Brain Malondialdehyde Research Articles

The Hepatoprotective mechanisms of 17β-estradiol after traumatic brain injury in male rats: Classical and non-classical estrogen receptors

Protective effects of estrogen (E2) on traumatic brain injury (TBI) have been determined. In this study, the hepatoprotective effects of E2 after TBI through its receptors and oxidative stress regulation have been evaluated. Diffuse TBI induced by the Marmarou method in male rats. G15, PHTPP, MPP, and ICI182–780 as selective antagonists of E2 were injected before TBI. The results indicated that TBI induces a significant increase in liver enzymes [Alkaline phosphatase (ALP), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Glutamyl transferase (GGT)], and oxidants levels [Malondialdehyde (MDA), Nitric oxide (NO)] and decreases in antioxidant biomarkers [Glutathione peroxidase (GPx) and Superoxide dismutase (SOD)] in the brain and liver, and plasma. We also found that E2 significantly preserved levels of these biomarkers and enzymatic activity. All antagonists inhibited the effects of E2 on increasing SOD and GPx. Also, the effects of E2 on brain MDA levels were inhibited by all antagonists, but in the liver, only ICI + G15 + E2 + TBI group was affected. The impacts of E2 on brain and liver and plasma NO levels were inhibited by all antagonists. The current findings demonstrated that E2 probably improved liver injury after TBI by modulating oxidative stress. Also, both classic (ERβ, ERα) and non-classic [G protein-coupled estrogen receptor (GPER)] receptors are affected in the protective effects of E2.

The effect of sulfasalazine in pentylenetetrazole-induced seizures in rats.

We aimed to reveal the anti-convulsant effects sulfasalazine and its mechanism in pentylenetetrazole (PTZ)-induced seizures in rats. Forty-eight male Wistar albino rats (200-250 g) were randomly divided into two groups: 24 for electroencephalography (EEG) recording (group A) and 24 for behavioral studies (group B). About 70 mg/kg PTZ was used for behavioral studies after sulfasalazine administration and 35 mg/kg PTZ was used for EEG recording after sulfasalazine administration. Electrodes were implanted on the dura mater over the left frontal cortex and the reference electrode was implanted over the cerebellum for EEG recording. Racine’s convulsion scale, first myoclonic jerk onset time, spike percentages, brain malondialdehyde (MDA), superoxide dismutase (SOD), and prostaglandin F2α (PGF2α) levels were evaluated between the groups. First myoclonic jerk onset time was significantly shorter in the saline group than both 250 and 500 mg/kg sulfasalazine groups (P<0.05). Racine's convulsion scores were significantly lower in the 250 and 500 mg/kg sulfasalazine groups than the saline group (P<0.05, P<0.001). The two sulfasalazine groups had lower spike percentages than the saline group (P<0.05). Significantly lower MDA and PGF2α levels were observed in the 250 and 500 mg/kg sulfasalazine groups compared with the saline group (P<0.05, P<0.001, respectively). SOD increased significantly in both sulfasalazine groups compared with the PTZ+saline group (P<0.05). Our study demonstrated that sulfasalazine had protective effects on PTZ-induced convulsions by protecting against oxidative and inflammatory damage associated with PTZ.

Antioxidative effects of uridine in a neonatal rat model of hyperoxic brain injury

Premature birth is a major problem that results in an increased risk of mortality and morbidity. The management of such infants consists of supraphysiological oxygen therapy, which affects brain development due, in part, to the deterioration caused by reactive oxygen species (ROS). We showed previously that exogenously administered uridine provides neuroprotection in a neonatal rat model of hyperoxic brain injury. Hence, the aim of the present study was to investigate the effects of uridine on ROS in the same setting. Hyperoxic brain injury was induced by subjecting a total of 53 six-day-old rat pups to 80% oxygen (the hyperoxia group) for a period of 48 h. The pups in the normoxia group continued breathing room air (21% oxygen). Normoxia + saline or hyperoxia + saline or hyperoxia + uridine 100 mg/kg or hyperoxia + uridine 300 mg/kg or hyperoxia + uridine 500 mg/kg was injected intraperitoneally (i. p.) 15 min prior to the hyperoxia procedure. The pups were decapitated and the brains were homogenized to analyze superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), myeloperoxidase (MPO), and malondialdehyde (MDA) enzymes as well as DJ-1 (protein deglycase DJ-1) — an oxidative stress-sensitive protein. Hyperoxia-induced may cause overproduction of oxygen radicals and the oxidant/antioxidant balance may be disturbed in the brain. Brain MPO and MDA levels were significantly increased in saline-receiving pups exposed to hyperoxia. Brain SOD and GSH-Px levels were significantly decreased in saline-receiving pups exposed to hyperoxia. Our results showed that uridine administration prevented the hyperoxia-induced decrease in SOD and GSH-Px while counteracting the hyperoxia-induced increase in MPO and MDA in a dose-dependent manner. Uridine also increased the DJ-1 levels in brains of rat pups subjected to hyperoxia. These data suggest that uridine exhibits antioxidative properties which may mediate the protective effects of uridine in a neonatal rat model of hyperoxic brain injury.

Amelioration of neurotoxicity induced by esfenvalerate: impact of Cyperus rotundus L. tuber extract

The main objective of this current study was to assess the protective role of Cyperus rotundus L. (CR) extract against oxidative stress, neurotoxicity, and inflammation induced by esfenvalerate in rats. The total phenol (TP) and total tannins (TT) were estimated by Folin ciocalteu and total flavonoids were evaluated by aluminum chloride methods. The methanol: acetone: H2O with ratio 2:2:1 extract of C. rotundus tubers was determined antioxidant activity by DPPH, ABTS•+scavenging activities, and ferrous chelating, reducing power activities assays. Antioxidant activities of C. rotundus tuber extract exhibited 224.25, 191.47, and 218.77 μg/ml against 2,2-diphenyl-1-picrylhydrazyl (DPPH•), and 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•) radicals and Fe2+-chelating, respectively expressed as IC50 while reducing power showed 119.88 μg/ml expressed as EC50. C. rotundus tuber extract’ analysis showed a presence of several phenolic and flavonoid compounds identified by HPLC. Albino Wistar rats were divided into normal control, C. rotundus alone treated esfenvalerate, and treated (Esfenvalerate + CR) groups. The dose of C. rotundus extract was100 mg /kg BW, while the dose of esfenvalerate was 0.533 mg/kg BW orally. Administration of esfenvalerate decreased the levels of brain reduced glutathione (GSH), and paraoxnase-1(PON-1), and decreased acetylcholinesterase activity along with increasing the levels of brain malondialdehyde (MDA) and nitric oxide (NO), furthermore, increased serum tumor necrosis factor-alpha (TNF-α), adiponectin, and lipocalin-2. On the other hand, treatment with C. rotundus extract significantly showed a protective effect against esfenvalerate by ameliorating levels of antioxidant enzymes, acetylcholine esterase, and inflammatory markers. The present study elicited a prophylactic effect of C. rotundus against neural damage induced by esfenvalerate in experimental rats.

Beneficial effect of black rice ( Oryza sativa L. var. japonica ) extract on amyloid β-induced cognitive dysfunction in a mouse model.

Alzheimer's disease (AD) is an age-dependent progressive neurodegenerative disease, resulting in memory loss and cognitive dysfunction. The accumulation of amyloid β (Aβ) has been identified as the most important risk factor for AD. Black rice (BR; Oryza sativa L. var. japonica), which is widely consumed in Asia, is a good source of bioactive compounds including anthocyanins. Therefore, the aim of the present study was to evaluate the protective effect of BR extracts against Aβ25-35-induced memory impairment in an in vivo AD mouse model. After intracerebroventricular injection of Aβ25-35, mice were treated with BR extract supplementation for 14 days. Memory and cognition function were evaluated over this period in both treated and untreated animals using T-maze, novel object recognition and Morris water maze tests. After behavioral tests, malondialdehyde (MDA) and nitric oxide (NO) concentrations in brain, liver and kidney tissues were analyzed. Mice treated with Aβ25-35 had impaired memory and cognitive function; however, mice administered BR extract (100 mg/kg/day) demonstrated an improvement in cognition and memory function compared with the Aβ25-35-injected control group. Furthermore, injection of Aβ25-35 significantly increased MDA and NO generation in the brain, liver and kidney of mice. However, the group administered with BR extract had significantly inhibited lipid peroxidation and NO generation in the brain, liver and kidney. In addition, the protective effect of BR on lipid peroxidation and NO production by Aβ25-35 was stronger in the brain compared with other tissues. Collectively, these findings suggested that BR supplementation may prevent memory and cognition deficits caused by Aβ25-35-induced oxidative stress.

Neuroserpin extends the time window of tPA thrombolysis in a rat model of middle cerebral artery occlusion.

Tissue-type plasminogen activator (tPA) is characterized as an effective drug for early thrombolytic therapy in acute cerebral infarction (ACI). However, tPA will increase the risk of hemorrhage if it is used beyond the treatment time window. The study aims to explore the effects of neuroserpin (NSP) on the time window of tPA thrombolysis in ACI and the underlying mechanism. The middle cerebral artery occlusion (MCAO) model was constructed in rats, which were randomly divided into six groups: sham operation group, infarction group, 1-hour thrombolysis group, 1-hour thrombolytic + NSP intervention group, 4-hour thrombolytic group, and 4-hour thrombolysis + NSP intervention group. The neurological changes in rats were evaluated by modified neurological severity scores and rota-rod test. The brain edema and cerebral infarction area were evaluated by dry-wet method and triphenyl tetrazolium chloride staining. The blood-brain barrier (BBB) integrity was examined by Evans blue method. The expressions of malondialdehyde, superoxide dismutase, and glutathione peroxidase in brain were also investigated. The expression of caspase-3 and Bcl-2 in brain tissue and apoptosis of neurons were examined by Western blot analysis and toluidine blue staining. tPA thrombolysis significantly attenuated the neurological impairment in rats with MCAO at 1 hour. Conversely, the effect of tPA thrombolysis at 4 hours after MCAO did not significantly help the recovery of neurological function. However, a combination of tPA treatment and NSP treatment at 4 hours after MCAO markedly ameliorated the neurological impairment, cerebral edema, cerebral infarction volume, BBB injury, oxidative stress products, and neuron apoptosis. NSP can probably expand the time window for tPA treatment to reduce neurological impairment in ACI.

Protective effect of fisetin against subchronic chlorpyrifos-induced toxicity on oxidative stress biomarkers and neurobehavioral parameters in adult male albino mice.

Chlorpyrifos (CPF), a chlorinated organophosphate insecticide that is widely used in agriculture and public health, has neurotoxic effects in animals. In addition to acetylcholinesterase inhibition, CPF has been shown to induce alterations such as oxidative stress and lipid peroxidation. Fisetin is a dietary flavonol that protects the brain tissue against oxidative stress by modulating the activity of antioxidant enzymes. This study was designed to investigate the protective role of fisetin against brain oxidative damages and neurobehavioral parameters induced by subchronic oral exposure to CPF in albino mice. Adult albino mice (males, n = 32, weighing 20 ~ 25g) were assigned randomly into 4 groups and treated accordingly for 7weeks as follows: Group 1(S/OIL): served as the control group and were given 2ml/kg of soya oil; Group 2 (CPF): received CPF (6.6mg/kg; 1/5th of the LD50); Group 3 (FIS): fisetin (15mg/kg) and Group 4 (FIS + CPF): received fisetin at 15mg/kg, followed by CPF (6.6mg/kg) 30min later. Co-treatment with FIS + CPF mitigated the increase in brain malondialdehyde concentration (0.28 ± 0.02nmol/mg) and orchestrated the increase in the activities of catalase (81.35 ± 7.26 µ/mg), superoxide dismutase (93.03 ± 6.63IU/mL), glutathione peroxidase (68.76 ± 3.554nmol/mL) and acetylcholinesterase (11.59 ± 0.72nmol/min/mL) when compared to the CPF group. The result showed that deficits in motor strength and excitability scores induced by subchronic CPF were mitigated by fisetin administration. It was concluded that fisetin has a protective potential in mitigating against oxidative stress and damages in the brain tissues, induced by subchronic exposure to CPF in adult male albino mice.

Arthrophytum scoparium Extract Improves Memory Impairment and Affects Acetylcholinesterase Activity In Mice Brain.

Arthrophytum scoparium (Pomel) Iljin (Amaranthaceae family) has been widely used in traditional Tunisian medicine to treat many disorders such as migraine, headache, and neurological disorders. This study investigates the effect of Arthrophytum scoparium Aqueous Extract (ASAE) on cognitive impairments and oxidative injury induced by galactose (10%) in a mouse model. The mice were divided randomly into 4 experimental groups, including the control group (saline water 9 ‰), Galactose group, Scop group (300 mg/kg/d), and Scop+Gal group (300 mg/kg/d). Mice received the corresponding solutions by intraperitoneal injection (i.p.) for 7 days before the Y-maze active tests. Galactose 10% was given to all groups except control and Scop groups, 30 min before the trial. Levels of Acetylcholinesterase Activity (AChE), Ascorbic Acid (AA), Gluthatione (GSH) and Malondialdehyde (MDA) in mice brains were examined. Chronic administration of galactose significantly impaired cognitive performance in Y maze, caused marked oxidative damages and a significant increase in the acetylcholinesterase activity as compared to other groups. On the contrary, ASAE (300 mg/kg) treatment suppressed galactoseinduced oxidative damage by ameliorating the increased levels of GSH and AA. Moreover, ASAE treatment reduced brain AChE activities in the galactose-induced model. These findings suggest that ASAE exerts potent anti-amnesic effects via the modulation of cholinergic and antioxidant activities. The observed pharmacological activities should be further evaluated by detailed experimental studies and validated by clinical trials.

Effects of maternal dietary vitamin E on the egg characteristics, hatchability and offspring quality of prolonged storage eggs of broiler breeder hens.

This research aims to evaluate the effects of maternal vitamin E (VE) dietary supplementation on the egg characteristics, hatchability and antioxidant status of the embryo and newly hatched chicks of prolonged storage eggs. A total of 576 75-week-old Ross 308 breeder hens were randomly allocated into three dietary VE treatments (100, 200 and 400mg/kg) with 6 replicates of 32 hens, for a 12-week feeding trial. At week 12, a total of 710 eggs were collected over a 5-day period, and eggs per treatment were attributed into 5 replicates and stored for 14days until incubation. The egg yolk, trunk and head of 7-day-old embryo and the serum, liver, brain and yolk sac of newly hatched chicks were sampled for the evaluation of antioxidant status. Results showed that as maternal dietary VE levels increased, yolk α-tocopherol concentration increased (p<.05). Compared with 100mg/kg VE, the use of 200 and 400mg/kg VE increased the hatchability of set/fertile eggs and total antioxidant capacity (T-AOC) of liver and serum in chicks (p<.05), and decreased both the early embryonic mortality and the malondialdehyde (MDA) content of trunk and head in 7-day-old embryos (p<.05); moreover, 400mg/kg VE increased the yolk T-AOC (p<.05) and decreased yolk and brain MDA content of chicks (p<.05). Brain T-AOC of chicks in 200mg/kg VE group was improved compared to that of chicks in 100mg/kg VE group (p<.05). In conclusion, maternal dietary VE at 200 or 400mg/kg could increase hatchability by decreasing early embryonic mortality and increasing the antioxidant status of egg yolk, embryo and newly hatched chicks as breeder egg storage was prolonged to 14-18days. The suitable VE level for the broiler breeder diet was 200mg/kg as breeder egg storage was prolonged.

Beneficial effects of (-)-epigallocatechin-3-O-gallate on diabetic peripheral neuropathy in the rat model.

Diabetic neuropathic pain is characterized by spontaneous pain with hyperalgesia and allodynia. We investigated whether (-)-epigallocatechin-3-O-gallate could improve diabetic neuropathic pain development through hypoglycemic, hypolipidemic, antioxidant, and anti-inflammatory effects. Diabetes was induced in rats by streptozotocin (55 mg/kg/once) and treated with (-)-epigallocatechin-3-O-gallate (25 mg/kg/orally/once/daily/5 weeks). Diabetic rats showed an increase in serum levels of glucose, nitric oxide, triglyceride, total cholesterol, and low-density lipoprotein-cholesterol with a decrease in high-density lipoprotein-cholesterol and body weight. Also, there was an elevation in brain malondialdehyde with a marked reduction in brain levels of glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase. Furthermore, diabetic rats showed a clear reduction in plasma levels of insulin and an increase in plasma cytokines (interleukin-6 and tumor necrosis factor-α). Moreover, diabetic rats exhibited hyperalgesia as indicated by a hot plate, tail immersion, formalin, and carrageenan-induced edema tests as well as brain histopathological changes (neuron degeneration, gliosis, astrocytosis, congestion and hemorrhage). (-)-Epigallocatechin-3-O-gallate treatment ameliorated alterations in body weight, biochemical parameters, pain sensation, and histopathological changes in brain tissue. (-)-Epigallocatechin-3-O-gallate offers promising hypoglycemic, hypolipidemic, antioxidant and anti-inflammatory effects, which can prevent the development and progression of diabetic neuropathic pain.

Stressor and Multi‐Organ Antioxidant Profile following Early Life Maternal Deprivation in Albino Rats

One‐week‐old albino pups were separated from their dams for a period of 24 to 48 hours. Sixty (60) rats were divided into 6 equal groups (n=10). Group A rats were separated for 24 hours and given glucose subcutaneously (200mg/kg) at 2, 7, 12 and 22 hours post maternal deprivation (MD). Group B rats received no intervention or treatment. Group C was subjected to 24 hours MD and given distilled water at regular intervals as group A. Group D rats had no MD but were given distilled water at same intervals as group A. Groups E and F were subjected to 48‐hour MD and administered Glucose or distilled water respectively at 2, 7, 17, 22, 27, 32, 42 and 47 hours post MD. Blood and tissue samples were collected for biochemical analyses.Significant weight gains were recorded in the groups with no maternal deprivation. The 48‐hour MD group supplemented with glucose competed favorably, showing a 7.2% weight gain over two days. At the other end of the spectrum, the 24‐hour MD supplemented with distilled water group recorded a 3% weight loss.The results show a graded rise in brain total protein values with time, with the highest values recorded in the 48‐hour MD + distilled water group and the lowest in the 24‐hour MD + distilled water group. Other organs showed no significant differences between groups. There were no differences across groups in all the organs assayed for nitric oxide (NO) either. For specific oxidative stress markers, Brain malondialdehyde (MDA) levels appear to be significantly lowest at the 48‐hour MD + distilled water group when compared with other groups. This correlated with a time dependent depletion in the brain antioxidant enzyme profiles studied. Brain GST, GPX and SOD all show highest concentrations in the 24‐hour MD + glucose group with lowest values recorded in the 48‐hour MD + distilled water group. Other organs did not show marked differences in between groups.Cortisol levels were assayed to evaluate stressor responses. The highest concentrations were seen in the 48‐hour MD + glucose group with the least seen in the 24‐hour MD + distilled water group. Consequently, parenteral administration of fluids (water and glucose) are a poor substitute for maternal nutrition although initial evidence points towards potential decline in brain antioxidant profile.Support or Funding InformationThe Tertiary Education Trust Fund (TETFUND) of Nigeria. The Faculty of Veterinary Medicine, University of Abuja, Nigeria.The Cardiorenal research group, Faculty of Veterinary Medicine, University of Ibadan; especially Professor Adeolu A. Adedapo, Dr. Tayo O. Omobowale, Dr. Ademola A. Oyagbemi and Dr. Jerry Afolabi.Brain Total Protein (TP) and Malondialdehyde (MDA) charts of all the groupsFigure 1

Prenatal and early postnatal food restrictions cause changes in brain oxidative status and orexigenic/anorexigenic hormones in the offspring of rats: prevention by quercetin and kaempferol

Brain oxidative signaling pathways have been identified as important targets for alleviating food deprivation-induced changes in metabolic gate-ways. Previous studies have shown that prenatal and early postnatal malnutrition alters leptin and ghrelin signaling via oxidative pathways. Thus, it has been hypothesized that agents with antioxidant properties might be beneficial for the mitigation of prenatal and early postnatal food scarcity-induced oxidative damage. Quercetin and kaempferol are natural bioflavonoids with proven antioxidant properties. In this study, we evaluated their effects on prenatal maternal food consumption, maternal and pup weights, biomarkers of orexigenic and anorexigenic hormones and oxidative stress in rats. Rats were allotted into different treatment groups (n ​= ​6) in three different experiments (prenatal, postnatal food-deprivations or both). Prenatal-food restriction (PrNFR) was induced by 50% of ad libitum accessible diet during pregnancy till parturition and postnatal-food restriction (PsNFR) was simulated by litter-enlargement to 16 pups per mother from postnatal day (PND) 2. Rats in each experiment were concurrently treated with vehicle (10 ​mL/kg), quercetin (50, 100 and 200 ​mg/kg, p.o.) or kaempferol (50, 100 and 200 ​mg/kg, p.o.) respectively. A third experimental group consisted of both protocols. Quercetin and kaempferol dose-dependently increased the body weights of pups exposed to PrNFR, PsNFR and PrNFR-PsNFR at PNDs 1–22 respectively. Both compounds increased maternal body weights but attenuated maternal food-intake at prenatal days 7 and 14 due by PrNFR. Quercetin and kaempferol reduced brain malondialdehyde concentrations and increased glutathione levels in PrNFR, PsNFR and PrNFR-PsNFR-exposed offspring of rats. Importantly, quercetin and kaempferol significantly (p ​< ​0.05) prevented PrNFR-, PsNFR- or PrNFR-PsNFR-induced alterations in leptin and ghrelin levels. Cumulatively, quercetin and kaempferol increased pup and maternal weights and attenuated maternal food-intake of rats submitted to PrNFR, PsNFR and PrNFR-PsNFR respectively, likely via nutrigenomic modulations of orexigenic/anorexigenic hormones and inhibition of brain oxidative stress.

Effects of fullerene C60 supplementation on gut microbiota and glucose and lipid homeostasis in rats

The effects of twelve weeks of supplementation with fullerene C60 olive/coconut oil solution on a broad spectrum of parameters in rats were examined. The tissue bioaccumulation of C60 was shown to be tissue-specific, with the liver, heart, and adrenal glands being the organs of the greatest, and the kidney, brain, and spleen being the organs of the smallest accumulation. C60 did not change aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase serum activities level, nor the damage of liver cells DNA. There were no effects of fullerene on prooxidant-antioxidant balance in the liver, kidney, spleen, heart, and brain, nor any visible harmful effects on the liver, heart, aorta, spleen, kidney, and small intestine histology. Fullerene changed the gut microbiota structure towards the bacteria that ameliorate lipid homeostasis, causing a serum triglycerides concentration decrease. However, C60 significantly increased the insulin resistance, serum ascorbate oxidation, and brain malondialdehyde and advanced oxidation protein products level. The deteriorative effects of C60 on the brain and serum could be attributed to the specific physicochemical composition of these tissues, potentiating the C60 aggregation or biotransformation as the key element of its pro-oxidative action.

Effect of Thymoquinone against Aluminum Chloride-Induced Alzheimer-Like Model in Rats: A Neurophysiological and Behavioral Study

Abstract Background: Alzheimer Disease (AD) is a progressive neurodegenerative disorder characterized by oxidative stress, neuro-inflammation and synaptic dysfunction, which caused in part by abnormal aggregation of senile plaques and neu-rofibrillary tangles outside and inside the cerebral neurons, respectively. Thymoquinone (TQ) is the major bioactive ingredient of the volatile oil of Nigella sativa seed and it possess anti-inflammatory and antioxidant effects in some neuronal diseases. Aim of Study: To evaluate the neuroprotective potential of TQ on the oxidative stress status of the brain in aluminum chloride (AlCl3)-induced AD in rats. Material and Methods: Thirty adult male Sprague Dawley albino rats were used in this study. They were randomly divided into 3 groups. Group 1 (control group). Group 2 (AD group): Supplemented orally with AlCl3 (17mg/kg/day) for 4 weeks. Group 3 (TQ/AD group) supplemented concomitantly with oral TQ (10mg/kg/day) and AlCl3 (17mg/kg/day) for 4 weeks. At the end of the experiment, spatial working memory was assessed using the Y-maze spontaneous alternation test. Then, serum levels of Malondialdehyde (MDA) and Glutath-ione Peroxidase Enzyme (GPX) were assessed. Then, the rats were sacrificed and the brain tissue homogenate content of tau protein, AR and acetyle choline were determined. Results: In AD group, spatial working memory was im-paired as indicated by a significant decline of Spontaneous Alteration Performance (SAP%) at Y-maze behavior test. Also, AR, tau protein, acetyle choline in brain and serum MDA were significantly increased with a significant decrease of serum GPX. Co-administration of TQ with AlCl3 in TQ/AD group, significantly decreased AR, tau protein, acetyle choline in brain and serum MDA and increased (SAP%) and serum GPX. Conclusion: TQ could mitigate the neurodegenerative markers and oxidative stress indices encountered in AD, presumably via its antioxidant and anti-inflammatory effects.This may implement TQ as an adjuvant alternative medical strategy in ameliorating this devastating disease

Capsaicin Exerts Anti-convulsant and Neuroprotective Effects in Pentylenetetrazole-Induced Seizures.

The transient receptor potential vanilloid-1 (TRPV1) receptor has been implicated in the development of epileptic seizures. We examined the effect of the TRPV1 agonist capsaicin on epileptic seizures, neuronal injury and oxidative stress in a model of status epilepticus induced in the rat by intraperitoneal (i.p.) injections of pentylenetetrazole (PTZ). Capsaicin was i.p. given at 1 or 2 mg/kg, 30 min before the first PTZ injection. Other groups were i.p. treated with the vehicle or the anti-epileptic drug phenytoin (30 mg/kg) alone or co-administered with capsaicin at 2 mg/kg. Brain levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, and paraoxonase-1 (PON-1) activity, seizure scores, latency time and PTZ dose required to reach status epilepticus were determined. Histopathological assessment of neuronal damage was done. Results showed that brain MDA decreased by treatment with capsaicin, phenytoin or capsaicin/phenytoin. Nitric oxide decreased by capsaicin or capsaicin/phenytoin. GSH and PON-1 activity increased after capsaicin, phenytoin or capsaicin/phenytoin. Mean total seizure score decreased by 48.8% and 66.3% by capsaicin compared with 78.7% for phenytoin and 69.8% for capsaicin/phenytoin treatment. Only phenytoin increased the latency (115.7%) and threshold dose of PTZ (78.3%). Capsaicin did not decrease the anti-convulsive effect of phenytoin but prevented the phenytoin-induced increase in latency time and threshold dose. Neuronal damage decreased by phenytoin or capsaicin at 2 mg/kg but almost completely prevented by capsaicin/phenytoin. Thus in this model of status epilepticus, capsaicin decreased brain oxidative stress, the severity of seizures and neuronal injury and its co-administration with phenytoin afforded neuronal protection.

Effect of fentanyl and its three novel analogues on biochemical, oxidative, histological, and neuroadaptive markers after sub-acute exposure in mice

AimsComparative sub-acute toxicity, including tolerance and dependence potential of fentanyl and its three novel and potent analogues was determined in mice. Main methodsComparative sub-acute (21 d, intraperitoneal; 1/10 LD50) toxicity of fentanyl and its three novel analogues viz., N-(1-(2-phenoxyethyl)-4-piperidinyl) propionanilide (2), N-isopropyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (5), and N-t-butyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (6) was determined in mice. Animals were observed for additional seven days to assess the recovery. The brain, liver and kidney toxicity was assessed on the basis of various biochemical, oxidative, histological, and neuroadaptive markers. The expression levels of key neuronal markers associated with drug tolerance and dependence were investigated by western blot and immunohistochemistry. Key findingsFentanyl and its analogues caused abnormal levels of liver and kidney specific biomarkers in plasma. Brain malondialdehyde (MDA) levels were raised by all the treatments and kidney MDA level by analogue 6 (21 d). Reduced glutathione levels in brain, liver, and kidney were diminished by all the treatments (21 & 28 d) and a significant change in the levels of antioxidant enzymes was also produced mainly after 21 d. The deleterious effects of fentanyl and its analogues were further substantiated by corresponding histopathological changes in brain, liver and kidney (21 & 28 d). These compounds were also found to produce neuroadaptive changes as evidenced by the increased expression levels of c-Fos, glucocorticoid receptor, N-methyl-d-aspartate receptor1 and μ-opioid receptor (21 & 28 d). SignificanceThree novel analogues of fentanyl were envisaged to have alternative therapeutic potentials. However, their comparative sub-acute toxicity revealed undesirable side effects, thereby masking their therapeutic ability.

Observing Malondialdehyde-Mediated Signaling Pathway in Cerebral Ischemia Reperfusion Injury with a Specific Nanolight

Cerebral ischemia reperfusion injury (CIRI) is closely related to lipid peroxidation. Malondialdehyde (MDA), as a biomarker of lipid peroxidation, is prone to addition with biomacromolecules, resulting in a secondary cerebral injury. However, desirable tools for in vivo-determining cerebral MDA are scarce. Thus, we devised innovative polymer carbon dots carbonized by benzoyl hydrazine and named them BH-PCDs. BH-PCDs covered with hydrazine groups directly form from one-pot synthesis. The functional nanoparticle specifically identifies MDA via a photoinduced electron transfer (PET) mechanism from other similar biological species, especially reactive carbonyl species. BH-PCDs afforded several valuable traits of a simple preparation, a large two-photon absorption cross section, and exceptional biocompatibility, as well as the ability of traversing the blood-brain barrier. Relying on BH-PCDs, we real-time portrayed the increased cerebral MDA under CIRI. Furthermore, combining with a commercial indicator of the superoxide anion (O2•-), an O2•--regulated MDA level under CIRI was visualized in vivo. Moreover, we demonstrated MDA inactivated glutamine synthetase under CIRI, mediating the glutamate level. Overall, we provide a perspective nanolight serviceable for treating CIRI, which could reveal the physiopathology mechanism of brain MDA.

Fish Oil and Primrose Oil Suppress the Progression of Alzheimer's Like Disease Induced by Aluminum in Rats.

The role of fish oil, primrose oil and their mixture in ameliorating the changes in Alzheimer's like model was evaluated in rats. Primrose oil and primrose/fish oil mixture fatty acids composition was assessed by gas chromatography. The rat experiment consisted of 5 groups; the first fed on balanced diet as control normal (CN); the other four groups treated with intraperitoneal aluminum lactate and consumed dyslipidemic diet; one group served as control Alzheimer's like disease (CA) while the other three groups (test groups) received daily oral dose from primrose oil, fish oil and primrose/fish oil mixture separately for 5 weeks. Results showed primrose oil and primrose/ fish oil mixture to contain gamma linolenic acid as 9.15 and 4.3% of total fatty acids, respectively. Eicosapentaenoic and docosahexaenoic were present as 10.9 and 6.5 %, respectively in the oil mixture. Dyslipidemia and increased erythrocyte sedimentation rate (ESR), plasma butyrylcholinesterase (BChE), brain malondialdehyde (MDA) and NO with decrease in plasma magnesium, brain catalase, reduced glutathione, body weight gain and brain weight were demonstrated in CA compared to CN. Brain histopathology and immuno-histochemistry showed neuronal degeneration and neurofibrillary tangles with elevated myeloperoxidase and nuclear factor-kappa B in CA compared to CN. The tested oils demonstrated neuro-protection reflected in the variable significant improvement of biochemical parameters, immuno-histochemistry and brain histopathology. Primrose/fish oil mixture was superior in reducing ESR, brain MDA, plasma activity of BChE and brain histopathological changes along with elevating plasma magnesium. Primrose/fish oil mixture and fish oil were more promising in improving plasma high density lipoprotein cholesterol (HDL-C) than primrose. Fish oil was the most efficient in improving plasma total cholesterol (T-C), low density lipoprotein cholesterol and T-C /HDL-C. Primrose/fish oil mixture and primrose oil were superior in elevating brain catalase compared to fish oil. Other parameters were equally improved by the different oil treatments. Primrose oil, fish oil and their mixture reduced the progression of Alzheimer's disease in rats with superiority to primrose/fish oil mixture.

Electromagnetic Waves from Mobile Phones may Affect Rat Brain During Development.

To investigate the effects of electromagnetic waves (EMWs) from mobile phones (MPs) on rat brains of rats by morphological and biochemical analysis. EMW was applied for two hours/day until birth in stand-by fetal and EMW fetal groups and postnatal 60 < sup > th < /sup > day in stand-by and EMW groups. The control group was not exposed to MP. On postnatal 60 < sup > th < /sup > day, brain malondialdehyde (MDA) and glutathione (GSH) levels were measured, and western blot analysis was performed to determine glial fibrillary acidic protein (GFAP) content. Hematoxylin and eosin staining and GFAP immunohistochemistry were applied. Trigeminal nerves were examined using the transmission electron microscope. In comparison to controls, rats exposed to MP in stand-by or talk modes had significantly increased neuronal damage in the cortex and hippocampus. Increased MDA levels in the EMW group and decreased GSH levels in the stand-by, EMW fetal and EMW groups were found compared with controls. Increased GFAP content in the EMW group and increased GFAP staining in the EMW fetal and EMW groups compared to controls were observed. EMW group had a significantly decreased number of myelinated axons than control animals. The results of this study suggests that 1800 MHz EMWs (SAR=1.79 W/kg) exposure in the prenatal and early postnatal life may lead to trigeminal nerve damage in addition to oxidative stress-induced neuronal degeneration and astroglial activation in the rat brain. Effects seem to be mode related, being more detrimental in groups exposed to MP during talk mode.

Protective Effects of Adrenomedullin on Rat Cerebral Tissue After Transient Bilateral Common Carotid Artery Occlusion and Reperfusion.

ObjectiveWe aimed to investigate the protective effect of adrenomedullin (ADM) on cerebral tissue of rats with cerebral ischemia/reperfusion (I/R) injury.MethodsThirty-two Wistar rats were randomized into four groups (n=8). In the I/R Group, bilateral common carotid arteries were clamped for 30 minutes and, subsequently, reperfused for 120 minutes. In the ADM Group, rats received 12 µg/kg of ADM. In the I/R+ADM Group, bilateral common carotid arteries were clamped for 30 minutes and, subsequently, the rats received 12 µg/ kg of ADM. Then, reperfusion was performed for 120 minutes. The Control Group underwent no procedure. Blood and brain tissue samples were collected for biochemical and histopathological analysis. Serum malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were analysed. Brain tissue was evaluated histopathologically and neuronal cells were counted in five different fields, at a magnification of ×400.ResultsBrain MDA in I/R Group was significantly higher than in ADM Group. Brain GPx and SOD in I/R+ADM Group were significantly higher than in I/R Group. The number of neurons was decreased in I/R Group compared to the Control Group. The number of neurons in I/R+ADM Group was significantly higher than in I/R Group, and lower than in Control Group. Apoptotic changes decreased significantly in I/R+ADM Group and the cell structure was similar in morphology compared to the Control Group.ConclusionWe demonstrated the cerebral protective effect of ADM in the rat model of cerebral I/R injury after bilateral carotid artery occlusion.