Brain Lipid Peroxidation Research Articles

Ten gigahertz microwave radiation impairs spatial memory, enzymes activity, and histopathology of developing mice brain.

For decades, there has been an increasing concern about the potential hazards of non-ionizing electromagnetic fields that are present in the environment and alarming as a major pollutant or electro-pollutant for health risk and neuronal diseases. Therefore, the objective of the present study was to explore the effects of 10GHz microwave radiation on developing mice brain. Two weeks old mice were selected and divided into two groups (i) sham-exposed and (ii) microwave-exposed groups. Animals were exposed for 2h/day for 15 consecutive days. After the completion of exposure, within an hour, half of the animals were autopsied immediately and others were allowed to attain 6weeks of age for the follow-up study. Thereafter results were recorded in terms of various biochemical, behavioral, and histopathological parameters. Body weight result showed significant changes immediately after treatment, whereas non-significant changes were observed in mice attaining 6weeks of age. Several other endpoints like brain weight, lipid peroxidation, glutathione, protein, catalase, and superoxide dismutase were also found significantly (p<0.05) altered in mice whole brain. These significant differences were found immediately after exposure and also in follow-up on attaining 6weeks of age in microwave exposure group. Moreover, statistically significant (p<0.001) effect was investigated in spatial memory of the animals, in learning to locate the position of platform in Morris water maze test. Although in probe trial test, sham-exposed animals spent more time in searching for platform into the target quadrant than in opposite or other quadrants. Significant alteration in histopathological parameters (qualitative and quantitative) was also observed in CA1 region of the hippocampus, cerebral cortex, and ansiform lobule of cerebellum. Results from the present study concludes that the brain of 2weeks aged mice was very sensitive to microwave exposure as observed immediately after exposure and during follow-up study at 6weeks of age.

Bougainvillea spectabilis flowers extract protects against the rotenone-induced toxicity.

To investigate the effect of two extracts of Bougainvillea spectabilis (B. spectabilis) flowers with yellow and pink/purple on brain oxidative stress and neuronal damage caused in rats by systemic rotenone injection. Rotenone 1.5mg/kg was given three times per week alone or in combination with B. spectabilis flowers extracts (25mg or 50mg) via the subcutaneous route for 2 weeks. Brain concentrations of the lipid peroxidation marker malondialdehyde (MDA), reduced glutathione, nitric oxide (nitrite), the pro-inflammatory cytokine interleukin-1beta (Il-1β) as well as butyrylcholinesterase, and paraoxonase-1 (PON-1) activities, were determined. Histopathology and caspase-3 immunohistochemistry were also performed. Rotenone resulted in significant increases of brain MDA (the product of lipid peroxidation), and nitric oxide content along with decreased brain reduced glutathione. There were also marked and significant inhibition of brain PON-1 and BChE activities and increased Il-1β in brain of rotenone-treated rats. B. spectabilis flowers extract itself resulted in brain oxidative stress increasing both lipid peroxidation and nitrite content whilst inhibiting PON-1 activity. The yellow flowers extract inhibited BChE activity and increased brain Il-1β. When given to rotenone-treated rats, B. spectabilis extracts, however, decreased lipid peroxidation while their low administered doses increased brain GSH. Brain nitrite decreased by the pink extract but showed further increase by the yellow extract. Either extract, however, caused further inhibition of PON-1 activity while the yellow extract resulted in further inhibition of BChE activity. Histopathological studies indicated that both extracts protected against brain, liver and kidney damage caused by the toxicant. These data indicate that B. spectabilis flowers extracts exert protective effect against the toxic effects of rotenone on brain, liver and kidney. B. spectabilis flowers extracts decreased brain lipid peroxidation and prevented neuronal death due to rotenone and might thus prove the value in treatment of Parkinson's disease.

Nicorandil reverses the behavioral changes and brain oxidative stress in a model of schizophrenia induced by ketamine in mice

We examined the effect of the KATP channel opener nicorandil and the KATP channel blocker glibenclamide on the behavioral and biochemical responses to ketamine in mice. Ketamine was injected at 30 mg/kg intraperitoneally (i.p.) daily for 2 weeks, and mice were then treated with either saline, glibenclamide (5 mg/kg), nicorandil (1 or 5 mg/kg), sucrose 1 g/kg, or glibenclamide + sucrose 1 g/kg, i.p. daily for another 8 days. The control group received only saline. Data indicated that (i) ketamine increased locomotion, rearing, and grooming behaviors. Locomotor activity increased in the center while rearing activity increased in the periphery and center of the open field. Social interaction was markedly decreased by ketamine. Nicorandil at 1 mg/kg increased and at 5 mg/kg produced marked depression in ambulation in the center of the field and in rearing in the field periphery. Locomotor activity and rearing of ketamine-treated mice were not affected by glibenclamide. Meanwhile, either agent reversed the increase in grooming and the inhibition of social interaction caused by ketamine. Sucrose had no significant effect on grooming or social interaction of mice given ketamine but increased ambulation and rearing activity in the field center. (ii) Ketamine caused a significantly elevated brain lipid peroxidation (malondialdehyde) while decreasing reduced glutathione, nitric oxide, and paraoxonase-1 activity. These biochemical alterations were markedly alleviated by nicorandil or glibenclamide. The study suggests a potential therapeutic value for the KATP channel opener nicorandil in the ketamine model of schizophrenia.

Energy Drink Induced Lipid Peroxidation and Oxidative Damage in Rat Liver and Brain When Used Alone or Combined with Alcohol.

Energy drinks (ED) are containing large doses of metabolic stimulants and its use with ethanol has increased dramatically among young adults. In this study, we examined the effects of ED exposure either alone or in combination with ethanol on oxidative stress parameters including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and lipid peroxidation parameter malondialdehyde (MDA) in rat. Some histopathological findings were also evaluated. ED exposure led to a dose-dependent increase in liver MDA compared to the control indicating oxidative damage. Histopathological findings also revealed that ED alone may generate liver damage. Ethanol exposure increased MDA level and SOD, CAT, and GSH-Px activity in both the brain and the liver. The combination of ethanol and ED produced greater damage which is considered by further increases in SOD and GSH-Px activity in the brain. Similar results for MDA were observed in both the liver and brain as well. Our findings suggest that ED consumption alone or combination with ethanol may represent a significant public health concern.

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.

Abstract WP96: The Histone Deacetylase Inhibitor, Sodium Butyrate, Exhibits Biphasic Neuroprotective Mechanisms in the Acute Phase of Ischemic Stroke in Middle-Aged Female Rats

Introduction: Sodium butyrate (NaB) is a histone deacetylase (HDAC) inhibitor exhibiting anti-inflammatory and neuroprotective effects in a rat ischemic model of a myocardial ischemia as well as stroke. Although clinical evidence shows that older women are at higher risk for stroke occurrence and greater stroke severity, no studies have evaluated the effectiveness of NaB either in females or in older animals. Methods: To determine the effects of NaB on stroke in older females, acyclic middle-aged Sprague-Dawley female rats (10-12 months old, constant diestrus) were subject to middle cerebral artery occlusion (MCAo) by intracerebral injection of recombinant endothelin-1. Rats were treated with NaB (300 mg/kg, i.p.) at 6h and 30h following ET-1 injection. Animals were tested for sensory motor performance pre and post stroke. Subsequently, rats were sacrificed at the early (2d) or late (5d) acute phase after MCAo. Serum and tissue samples were collected for biochemical analyses. Results: NaB treatment reduced infarct volume and ameliorated stroke-induced sensory motor impairment in middle-aged female rats post MCAo. At the early acute phase, NaB treatment decreased brain lipid peroxides, and reduced serum levels of GFAP, a marker of blood brain barrier permeability. NaB also reduced expression of the inflammatory cytokine IL-1beta in circulation and IL-18 in the ischemic hemisphere. At the late acute phase, NaB treatment further suppressed MCAo-induced increase of IL-1beta, IL-17A, and IL-18 in brain lysates (cortex and striatum) from the ischemic hemisphere, and decreased ischemia-induced upregulation of IL-1beta and IL-18 in circulation, indicating a potent anti-inflammatory effect of the HDAC inhibitor. Moreover, NaB treatment also increased expression of IGF-1, a known neuroprotectant, in peripheral tissues including serum, liver, and spleen. Conclusions: These data provide the first evidence that delayed (&gt; 6h) NaB treatment post-stroke is neuroprotective in older female rats. Importantly, these data also show that in addition to its well-known anti-inflammatory actions, NaB may exert a biphasic effect after stroke, operating initially to reduce oxidative stress in the brain, and later, elevating IGF-1 expression in peripheral tissues.

Quercetin Improves Neurobehavioral Performance Through Restoration of Brain Antioxidant Status and Acetylcholinesterase Activity in Manganese-Treated Rats.

The present study investigated the neuroprotective mechanism of quercetin by assessing the biochemical and behavioral characteristics in rats sub-chronically treated with manganese alone at 15mg/kg body weight or orally co-treated with quercetin at 10 and 20mg/kg body weight for 45 consecutive days. Locomotor behavior was monitored using video-tracking software during a 10-min trial in a novel environment whereas the brain regions namely the hypothalamus, cerebrum and cerebellum of the rats were processed for biochemical analyses. Results indicated that co-treatment with quercetin significantly (p < 0.05) prevented manganese-induced locomotor and motor deficits specifically the decrease in total distance travelled, total body rotation, maximum speed, absolute turn angle as well as the increase in time of immobility and grooming. The improvement in the neurobehavioral performance of manganese-treated rats following quercetin co-treatment was confirmed by track and occupancy plot analyses. Moreover, quercetin assuaged manganese-induced decrease in antioxidant enzymes activities and the increase in acetylcholinesterase activity, hydrogen peroxide generation and lipid peroxidation levels in the hypothalamus, cerebrum and cerebellum of the rats. Taken together, quercetin mechanisms of ameliorating manganese-induced neurotoxicity is associated with restoration of acetylcholinesterase activity, augmentation of redox status and inhibition of lipid peroxidation in brain of rats.

Assessment of the in vitro anti-lipid peroxidative activity of Costus afer stem extract

Objective: Costus afer is a perennial monocot consumed as a remedy for various ailments. The present study investigates the effect of Costus afer stem extract on ferrous/ascorbate-induced lipid peroxidation in rat brain, liver and kidney homogenates. The inherent antioxidant and free radical scavenging potentials of the extract were also assessed using various in-vitro models. Methods: Homogenates of isolated tissues were prepared and lipid peroxidation was induced using the ferrous/ascorbate system and subsequently incubated with various concentrations of the extract. The ability of the methanolic extract to scavenge hydroxyl radicals, hydrogen peroxide and its ability to reduce ferric ions were investigated. The total antioxidant potential via the phosphomolybdate method was also measured. Results: The results revealed that Costus afer stem extract reduced tissue lipid peroxidation induced by ferrous/ascorbate. The extract also possessed significant antioxidant/free radical scavenging activity via the other in vitro models. In all cases, the effects were concentration-dependent. Conclusion: The methanolic extract of Costus afer stem possessed significant antioxidant potential ascribable to important phytochemicals and could protect cells/tissues from reactive oxygen species-induced damage. Thus the plant has high pharmacological and ethnobotanical prospects.

Protective Effect of Pluchea lanceolata against Aluminum Chloride-induced Neurotoxicity in Swiss Albino Mice.

Background:Aluminum chloride (AlCl3) is a known potent environmental neurotoxin causing progressive neurodegenerative changes in the brain. The herb Pluchea lanceolata is commonly known as “Rasana” and used as a nerve tonic in neuroinflammatory conditions in Indian system of medicine.Objective:To evaluate the neuroprotective activity of hydroalcoholic extract of P. lanceolata in chronic AlCl3-induced neurotoxicity in Swiss albino mice.Materials and Methods:Albino mice were categorized into four different groups; Group 1served as vehicle control, Group 2 mice were administered with AlCl3, 40 mg/kg body weight by intraperitoneal route for 45 consecutive days. Groups 3 and 4 mice were administered with AlCl3, 40 mg/kg body weight intraperitoneal for 45 consecutive days along with hydroalcoholic extract of P. lanceolata at 200 and 400 mg/kg body weight.Results:Chronic administration of AlCl3 resulted in behavioral deficits, triggered lipid peroxidation, increased acetylcholinesterase (AChE) activity, and histological alterations. Co-administration of hydroalcoholic extract of P. lanceolata attenuated many of the AlCl3-induced alterations such as behavioral, lipid peroxidation, AChE, and histological changes of brain tissue.Conclusion:The results of the present study have demonstrated the protective role of hydroalcoholic extract of P. lanceolata against AlCl3-induced neurotoxicity in Swiss albino mice. The neuroprotective efficacy of P. lanceolata can help reduce the symptoms caused by toxic protein aggregates in several degenerative diseases.SUMMARY The hydro alcoholic extract of Pluchea lanceolata showed neuroprotective activity in albino mice against AlCl3 toxicityThe benefits of Pluchea lanceolata against AlCl3 toxicity includes reduced lipid peroxidation and acetylcholine esterase activity with improved behavioral functionsThe hydro alcoholic extract of Pluchea lanceolata rendered protection against AlCl3 in forebrain, midbrain, cerebellum and hippocampusTherefore Pluchea lanceolata holds pharmacological potentials for treating diseases associated with neuronal toxicity. Abbreviations used: HAPL: Hydro alcoholic extract of Pluchea lanceolata; CAT: Catalase; GSH-Px: Glutathione peroxidase; SOD: Superoxide dismutase; TBARS: Thio-barbituric acid reactive substances; MDA: Malondialdehyde; AChE: Acetylcholine esterase; AOT: Acute oral toxicity; CNS: Central nervous system; H2O2: Hydrogen peroxide; ML: molecular layer; GL: granular layer; MC: microcytic changes; BV: blood vessels; DG: dentate gyrus; PC: pyramidal cells; LD: Lethal dose; ANOVA: Analysis of variance; SEM: Standard error of mean; PCL: Pyramidal cell layer; OCL: Outer granular layer; BV: blood vessels; PM: Pia mater.

Dennettia tripetala seeds inhibit ferrous sulphate-induced oxidative stress in rat tissues in vitro

Objectives: This study was designed to investigate the antioxidant activity of pepper fruit (Dennettia tripetala) seed extract. Methods: Phenol content, reducing activity, Fe(II)-chelating ability and 1,1-diphenyl-2 picryl hydrazyl (DPPH) radical-scavenging ability of the extract were consequently examined whereas the antioxidant potentials and inhibitory effect of D.tripetala seed on FeSO4-induced oxidative stress in some rat tissues were evaluated. Results: The seed had a high concentration of total phenol. Incubation of the liver and brain tissue homogenates in the presence of Fe2+ caused a major increase in the malondialdehyde (MDA) contents of the homogenates. However, the aqueous seed extract of D.tripetala caused a significant decrease in the MDA contents of the liver and brain in a dose-dependent manner. The aqueous extract of the seed had a considerably higher inhibitory effect on Fe2+-induced lipid peroxidation in the rat brain than the liver homogenates. Conclusion: The high inhibitory effect of Dennettia tripetala seed is attributable to its high phytochemical content, Fe2+ chelating ability, DPPH scavenging ability and reducing power. These results suggest that the seed extract of D.tripetala possess body antioxidant pool improving potentials which may contribute to the prevention of the incidence of neurodegenerative maladies.

Different doses of dexmedetomidine reduce plasma cytokine production, brain oxidative injury, PARP and caspase expression levels but increase liver oxidative toxicity in cerebral ischemia-induced rats.

Cerebral ischemia-induced progression of brain, liver, and erythrocyte oxidative injuries might be modulated by dexmedetomidine (DEX) as a potent antioxidant and anti-inflammatory drug. The present study was conducted to explore whether two different doses of DEX protect against plasma cytokine and brain, liver and erythrocyte oxidative toxicity and apoptosis in cerebral ischemia-induced rats. Forty-two rats were equally divided into 7 groups. The first and second groups were used as untreated and sham controls, respectively. The third (DEX4) and fourth (DEX40) groups received 4mg/kg and 40mg/kg DEX treatments. The fifth, sixth and seventh group were operated on to induce cerebral ischemia. The fifth, sixth and seventh groups are used to represent cerebral ischemia, cerebral ischemia+DEX4, and cerebral ischemia+DEX40, respectively. DEX was intraperitoneally given to the DEX groups at the 3rd, 24th and 48th hour. Brain and erythrocyte lipid peroxidation (MDA) levels and plasma IL-1β and TNF-α levels were high in the cerebral ischemia group although they were low in the DEX4 and DEX40 groups. Decreased glutathione peroxidase (GSH-Px) and reduced glutathione (GSH) values in the brain and erythrocyte of the cerebral ischemia group were increased by the DEX treatments, although PARP, and the caspase 3 and 9 expressions in the brain were further decreased. Conversely, the cerebral ischemia-induced decrease in the liver vitamin A, vitamin E, GSH, and GSH-Px were further decreased by the DEX treatments, although MDA level, PARP, and caspase 3 and 9 expressions were further increased by the DEX treatments. In conclusion, DEX induced protective effects against cerebral ischemia-induced brain and erythrocyte oxidative injuries through regulation of the antioxidant level and cytokine production. However, both doses of DEX induced oxidative toxicity and apoptotic effects in the rats' livers.

Toxicity of Fe3O4 nanoparticles on oxidative stress status, stromal enzymes and mitochondrial respiration and swelling of Oryctolagus cuniculus brain cortex

Fe3O4 nanoparticles are the most widely used metal oxide nanoparticles especially, in biomedical applications. Although, nanoparticles can enter to the different organs, little is known so far on the neurotoxic potential and oxidative stress of Fe3O4. Here the understanding of the effect of Fe3O4 nanoparticles on the general Redox state of rabbit brain and the effect on mitochondrial swelling and respiration were assessed. Fe3O4 resulted in increase of brain markers, lipid peroxidation, protein and ROS formation. Mitochondrial enzymes and swelling were elevated with decreased respiration level. Caspase 3 activity and TNF-α level were also increased. Finally, our study suggested that the mitochondrial disease and dysfunction with elevated oxidative stress in rabbit brain treated with 200 and 300 μg/kg per Os is the original of neurotoxicity and maybe the original cause of neurodegenerative disease.

The histone deacetylase inhibitor, sodium butyrate, exhibits neuroprotective effects for ischemic stroke in middle-aged female rats

BackgroundSodium butyrate (NaB) is a histone deacetylase (HDAC) inhibitor exhibiting anti-inflammatory and neuroprotective effects in a rat ischemic model of stroke as well as a myocardial ischemia model. Although clinical evidence shows that older women are at higher risk for stroke occurrence and greater stroke severity, no studies have evaluated the effectiveness of NaB either in females or in older animals.MethodsTo determine the effects of NaB on stroke in older females, acyclic middle-aged Sprague-Dawley female rats (9–11 months old, constant diestrus) were subject to middle cerebral artery occlusion (MCAo) by intracerebral injection of recombinant endothelin-1. Rats were treated with NaB (300 mg/kg, i.p.) at 6 and 30 h following ET-1 injection. Animals were sacrificed at the early (2 days) or late (5 days) acute phase after MCAo. Serum and tissue lysates were collected for biochemical analyses.ResultsNaB treatment reduced infarct volume and ameliorated sensory motor impairment in middle-aged female rats, when measured at 2 and 5 days post MCAo. At the early acute phase (2 days post stroke), NaB treatment decreased brain lipid peroxides, and reduced serum levels of GFAP, a surrogate marker of blood-brain barrier (BBB) permeability. NaB also reduced expression of the inflammatory cytokine IL-1beta in circulation and IL-18 in the ischemic hemisphere. At the late acute phase (5 days post stroke), NaB treatment further suppressed MCAo-induced increase of IL-1beta, IL-17A, and IL-18 in brain lysates (cortex and striatum) from the ischemic hemisphere, and decreased ischemia-induced upregulation of IL-1beta and IL-18 in circulation, indicating a potent anti-inflammatory effect of the HDAC inhibitor. Moreover, NaB treatment also increased expression of IGF-1, a known neuroprotectant, in peripheral tissue including serum, liver, and spleen at the late acute phase.ConclusionsThese data provide the first evidence that delayed (>6 h) NaB treatment post-stroke is neuroprotective in older female rats. Additionally, these data also show that in addition to its well-known anti-inflammatory actions, NaB may exert a biphasic effect after stroke, operating initially to reduce BBB permeability and oxidative stress in the brain, and later, elevating IGF-1 expression in peripheral tissues.

Novel neuroprotective and hepatoprotective effects of citric acid in acute malathion intoxication.

To study the effect of citric acid given alone or combined with atropine on brain oxidative stress, neuronal injury, liver damage, and DNA damage of peripheral blood lymphocytes induced in the rat by acute malathion exposure. Rats were received intraperitoneal (i.p.) injection of malathion 150mg/kg along with citric acid (200 or 400mg/kg, orally), atropine (1mg/kg, i.p.) or citric acid 200mg/kg+atropine 1mg/kg and euthanized 4h later. Malathion resulted in increased lipid peroxidation (malondialdehyde) and nitric oxide concentrations accompanied with a decrease in brain reduced glutathione, glutathione peroxidase (GPx) activity, total antioxidant capacity (TAC) and glucose concentrations. Paraoxonase-1, acetylcholinesterase (AChE) and butyrylcholinesterase activities decreased in brain as well. Liver aspartate aminotransferase and alanine aminotransferase activities were raised. The comet assay showed increased DNA damage of peripheral blood lymphocytes. Histological damage and increased expression of inducible nitric oxide synthase (iNOS) were observed in brain and liver. Citric acid resulted in decreased brain lipid peroxidation and nitric oxide. Meanwhile, glutathione, GPx activity, TAC capacity and brain glucose level increased. Brain AChE increased but PON1 and butyrylcholinesterase activities decreased by citric acid. Liver enzymes, the percentage of damaged blood lymphocytes, histopathological alterations and iNOS expression in brain and liver was decreased by citric acid. Meanwhile, rats treated with atropine showed decreased brain MDA, nitrite but increased GPx activity, TAC, AChE and glucose. The drug also decreased DNA damage of peripheral blood lymphocytes, histopathological alterations and iNOS expression in brain and liver. The study demonstrates a beneficial effect for citric acid upon brain oxidative stress, neuronal injury, liver and DNA damage due to acute malathion exposure.

Statins prevent cognitive impairment after sepsis by reverting neuroinflammation, and microcirculatory/endothelial dysfunction

Acute brain dysfunction is a frequent condition in sepsis patients and is associated with increased mortality and long-term neurocognitive consequences. Impaired memory and executive function are common findings in sepsis survivors. Although neuroinflammation and blood-brain barrier dysfunction have been associated with acute brain dysfunction and its consequences, no specific treatments are available that prevent cognitive impairment after sepsis. Experimental sepsis was induced in Swiss Webster mice by intraperitoneal injection of cecal material (5mg/kg, 500μL). Control groups (n=5/group each experiment) received 500μL of saline. Support therapy recover (saline 0.9%, 1mL and imipenem 30mg/kg) were applied (6, 24 and 48h post injection, n=5–10/group, each experiment), together or not with additive orally treatment with statins (atorvastatin/simvastatin 20mg/kg b.w.). Survival rate was monitored at 6, 24 and 48h. In a setting of experiments, animals were euthanized at 6 and 24h after induction for biochemical, immunohistochemistry and intravital analysis. Statins did not prevented mortality in septic mice, however survivors presented lower clinical score. At another setting of experiments, after 15days, mice survivors from fecal supernatant peritoneal sepsis presented cognitive dysfunction for contextual hippocampal and aversive amygdala-dependent memories, which was prevented by atorvastatin/simvastatin treatment. Systemic and brain tissue levels of proinflammatory cytokines/chemokines and activation of microglial were lower in septic mice treated with statins. Brain lipid peroxidation and myeloperoxidase levels were also reduced by statins treatment. Intravital examination of the brain vessels of septic animals revealed decreased functional capillary density and increased rolling and adhesion of leukocytes, and blood flow impairment, which were reversed by treatment with statins. In addition, treatment with statins restored the cholinergic vasodilator response due to sepsis. Taken together, these data demonstrated that statins reverse microvascular dysfunction and reduce neuroinflammation during sepsis, preventing the development of long-term cognitive decline.

Cytotoxic and antioxidative potentials of ethanolic extract of Eugenia uniflora L. (Myrtaceae) leaves on human blood cells.

Eugenia uniflora is used in the Brazilian folk medicine to treat intestinal disorders and hypertension. However, scanty information exist on its potential toxicity to human, and little is known on its antioxidant activity in biological system. Hence, we investigated for the first time the potential toxic effects of ethanolic extract (EtOH) of E. uniflora (EEEU) in human leukocytes and erythrocytes, as well as its influence on membrane erythrocytes osmotic fragility. In addition, EEEU was chemically characterized and its antioxidant capacity was evaluated. We found that EEEU (1-480μg/mL) caused neither cytotoxicity nor DNA damage evaluated by Trypan blue and Comet assay, respectively. EEEU (1-480μg/mL) did not have any effect on membrane erythrocytes fragility. In addition, EEEU inhibited Fe2+-induced lipid peroxidation in rat brain and liver homogenates, and scavenged the DPPH radical. EEEU presented some polyphenolic compounds with high content such as quercetin, quercitrin, isoquercitrin, luteolin and ellagic acid, which may be at least in part responsible for its beneficial effects. Our results suggest that consumption of EEEU at relatively higher concentrations may not result in toxicity. However, further in vitro and in vivo studies should be conducted to ascertain its safety.

Hesperidin, a citrus flavonoid, protects against l-methionine-induced hyperhomocysteinemia by abrogation of oxidative stress, endothelial dysfunction and neurotoxicity in Wistar rats

Context: Hesperidin (HSP), a flavanoglycone found in citrus fruits, has antioxidant, anti-inflammatory and neuroprotective properties.Objective: This study evaluates the protective effect of HSP on l-methionine-induced hyperhomocysteinemia (HHcy) in rats.Materials and methods: Male Wistar rats were randomly divided into seven groups as DMSO, l-methionine, HSP (25, 50 and 100 mg/kg), HSP-per se (100 mg/kg) and donepezil (0.1 mg/kg). HHcy was induced by oral administration of l-methionine (1.7 g/kg) for 32 days. From the 14th day of study HSP (25, 50 and 100 mg/kg) and donepezil was administered orally to l-methionine-treated rats. Cognitive impairment induced by HHcy was determined using the Morris water maze (MWM) and Y-maze on video tracking system (28th–32nd day). Different biomarkers of HHcy in serum and brain and vascular reactivity were evaluated and histopathology (thoracic aorta and brain) was done.Results: HSP (100 mg/kg) treatment in l-methionine-treated rats exhibited significant (p < 0.001) dose-dependent activity and reduced behavioural deficits, brain acetylcholinesterase (25.99 ± 2.36 versus 10.73 ± 1.26 μmoles/mg), brain lipid peroxidation (15.25 ± 1.65 versus 6.18 ± 0.74 nM/mg), serum homocysteine (Hcy) (22.37 ± 0.30 versus 11.01 ± 1.01 μg/mL) and serum cholesterol (182.7 ± 2.15 versus 101.5 ± 2.76 mg/dL) and increased brain antioxidant levels. HSP significantly (p < 0.001) reduced endothelial dysfunction (ED) by abolishing the effect of l-methionine on acetylcholine-induced endothelial-dependent relaxation and increased serum nitrite and vascular nitric oxide bioavailability along with the restoration of histological aberrations.Conclusion: HSP exerts a protective effect on HHcy by abrogating oxidative stress, ED and neurotoxicity.

Selenium attenuates apoptosis, inflammation and oxidative stress in the blood and brain of aged rats with scopolamine-induced dementia.

A potent antioxidant, selenium might modulate dementia-induced progression of brain and blood oxidative and apoptotic injuries. The present study explores whether selenium protects against experimental dementia (scopolamine, SCOP)-induced brain, and blood oxidative stress, apoptosis levels, and cytokine production in rats. Thirty-two rats were equally divided into four groups. The first group was used as an untreated control. The second group was treated with SCOP to induce dementia. The third and fourth groups received 1.5mg/kg selenium (sodium selenite) and SCOP+selenium, respectively. Dementia was induced in the second and forth groups by intraperitoneal SCOP (1mg/kg) administration. Brain, plasma, and erythrocyte lipid peroxidation levels as well as plasma TNF-α, interleukin (IL)-1β, and IL-4 levels were high in the SCOP group though they were low in selenium treatments. Selenium and selenium+SCOP treatments increased the lowered glutathione peroxidase activity, reduced glutathione, vitamins A and E concentrations in the brain, erythrocytes and plasma of the SCOP group. Apoptotic value expressions as active caspase-3, procaspase-9, and PARP were also increased by SCOP, while they were decreased by selenium and selenium+SCOP treatments. In conclusion, selenium induced protective effects against experimental dementia-induced brain, and blood oxidative injuries and apoptosis through regulation of cytokine production, vitamin E, glutathione concentrations, and glutathione peroxidase activity.

&lt;i&gt;In vitro&lt;/i&gt; evaluation of inhibitory effect of &lt;i&gt;Phoenix dactylifera&lt;/i&gt; bark extract on rat lipid peroxidation and blood hemolysis

Purpose: To determine the polyphenolic content of P. dactylifera L. (date palm) bark extract and to investigate its in vitro inhibitory effects on lipid peroxidation in the brain, liver, and kidney tissues of rat, as well as on blood hemolysis in rats. Methods: P. dactylifera L. barks were collected from Ahvaz, (Khuzestan, Iran). Methanolic extract of the P. dactylifera barks were prepared using maceration method. Total phenolic, flavonoid and proanthocyanidin contents were determined by colorimetric methods. The effects of the extract were investigated on thiobarbituric acid reactive substances formation in Fe 2+ /ascorbate induced-lipid peroxidation in brain, liver and kidney tissues of rats. Furthermore, the inhibitory effects of the extracts on erythrocyte hemolysis caused by 2,2'-Azobis (2-amidinopropane) dihydrochloride (AAPH) were evaluated. Results: Total phenolic, flavonoids and proanthocyanidins contents per each g dry extract of P. dactylifera L. were 50.7 mg tannic acid, 10.38 mg rutin, and 5.45 mg cyanidin, respectively, while halfmaximal inhibitory concentration (IC 50 ) for inhibition of lipid peroxidation in brain, liver, and kidney tissues of rats was 3150.71, 1941.45, and 1546.01 μg/mL, respectively, and for the inhibition of erythrocyte hemolysis, it was 472.41 μg/mL. Conclusion: The findings of this study indicate significant anti-lipid peroxidation and anti-hemolytic effects of the bark extract. Therefore, the extract can potentially be used for the in vivo treatment of diseases associated with lipid peroxidation such as cancers and Alzheimer's disease, but further studies are required. Keywords: Phoenix dactylifera , Date palm, Lipid peroxidation, Antioxidant, Erythrocyte hemolysis

In vitro and in silico antioxidant and toxicological activities of Achyrocline satureioides

Ethnopharmacological relevanceAchyrocline satureioides (“macela or marcela”) is a medicinal plant, traditionally collected in “Good Friday” before sunrise. In traditional medicine, dried flowers of A. satureioides are used as anti-dyspeptic, antispasmodic and anti-inflammatory. Aim of the studyTo evaluate the phytochemical profile and to present an in vitro and in silico approach about toxicity and antioxidant potential of A. satureioides flowers extract and its major phytoconstituents. Materials and methodsPlant were collected according to the popular tradition. Extract were obtained by infusion and analyzed from high-performance liquid chromatography. Toxicity was evaluated in Artemia salina and human lymphocytes. Extract antioxidant activity was determined with total antioxidant capacity, DPPH• and ABTS+• scavenging, ferric reducing antioxidant power, deoxyribose degradation assay, and thiobarbituric acid reactive substances (TBA-RS) assay. TBA-RS inhibitions were evaluated in brain of rats for A. satureioides extract and its major phytoconstituents. Predictions of activity spectra for substances and in silico toxicity evaluation from major phytoconstituents were performed via computer simulation. ResultsChromatographic data indicated isoquercitrin, quercetin and caffeic acid as main compounds in flowers extract. Toxicity tests demonstrated a very low toxic potential of A. satureioides. Extract exhibited antioxidant activities in low concentrations. Both extract and major phytochemicals standards showed protection against lipid peroxidation in brain of rats. Computer simulations pointed some biological activities in agreement with traditional use, as well as some experimental results found in this work. Moreover, in silico toxic predictions showed that the A. satureioides major compounds had low probability for toxic risk. ConclusionOur results indicate that A. satureioides infusion possesses low toxicological potential and an effective antioxidant activity. These findings confirm the traditional use of this plant in the folk medicine.