increased in the E1, reduction of superoxide dismutase (SOD) activity was detected in the same group compared with the S1. Conversely, decreased CAT, GSH-Px activities and NO levels were observed in the E10 compared with the S10. Latencies of all VEP components were shortened in the E1 compared with the S1, whereas latencies of all VEP components, except P1, were prolonged in the E10 compared with the S10. There was a positive correlation between all VEP latencies and brain TBARS and 4-HNE values. Consequently, it could be concluded that different effects of EMFs on VEPs depend on exposure duration. In addition, our results indicated that short-term EMF could provide protective effects, while long-term EMF could have an adverse effect on VEPs and oxidant/antioxidant status.

Extra virgin olive oil modulates brain docosahexaenoic acid level and oxidative damage caused by 2,4-Dichlorophenoxyacetic acid in rats.

Oxidative stress is an important pathomechanism of neurological disorders such as Alzheimer disease and Parkinson disease, cardiovascular disorders and many others. This study sought to verify whether extra-virgin olive oil (EVOO), lipophilic fraction (OOLF) and hydrophilic fraction (OOHF) exerted a brain protective effect against the oxidative stress caused by 2,4-dichlorophenoxyacetic acid (2,4-D) pesticide at a dose of 5mg/kg body weight. 2,4-D, EVOO and its fractions were administered to rats by gavages for four consecutive weeks. Oxidative stress was assessed by measuring brain lipid peroxide level, acetylcholinesterase (AChE), antioxidant enzyme activities and fatty acid composition. 2,4-D induced a decrease in both plasma and brain acetylcholinesterase activity and a rise in Brain TBARS (Thiobarbituric acid reactive substances) level and antioxidant enzyme activities compared with the control group. These changes were partly reversed by either EVOO or its fractions oral administration to 2,4-D treated rats. EVOO enhanced a neuroprotective effect evaluated by the restoration of brain fatty acid composition especially the level of docosahexaenoic acid (DHA). Our results indicate that EVOO exerts a neuroprotective activity against oxidative damage in brain induced by 2,4-D, which could be attributed to its antioxidative property.

Amlodipine potentiates the protective effect of zonisamide on pentylenetetrazol-induced kindling in mice

Background: Zonisamide (ZON) and amlodipine (AML) were studied in different experimental models of epilepsy individually. However, combination of ZON and AML has not been explored yet. Hence, this study was aimed to evaluate the combination therapy of ZON and AML on pentylenetetrazol (PTZ)-induced kindling in mice. Materials and Methods: Swiss albino mice of either sex were randomly divided into five groups and each group containing 8 mice. Kindling was induced by PTZ (45 mg/kg/day on 8 th , 10 th and 12 th and 75 mg/kg/day on 14 th day). After treatment animals were observed for 30 min for behavioral analysis then animals were sacrificed and brain was taken out for biochemical analysis. Results: PTZ-significantly induced seizure was characterized by alteration in seizure score and latency as well as significantly increased in brain thiobarbituric acid reactive substance (TBARS) levels and significantly decreased in reduced glutathione, catalase (CAT) and superoxide dismutase (SOD). Treatment with ZON and AML significantly (P < 0.05, P < 0.01 and P < 0.001) resorted seizure score, latency, TBARS, reduced glutathione, CAT and SOD near to normal compared with pentylentetrazol treated rats. Conclusion: This study provides experimental evidence that treatment with both ZON and AML attenuated seizure and oxidative stress in PTZ-induced kindling mice.

The developmental effects of extremely low frequency electric fields on visual and somatosensory evoked potentials in adult rats

The purpose of our study was to investigate the developmental effects of extremely low frequency electric fields (ELF-EFs) on visual evoked potentials (VEPs) and somatosensory-evoked potentials (SEPs) and to examine the relationship between lipid peroxidation and changes of these potentials. In this context, thiobarbituric acid reactive substances (TBARS) levels were determined as an indicator of lipid peroxidation. Wistar albino female rats were divided into four groups; Control (C), gestational (prenatal) exposure (Pr), gestational+ postnatal exposure (PP) and postnatal exposure (Po) groups. Pregnant rats of Pr and PP groups were exposed to 50 Hz electric field (EF) (12 kV/m; 1 h/day), while those of C and Po groups were placed in an inactive system during pregnancy. Following parturition, rats of PP and Po groups were exposed to ELF-EFs whereas rats of C and Pr groups were kept under the same experimental conditions without being exposed to any EF during 68 days. On postnatal day 90, rats were prepared for VEP and SEP recordings. The latencies of VEP components in all experimental groups were significantly prolonged versus C group. For SEPs, all components of PP group, P2, N2 components of Pr group and P1, P2, N2 components of Po group were delayed versus C group. As brain TBARS levels were significantly increased in Pr and Po groups, retina TBARS levels were significantly elevated in all experimental groups versus C group. In conclusion, alterations seen in evoked potentials, at least partly, could be explained by lipid peroxidation in the retina and brain.

The relationship between oxidative stress markers and visual evoked potentials in different hypertension models.

We aimed to define the influence of different hypertension models on lipid peroxidation markers [conjugated dienes (CD) and thiobarbituric acid-reactive substances (TBARS)], antioxidant protection [paraoxonase-1 (PON1) activity] and visual evoked potential (VEP) changes in rats. The study was designed as four different hypertension models. Rats (n=84) were divided equally into six groups: Control group (C), Sham operated (Sham), Two kidney-one clip (2K-1C), One kidney-one clip (1K-1C), Deoxycorticosterone acetate (DOCA) and N-omega-nitro-L-arginine-methyl ester (L-NAME). Brain TBARS, serum lipids (total and lipoprotein bound cholesterols and triglycerides) CD and TBARS levels and PON1 activity were assayed. Comparisons were performed using ANOVA or Wilcoxon/Kruskal-Wallis tests. Pearson correlation and linear regression analysis were used to evaluate associations of independent predictors with hypertension. Mean arterial pressure, brain and serum lipid peroxidation markers, VEP latencies were significantly higher in four hypertensive groups compared with control and sham groups (p<0.05). Compared with controls, PON1 activity was decreased in DOCA, 1K1C and L-NAME groups (p<0.05). Serum PON1 activity was negatively correlated with lipid peroxidation markers and VEPs. In terms of VEP's records linear regression analysis showed that changes in N2 (B=1.51±0.34; p<0.001), P1 (B=-1.71±0.28; p<0.001), P3 (B=0.54±0.14; p<0.001), serum TBARS levels (B=0.94±0.24; p<0.001) and PON1 activity (B=0.05±0.02; p<0.01) were independently associated with elevated blood pressure. Lipid peroxidation measured in serum and brain was associated with increased electrophysiological alterations recorded as VEPs. This study might suggest that serum PON1 activity may be protective against brain and serum lipid peroxidation as well as electrophysiological alterations in the brain in different hypertension models.

Neuroprotective Effect of Thymoquinone on Repeated Immobilization Stress-Induced Oxidative Stress in Rats

The present study was designed to investigate the effect of Thymoquinone (TQ) in restraint stress- induced biochemical alterations in Wistar albino rats. Restraint stress was applied for 21 days (4 h/day) and 60 min before every stress exposure the rats were treated with two doses of TQ (5 and 10 mg/kg). In serum, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Interleukin-1β (IL-1β) Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α) were estimated. Thiobarbituric Acid Reactive Substances (TBARS), reduced Glutathione (GSH), nitrite and nitrate levels and Super Oxide Dismutase (SOD), Catalase (CAT), Glutathione-S-Transferase (GST), Glutathione-Reductase (GR) and Glutathione Peroxidase (GSH-Px) activities were estimated in brain. Interleukins and enzymatic activities in serum significantly elevated by the restraint stress and were ameliorated by both the doses of TQ treatment. In brain TBARS, nitrite and nitrate levels significantly elevated due to restraint stress, the TQ treatment brings back to normal levels. Restraint stress significantly decreased in oxidative enzyme activities as the SOD, CAT, GST, GSH-Px and GR. TQ treatments significantly enhanced the activities compared to untreated stressed rats. Present results revealed that, TQ reduced the restraint stress-induced oxidative process in terms of above mentioned biochemical parameters. Thus, in view of its antioxidative nature, TQ may be developed as an effective therapeutic agent for stress-induced oxidation and CNS depression.

Curcumin Rescues Aging-Related Loss of Hippocampal Synapse Input Specificity of Long Term Potentiation in Mice

Curcumin has neuroprotective effect and could enhance memory. However, the mechanisms underlying the protection of curcumin on aging-related memory decline are not well understood. In this study, high frequency stimulation (HFS)-induced long term potentiation (LTP) was evaluated by a cellular model of memory formation. A two-input stimulation paradigm was used to record the potentiation as well as synapse input specificity. The data suggested that an N-Methyl-D-aspartate receptors (NMDAR) -dependent LTP was inducible in adult hippocampal slices with a characteristic of synapse input specificity. It also indicated that aging resulted in a reduction in LTP but more importantly a loss of synaptic input specificity. The reason behind the above conclusions is that LTP induction is more dependent on the calcium channel. This is due to a switch of the dependence of LTP induction to voltage-dependent calcium channel (VDCC) compared to NMDA receptors. Curcumin administration recovers input specificity by re-establishing NMDA receptor dependence of induction. In addition, curcumin administration ameliorated aging-related increase of brain thiobarbituric acid-reactive substances and elevated aging-related decrease of glutathione in hippocampus. It is then concluded that curcumin modulates hippocampal redox status and restores aging-related loss of synapse input specificity of HFS-induced LTP by switching VDCC calcium source into NMDA receptor-dependent one.

Antioxidant, antihemolytic, and inhibitory activities of endemic Primula heterochroma against Fe2+-induced lipid peroxidation and oxidative stress in rat brain in vitro

Context: The genus Primula (Primulaceae) has been used in traditional medicine to treat convulsion and microbial or viral infections.Objective: In the present study, we evaluate antioxidant, antihemolytic, and protective effects of flavonoid-rich fractions of endemic Primula heterochroma Stapf. (Primulaceae) against Fe2+-induced lipid peroxidation and oxidative stress in rat brain in vitro.Materials and methods: Aerial parts of plant were defatted and extracted with 60% acetone. Then, 60% acetone extract was fractionated sequentially with n-hexane, ethyl acetate, and water. Antioxidant activity of fractions was evaluated by employing six different assays, i.e., 1,1-diphenyl-2-picryl hydrazyl (DPPH) and hydrogen peroxide scavenging, metal chelating and reducing power activities and hemoglobin-induced linoleic acid system and Fe2+-induced lipid peroxidation and oxidative stress in rat brain. Also, its antihemolytic activity was determined using 2,2′-azobis(2-amidinopropane) dihydrochloride-induced hemolysis in rat erythrocyts.Results: Among the flavonoid-rich fractions of Primula heterochroma, aqueous fraction demonstrated the most protective effect through decreasing brain thiobarbituric acid reactive substances (TBARS) levels at a dose 200 μg mL−1 (40%, p < 0.001 versus iron group). Also, the aqueous fraction showed better activity in Fe2+ chelating (89 ± 3.8 μg mL−1) and DPPH radical scavenging (394.4 ± 18.4 μg mL−1) models than other fractions. The probable protective mechanism of flavonoid-rich fractions may be attributed to their Fe2+ chelating, DPPH radical scavenging and reducing power activities. Also, the n-hexane fraction demonstrated a higher protective effect in the hemoglobin-induced linoleic acid system and 2,2′-azobis(2-amidinopropane) dihydrochloride-induced hemolysis (67 ± 2.6 μg mL−1).Discussion and conclusion: Results of this study demonstrate Primula heterochroma is a rich source of natural antioxidant compounds.

Neuro-protective effect of Mentha extract against oxidative stress in pre-treated gamma irradiated Swiss albino mice

The damaging effect of ionizing radiation on body systems on one hand, and the development of radio-protective agents on the other hand, have gained increased attention in the last decades. In the present study, male Swiss albino mice exposed to six gray gamma irradiation, exhibited significant increase in brain thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), and free radicals such as hydrogen peroxide (H2O2). Significant decrease in the levels of reduced glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) contents, acetylcholinestrase (AchE), and the neurotransmitters dopamine (DA), serotonin (5-HT), and acetylcholine (Ach), was also documented. In addition, the levels of serum electrolytes sodium (Na), calcium (Ca), zinc (Zn), magnesium (Mg), and cupper (Cu) decreased significantly, while the levels of potassium (K), and iron (Fe) increased significantly. Additionally, some Lewy body aggregations were detected. On the other hand, pretreatment of gamma irradiated mice with Mentha piperita extract (1g /1Kg body weight /day) significantly abolished radiation induced elevations of TBARS, NO, H2O2, K and Fe levels, as well as significantly ameliorated the GSH, GST, SOD, AchE, DNA, RNA, Na, Ca, Zn, Mn, Cu and the mentioned-above neurotransmitters levels. In conclusion, Mentha extract may provide a significant level of protection against radiation-induced oxidative stress. It might have improved the antioxidant defense system in pre-treated mice also. Key words: Gamma irradiation, Mentha piperita, oxidative stress, neuroprotective radioprotective agent, endogenous antioxidant system.

Cypermethrin induced damage in genomic DNA and histopathological changes in brain and haematotoxicity in rats: The protective effect of sesame oil

The protective effect of sesame oil against cypermethrin-induced brain toxicity was studied. Female rats were orally treated with cypermethrin, sesame oil and their combination for 30 consecutive days. The results showed that cypermethrin increased thiobarbituric acid-reactive substances (TBARS), and decreased glutathione (GSH) and the activities of the antioxidant enzymes. Brain injury was confirmed by histopathological changes and DNA damage. Also, the reduction in the activities of acetylcholinesterase and monoamine oxidase (AChE & MAO), total protein, albumin and body weight, and the induction in triacylglycerol and cholesterol have been observed due to cypermethrin toxicity. Animals treated with sesame oil and cypermethrin together showed that brain TBARS and plasma triacylglycerol and cholesterol returned to the control level which indicating a protective effect of sesame oil. Also, sesame oil was able to attenuate the decrease in total protein, albumin, triacylglycerol and cholesterol, GSH, AChE and antioxidant enzymes induced by cypermethrin. In addition, sesame oil protected the brain histological changes and fragmentation of genomic DNA in animals treated with cypermethrin. The present results showed a protective effect of sesame oil against the cypermethrin induced brain toxicity and this could be associated mainly with the attenuation of the oxidative stress and the preservation in antioxidant enzymes.