Brain Lipid Peroxidation Research Articles

Fagopyrum tataricum (L.) Gaertn interacts with Gsk-3β/Nrf-2 signalling to protect neurotoxicity in a zebrafish model

Ethnopharmacological relevanceFagopyrum tataricum (L.) Gaertn is used as a folk medicine in many Asian countries due to its anti-inflammatory, antioxidant, and several other health-promoting properties. It is also prescribed to improve neurocognitive functions and alleviate inflammatory conditions. Aim of the studyOxidative stress and neuroinflammation plays a crucial role in neurodegenerative conditions. Hence, based on the ethnomedical claims and available literature, the present study investigated neuroprotective efficacy of a seed extract (ft-ext) of Fagopyrum tataricum against acrylamide (ACR)-induced neurotoxicity. Materials and methodsThe phytochemical characterization of ft-ext was performed by a high-performance liquid chromatography method. Molecular interactions of the identified compounds of ft-ext were studied using an in-silico docking tool. An in-vitro protein denaturation assay was done to check anti-inflammatory activity. The 5 days’ post-fertilized zebrafish larvae were exposed to 1 mM and 2.5 mM ACR with or without ft-ext for 72 h to study its neuroprotective efficacy. Real-time polymerase chain reaction and western blotting studies were performed to analyse the oxidative stress-related gene and protein expressions respectively. ResultsThe extract showed the presence of chlorogenic acid, rutin, caffeic acid, vitexin, syringic acid, quercetin, p-coumaric acid, kaempferol, and ferulic acid. In-vitro protein denaturation assay of ft-ext showed a potent anti-inflammatory effect. The ft-ext improved ACR-mediated locomotor deficit and reduced overall mortality in the larvae. The brain lipid peroxidation and protein carbonylation results revealed an elevated level of oxidative stress in the ACR-treated group, which was reduced in ft-ext-treated larvae. The extract treatment increased the expression of nrf2, gpx, and hmox1a, while simultaneously downregulated trxr2 levels in the brain of larvae exposed to ACR. The treatment also showed inactivation of Gsk-3β, thus maintaining a normal pool of Nrf2 and β-catenin. Molecular docking of identified compounds of ft-ext showed possible hydrogen and hydrophobic interactions with Gsk-3β. ConclusionThe ft-ext prevents ACR-mediated neurotoxicity by suppressing Gsk-3β mediated oxidative stress.

Anticholinesterase and antioxidant activity of Drynaria quercifolia and its ameliorative effect in scopolamine-induced memory impairment in mice

Ethnopharmacological relevanceDrynaria quercifolia is an epiphytic fern distributed all over Bangladesh with traditional use in treating neurological disorders and other ailments. Although several pharmacological activities of D. quercifolia have been investigated, the neuroprotective potential of this plant is still unexplored. Aim of studyIn this study, we evaluated the in vitro anticholinesterase and antioxidant activities of D. quercifolia and the neuroprotective effect in scopolamine-induced memory-impaired mouse model. Materials and methodsThe crude methanol extract (DCM) of the plant was fractionated to prepare n-hexane (DHF), chloroform (DCF), ethyl acetate (DEF), and aqueous (DAF) factions. All the fractions were evaluated for anticholinesterase activity by modified Ellman's method and the antioxidant activity by several in vitro assays such as DPPH and hydroxyl free radicals scavenging, reducing power, and inhibition of brain lipid peroxidation. The effect of the most active fractions (both DCF and DEF) on learning and memory was assessed in scopolamine-induced mouse model of memory-impairment by Morris water maze tasks. Biochemical assays were performed in brain tissue. The active compound was isolated and characterized by chromatographic, spectroscopic, and molecular docking methods. ResultsPhytochemical analysis demonstrated a high content of phenolic and flavonoid in DEF. In vitro studies revealed a strong antioxidant power of DEF and anticholinesterase activity of DCF. Both the DCF and DEF significantly (P˂0.05) reduced the escape latency time in the Morris's water maze tasks, and increased the time spent in the northeast quadrant in the probe trial. Biochemical data demonstrated that treatment with DCF and DEF at different doses significantly (P˂0.0001) inhibited acetylcholinesterase activity, restored GSH levels, and reduced MDA levels in the brain of scopolamine-induced memory-impaired mice, indicating the protective effect of D. quercifolia, possibly by acetylcholinesterase inhibition and oxidative stress prevention. Chromatographic methods of separation led to he isolation of catechin and protocatechuric acid from DEF and 3,4-dihydroxy benzoic acid from DCF. The structure of the compounds was determined by studies of their 1H-NMR spectra. Molecular docking as well as in vitro study suggests the anticholinesterase and antioxidant activity of the isolated compounds. ConclusionOur study suggested that the extracts of D. quercifolia, due to anticholinesterase and antioxidant activity, ameliorate the scopolamine-induced memory impairment in mice and thus may represent therapeutics in the treatment of Alzheimer's disease.

The mechanisms of Huangqi Guizhi Wuwu decoction in treating ischaemic stroke based on network pharmacology and experiment verification

Context Huangqi Guizhi Wuwu Decoction (HGWD) is effective in treating ischaemic stroke (IS). However, its mechanism of action is still unclear. Objective Network pharmacology integrated with in vivo experiments were used to clarify the underlying mechanisms of HGWD for treating IS. Materials and methods TCMSP, GeneCards, OMIM and STRING were used to retrieve and construct visual protein interaction networks for the key targets. The AutoDock tool was used for molecular docking between key targets and active compounds. The neuroprotective effect of HGWD were verified in a middle cerebral artery occlusion (MCAO) model rat. The Sprague-Dawley (SD) rats were divided into sham, model, low-dose (5 g/kg, i.g.), high-dose (20 g/kg, i.g.), and nimodipine (20 mg/kg, i.g.) groups once daily for 7 days. The neurological scores, brain infarct volumes, lipid peroxidation, inflammatory cytokines, Nissl bodies, apoptotic neurons, and signalling pathways were all investigated and evaluated in vivo. Results Network pharmacology identified 117 HGWD targets related to IS and 36 candidate compounds. GO and KEGG analyses showed that HGWD anti-IS effects were mainly associated with PI3K-Akt and HIF-1 signalling pathways. HGWD effectively reduced the cerebral infarct volumes (19.19%), the number of apoptotic neurons (16.78%), and the release of inflammatory cytokines, etc. in MCAO rats. Furthermore, HGWD decreased the levels of HIF-1A, VEGFA, Bax, cleaved caspase-3, p-MAPK1, and p-c-Jun while increasing the expression of p-PI3K, p-AKT1, and Bcl-2. Discussion and conclusion This study initially elucidated the mechanism of HGWD anti-IS, which contributed to the further promotion and secondary development of HGWD in clinical practice.

Lipid peroxidation and neuroinflammation: A possible link between maternal fructose intake and delay of acquisition of neonatal reflexes in Wistar female rats.

Fructose is a common sweetener found in the daily diet supplemented to many processed and ultra-processed foods and beverages. Consumption of fructose-sweetened beverages has drastically increased in the last decades and is widely associated with metabolic disease, systemic pro-inflammatory status, and adverse transgenerational effects. To date, the impact of maternal fructose intake in brain function of the offspring is less explored. Therefore, the aim of this study was first, to investigate adverse effects in developmental milestones of the progeny of mothers with metabolic syndrome (MetS), induced by ad libitum consumption of a 20% fructose solution, and second to identify possible molecular changes in the nervous system of the newborns associated with maternal fructose intake. Wistar rats were randomly separated into two groups with access to water or fructose (20% w/v in water) for 10 weeks. After MetS was confirmed, dams were mated with control males and continued drinking water or fructose solution during gestation. At postnatal day (PN) 1, a subgroup of offspring of each sex was sacrificed and brains were dissected for oxidative stress and inflammatory status analysis. Changes in the developmental milestones due to maternal fructose consumption were studied (PN3-PN21) in another subgroup of offspring. Sexually dimorphic effects were found on the progeny's acquisition of neurodevelopmental milestones, in brain lipid peroxidation, neuroinflammation, and antioxidative defensive response. Our results suggest that dams' MetS, induced by fructose intake, disrupts brain redox homeostasis in female offspring and affects sensorimotor brain circuitry which may have a translational value for studying neurodevelopmental diseases.

Oxidative stress in the pathogenesis of Alzheimer's disease: Improvement of memory-deteriorating disease by administration of plant enzyme

Plant enzymes are natural substances with almost no side effects and reported effects on spatial learning and histopathological alterations of the hippocampus in senescence-accelerated mice. In senescence-accelerated mice (SAMP8), this in vivo study examined the effects of a plant enzyme on the brain hippocampus, memory and spatial cognition. In the Morris water maze, a comparison between the control group of SAMR1 mice and the sham control group of SAMP8 mice (SAMP8 without plant enzymes administration) showed a significant reduction in arrival time, and in the probe test, it was divided into 4 divisions. Moreover, there was a significant increase in dwell time and number of crossings of the virtual platform area. The plant enzyme-treated group tended to have a shorter arrival time than the sham group, but not significantly different. Serum peroxy radicals were significantly suppressed in the plant enzyme-treated group compared with the sham group. Plant enzyme inhibited the peroxy radical in comparison to a sham control. With plant enzymes treatment, the lipid peroxidation level was significantly lowered in the brain tissue compared with the sham control group (p < 0.05. Serotonin (5-HT) levels were significantly higher in the brain tissue of plant enzymes -treated mice than in that of sham control mice. There was no significant difference in the brain lipid peroxide concentration between the plant enzyme administration group and the sham group. In contrast, the serotonin concentration in the brain was significantly different between the plant enzymes administration group and the sham control group. The high neuron density (CA1 region) in the hippocampus of animals in the plant enzymes administration group indicates a possible improvement in memory.

Polylactic Acid-Based Microplastic Particles Induced Oxidative Damage in Brain and Gills of Goldfish Carassius auratus

The effect of 96 h exposure of the goldfish Carassius auratus to two different types of bioplastic particles, originating from commercial shopping bag (Bag, ~5 mm) and polylactic acid-based (PLA) cup (Cup, ≤5 mm), and petroleum-based polyamide particles (PA, 0–180 µm) was studied. All particles were studied as virgin and after simulated UV-degradation (at concentration 30 mg L−1). The experiments were conducted according to OECD 203 test guidelines. The toxicity endpoint evaluated in fish brain and gills was lipid peroxidation (LPO) quantified as nmol thiobarbituric acid reactive substances (TBARs) mg−1 protein. The results indicated that indicatively compostable PLA bioplastic Cup induced significant LPO in the brain and/or gills of the goldfish, in contrast to the particles from Bag and PA (in the brain, Cup > Bag > PA; in the gills, Cup > Bag). The UV-degradation of the particles of all studied types had no significant effect on the LPO level compared to virgin particles. While the increase of LPO in fish gills and brain upon exposure to PLA-plastic particles can be transitory in the long-term perspective, our results point to the necessity of a thorough investigation of the hazard of bioplastics at different state of environmental degradation/weathering.

Germinated brown rice extract reduces brain lipid peroxidation and Aβ levels via regulations of BACE1, RAGE, IDE and LRP1 expressions in high fat/cholesterol diet-fed rats

A strong association presents between excessive amyloid-β (Aβ) buildup and oxidative stress with Alzheimer’s disease (AD). In view of the multifaceted neuroprotective effects of some dietary elements, the beneficial effect of germinated brown rice was investigated using a high fat/cholesterol diet (HFCD)-induced sporadic rat model of AD. Seven groups, including normal control, HFCD, and HFCD treated with Donepezil, Simvastatin, Probucol, and germinated brown rice ethyl acetate extract (GBR-EA; 100 and 200 mg/kg bw) were included in the present study. Biochemical assays, brain lipid peroxidation, mRNA and protein levels involved in Aβ processing and metabolism pathways were analyzed. HFCD-fed rats exhibited increased brain lipid peroxidation and Aβ levels, as well as altered expressions of proteins involved in Aβ generation, degradation and clearance. GBR-EA treatment groups showed significant reduction in lipid peroxidation and Aβ levels when compared to HFCD group. The effects of GBR-EA on Aβ levels are likely through the modulation of BACE1 and Presenilins, as well as induction of Aβ clearance and degradation. The findings revealed the potential use of germinated brown rice to attenuate HFCD diet-induced neurodegenerative alterations, likely due to reduced brain inflammation, as well as modulation of Aβ processing and metabolism pathways.

Carbon Nanodots Attenuate Lipid Peroxidation in the LDL Receptor Knockout Mouse Brain.

Abnormal cholesterol metabolism can lead to oxidative stress in the brain. Low-density lipoprotein receptor (LDLr) knockout mice are models for studying altered cholesterol metabolism and oxidative stress onset in the brain. Carbon nanodots are a new class of carbon nanomaterials that possess antioxidant properties. The goal of our study was to evaluate the effectiveness of carbon nanodots in preventing brain lipid peroxidation. LDLr knockout mice and wild-type C57BL/6J mice were treated with saline or 2.5 mg/kg bw of carbon nanodots for a 16-week period. Brains were removed and dissected into the cortex, midbrain, and striatum. We measured lipid peroxidation in the mouse brain tissues using the Thiobarbituric Acid Reactive Substances Assay and iron and copper concentrations using Graphite Furnace Atomic Absorption Spectroscopy. We focused on iron and copper due to their association with oxidative stress. Iron concentrations were significantly elevated in the midbrain and striatum of the LDLr knockout mice compared to the C57BL/6J mice, whereas lipid peroxidation was greatest in the midbrain and cortex of the LDLr knockout mice. Treatment with carbon nanodots in the LDLr knockout mice attenuated both the rise in iron and lipid peroxidation, but they had no negative effect in the C57BL/6J mice, indicating the anti-oxidative stress properties of carbon nanodots. We also assessed locomotor and anxiety-like behaviors as functional indicators of lipid peroxidation and found that treatment with carbon nanodots prevented the anxiety-like behaviors displayed by the LDLr knockout mice. Overall, our results show that carbon nanodots are safe and may be an effective nanomaterial for combating the harmful effects caused by lipid peroxidation.

Oxidative Stress and Neurodegeneration in Animal Models of Seizures and Epilepsy.

Free radicals are generated in the brain, as well as in other organs, and their production is proportional to the brain activity. Due to its low antioxidant capacity, the brain is particularly sensitive to free radical damage, which may affect lipids, nucleic acids, and proteins. The available evidence clearly points to a role for oxidative stress in neuronal death and pathophysiology of epileptogenesis and epilepsy. The present review is devoted to the generation of free radicals in some animal models of seizures and epilepsy and the consequences of oxidative stress, such as DNA or mitochondrial damage leading to neurodegeneration. Additionally, antioxidant properties of antiepileptic (antiseizure) drugs and a possible use of antioxidant drugs or compounds in patients with epilepsy are reviewed. In numerous seizure models, the brain concentration of free radicals was significantly elevated. Some antiepileptic drugs may inhibit these effects; for example, valproate reduced the increase in brain malondialdehyde (a marker of lipid peroxidation) concentration induced by electroconvulsions. In the pentylenetetrazol model, valproate prevented the reduced glutathione concentration and an increase in brain lipid peroxidation products. The scarce clinical data indicate that some antioxidants (melatonin, selenium, vitamin E) may be recommended as adjuvants for patients with drug-resistant epilepsy.

Oxidative Stress in a Wild Population of the Freshwater Fish Hyphessobrycon Luetkenii Chronically Exposed to a Copper Mining Area: New Insights into Copper Toxicology.

In this study, we examine markers of oxidative stress in the tetra Hyphessobrycon luetkenii collected from two locations in the copper contaminated João Dias creek (southern Brazil). Also, specimens were translocated from a clean reference section of the creek to a polluted stretch and vice-versa. Fish were held at in submerged cages for 96h and then sacrificed. Nuclear abnormalities in erythrocytes and total antioxidant capacity, lipid peroxidation and protein carbonylation in gills, brain, liver and muscle displayed similar trends in both groups. Lipid peroxidation increased in all tissues of individuals translocated to the polluted site but only in liver and muscle of those translocated to the reference site. Increased protein carbonylation was also observed in gills of individuals translocated to the reference location. These results suggest similar oxidative stress among fish from the reference and polluted locations and that long-term metals exposure may require adaptations toward oxidative stress responses.

Sea urchin (Diadema savignyi) extract as a novel protective agent against cisplatin induced neurotoxicity in rats

Neurotoxicity is a severe side effect of platinum compounds used for cancer chemotherapy such as Cisplatin. This neurotoxicity leads to severe cognitive and nervous dysfunction, therefore, limiting the dose of Cisplatin and compromising the treatment protocol.The present study investigates the neuroprotective effect of Sea Urchins which is a marine animal known for its rich bioactive compounds. Male Sprague Dawley rats received Cisplatin (2 mg/kg body weight) for 4 weeks, two times per week, followed by Sea Urchin extracts (50 and 100 mg/kg body weight) twice weekly for 4 weeks.Results show that rats treated with Urchin’s extracts showed a significant improvement in the thermal (heat and cold) sensitivity compared to untreated rats. Liver enzymes Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) and Urea levels were also significantly decreased back to normal following treatment with sea urchin extracts. Brain tissue oxidative stress marker Nitric oxide (NO) and lipid peroxidation marker Malondialdehyde (MDA) increased significantly in the cisplatin-treated rats while the reduced glutathione levels (GSH) and catalase activity (CAT) showed a significant decrease. Treatment with sea Urchin extracts reversed these changes.Histological and immunohistochemical examination of the cerebral cortex reveled degenerative changes such as karyopyknosis and shrunken necrotic ghost like neurons in the cisplatin treated groups. There was also strong positive Glial fibrillary acidic protein (GFAP) reactivity and a negative B-cell leukemia/lymphoma 2 protein (Bcl2) reaction in most apparent neurons, indicating strong apoptotic changes. Treatment with Urchin extracts reversed these changes. Quantification of cerebral cortex neurons also revealed the strong effect of the extracts. Cisplatin treated groups showed 3708 cells/ mm3 compared to 8091 cells/mm3 in the normal rats. Extract treatment increased the neuronal numbers to almost normal levels. Quantification of the Immuno-histochemical expression of GFAP showed an increase by 10-folds after cisplatin administration. A remarkable decline from the cisplatin group was seen in the extract treated groups.In Conclusion, Sea Urchins extracts possess a strong neuroprotective activity and could provide a novel therapeutic method to prevent Cisplatin-induced neurotoxicity.

Evaluating the effect of ginsenoside Rg1 on CPF-induced brain injury in mice via PI3k/AKT pathway.

Organophosphorus pesticides (OPs) have long been used extensively on agricultural land and can lead to significant improvements in crop yields. Due to occupational exposure, humans are exposed to pesticides through dermal contact, inhalation, and ingestion. The effects of OPs on the organism are currently studied for their effects on livers, kidneys, hearts, blood indicators, neurotoxicity,and teratogenic, carcinogenic, and mutagenic effects, while studies in the direction of brain tissue damage have not been reported in detail. Previous reports have confirmed that ginsenoside Rg1 is a prominent and representative tetracyclic triterpenoid derivative rich in ginseng and has good neuroprotective activity. Considering that, the aim of this study was to establish a mouse model of brain tissue injury by using the OP-type pesticide chlorpyrifos (CPF) and to explore the therapeutic effects and possible molecular mechanisms of Rg1. Mice in the experimental group were pre-protected with Rg1 by gavage for 1 week, and brain tissue damage was induced using CPF (5 mg/kg for 1 week) to assess the effect of Rg1 (80 and160 mg/kg for 3 weeks) in alleviating brain damage. Morris water maze and histopathological analysis were performed to assess cognitive function and pathological changes in the mouse brain, respectively. Protein expression levels of Bax, Bcl-2, Caspase-3, Cl-Cas-3, Caspase-9, Cl-Cas-9, phosphoinositide 3-kinase (PI3K), phosphorylated-PI3K, protein kinase B (AKT), and phosphorylated-AKT were quantified by protein blotting analysis. Rg1 obviously restored CPF-induced oxidative stress damage in mouse brain tissue, increased the levels of antioxidant parameters (total superoxide dismutase, total antioxidative capacity, and glutathione) in the brain, and significantly reduced the overexpression of apoptosis-related proteins induced by CPF. At the same time, Rg1 also markedly attenuated the histopathological changes in the brain induced by CPF exposure. Mechanistically, Rg1 could effectively activate the phosphorylation of PI3K/AKT. Furthermore, molecular docking studies revealed a stronger binding capacity between Rg1 and PI3K. Rg1 attenuated neurobehavioural alterations and reduced lipid peroxidation in the mouse brain to a great extent. Apart from that, Rg1 administration improved brain histopathology in CPF-induced rats. All results suggest that ginsenoside Rg1 has potential antioxidant effects on CPF-induced oxidative brain injury, and it is evident that Rg1 could be used as a promising therapeutic strategy for the study of brain injury from OPpoisoning.

Cadmium and Chlorpyrifos Induced Lipid Peroxidation in Brain, Liver and Kidney of Wistar Rats

The work was designed with 4 groups for 28 days. 1: Control. 2: CdCl2 @ 22.5mg/ kg b.wt / oral. 3: CPF @ 25 mg/ kg b.wt /per oral. 4: CdCl2@22.5 mg + CPF @ 25 mg/ kg b.wt /per oral. Higher mean values of liver, kidney and brain TBARS were observed in G-2, 3 and 4 on 15th and 29th day. Liver section in group 2 revealed mild degenerative changes in group 3; in group 4 mild to moderate peri portal fibrosis. Kidney section in group 2 showed shrunken glomeruli, necrosis; kidney section showed degeneration and necrosis of tubular epithelium with casts in the lumen in group 3 and necrosis with casts in the lumen in group 4. Brain section in group 2 showed mild perivascular cuffing, mild to moderate degeneration of Purkinji cells in group 3 and in group 4 degeneration of Purkinje cells. Effects in G-4 were severe than individual groups due to synergistic action of the combined pollutants than the individual effects.

The inhibitory effect of Cannabis Sativa L. and Morus nigra L. against lipid peroxidation in goat liver and brain homogenates.

The present study was aimed to evaluate the antioxidant potential and inhibitory effect ofCannabis sativa and Morus nigra against lipid peroxidation in goat brain and liver homogenates. The formation of free radicals, highly reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a normal metabolic process for cellular signaling and countering the antigens. However, they may cause serious damage if they produced at amplified tolls. In addition, metabolic disorders also serve as sources of these reactive species. Although the issue can be addressed through supplements and other phytochemicals. In this study, two plant species were evaluated for their biological potential by employing a spectrum of antioxidant assays. The antioxidant activity was performed by lipid peroxidation assay. The water extract prepared from leaves of Cannabis sativa and Morus nigra showed significant (P<0.05) inhibition as compared to control i.e., 522.6±0.06 and 659.97±0.03 µg/mL against iron-induced lipid peroxidation in goat brain homogenate while the inhibitions were 273.54±0.04 and 309.18±0.05 µg/mL against nitroprusside induced lipid peroxidation of the brain. The iron and nitroprusside induced lipid peroxidation was also significantly inhibited by leaf extracts of Cannabis sativa and Morus nigra in liver homogenates such as 230.63±0.52 and 326.91±0.01 µg/mL (iron-induced) while 300.47±0.07 and 300.47±0.07 µg/mL (nitroprusside induced), respectively. The extracts of Cannabis sativa extract showed promising activity (96.04±0.060%) against DPPH radicals while Morus nigra showed a moderate activity (34.11±0.120%). The results suggest that different accessions ofCannabis sativa and Morus nigra are a potential source of antioxidants and have a therapeutic effect against disease induced by oxidative stress and hence can be used for novel drug discovery and development.

Anethole prevents high-calorie diet-induced brain lipid peroxidation in rats and normalizes superoxide dismutase activity

Anethole prevents high-calorie diet-induced brain lipid peroxidation in rats and normalizes superoxide dismutase activity

Target Organ Toxicity in Rats After Subchronic Oral Exposure to Soil Extracts Containing a Complex Mixture of Contaminants.

Complex mixtures of unknown contaminants present a challenge to identify toxicological risks without using large numbers of animals and labor-intensive screens of all organs. This study examined soil extracts from a legacy-contaminated pesticide packaging and blending site. HepG2 cytotoxicity was used as an initial screen of 18 soil samples; then, three extracts (A, B and C) from different locations at the study site were used for testing in animals. The first two extracts were identified as the most toxic in vitro, and the latter extract obtained from a location further from these two toxic sampling sites. Then, target organ toxicities were identified following biweekly oral gavage for one month of three soil extracts (0.1% in polyethylene glycol or PEG) compared to vehicle control in male Sprague-Dawley rats (n = 9-10/group). Exposure to extract A significantly increased neutrophils and lymphocytes compared to control. In contrast, all extracts increased plasma α-2 macroglobulin and caused mild-to-moderate lymphocytic proliferation within the spleen white pulp, all indicative of inflammation. Rats exposed to all soil extracts exhibited acute tubular necrosis. Cholinesterase activity was significantly reduced in plasma, but not brain, after exposure to extract A compared to control. Increased hepatic ethoxyresorufin-o-deethylase activity compared to control was observed following exposure to extracts A and B. Exposure to soil extract C in rats showed a prolonged QTc interval in electrocardiography as well as increased brain lipid peroxidation. Candidate contaminants are organochlorine, organophosphate/carbamate pesticides or metabolites. Overall, HepG2 cytotoxicity did not successfully predict the neurotoxicity and cardiotoxicity observed with extract C but was more successful with suspected hydrocarbon toxicities in extracts A and B. Caution should be taken when extrapolating the observation of no effects from in vitro cell culture to in vivo toxicity, and better cell culture lines or assays should be explored.

Flavonoid-enrich extract of Autranella congolensis (Sapotaceae) protects against aluminium chloride-mediated Alzheimer's disease-like oxidative stress in rat through the antioxidant properties.

Oxidative stress (OS) is well established as a major event in Alzheimer's disease (AD) pathology. One of the mostly-researched classes of antioxidants to manage with overwhelming OS include flavonoids. This study was aimed to investigate the protective effect of A. congolensis extract (HEEAC) on AlCl3-mediated AD-like OS and assess the contribution of its antioxidant flavonoid contents.Female Wistar (250-300g) rats received orally 50mg/Kg bw of AlCl3, followed one hour later by doses (150 or 300mg/kg) of HEEAC or vitamin E at 100mg/kg daily for eight consecutive weeks. OS related biomarkers were evaluated at the end of treatment. To assess the contribution of flavonoid contents to its activity, HEEAC was fractioned using solvent of varying polarities. Flavonoid-rich extracts obtained were tested for their antioxidant capacity.AlCl3 administration significantly lowered antioxidant enzymes (catalase, glutathione peroxidase) and aconitase levels, reduced total thiol and thiol protein levels and increased lipid peroxidation and protein oxidation levels in brain. When co-administrated with HEEAC at 150mg/kg, all of these OS related biomarkers were significantly moderated. The efficacity of the extract was significantly higher than vitamin E. Flavonoid-rich fractions extracted mainly n-butanol fraction show strong antioxidant activity, which can be considered as the major antioxidant fraction of this plant.HEEAC protect brain cells against oxidative damage induced by AlCl3, specifically through the strong antioxidant property of its n-butanol flavonoid-rich fraction, which may be a promising agent for preventing oxidative damage in AD.

Polyphenol bioavailability and modulatory potential on brain antioxidative markers in C57BL/6 mouse

Background and purpose: Prunus spinose L. is a traditionally consumed, recently scientifically reexamined plant. Brain bioavailability and functionality of polyphenols (PPH) of blackthorn flower extract (PSE) was investigated.Materials and methods: C57BL/6 mice received oral daily repeated doses of 25 mg/kg body weight of total PSE polyphenols for 28 days. Brain concentrations of individual polyphenols from PSE were determined by UPLC/MS on 1st,7th, 14th, 21st, and 28th day. Brain antioxidative defense markers were examined as indicators of functionality after bioaccumulation.Results: A total of 68.7% PPH present in PSE were detected in the brain. Higher (p≤0.05) Cmax/AUClast in the PSE treatment vs. control group was recorded for 59.1% of brain detected compounds, indicating relatively good bioaccumulation in the brain. The highest present compounds in PSE were not necessarily the ones mostly bioapsorbed in the brain. Kaempherols were not significantly distributed, opposite to phenolic acids, quercetins or epicgaloatechin-3-gallate. The compounds with the highest concentrations on 28th day were 4-p-coumaroylquinonic acid, (-)-epicatechin, quercetin-3-O-rutinoside, quercetin–rhamnoside, kaempherol-3-rutinoside and quercetin-3-gucoside. Brain lipid peroxidation (MDA) decreased (p&lt;0.05) on the 21st and 28th day in the PSE group. Increase (p&lt;0.05) in GSH concentration was observed on the 21st and 28th and SOD activity on the 28th day. Catalase activity was unchanged. It could be hypothesized that highest PPH concentration-ratios, caused reduction of lipid peroxidation by radical scavenging and simultaneous induction of glutathione and SOD pathways.Conclusions: Screened compounds could be candidates for examining or creation of brain targeted “neuro-nutriceuticals” polyphenol mixtures.

Increased unsaturated lipids underlie lipid peroxidation in synucleinopathy brain

Lipid peroxidation is a process of oxidative degradation of cellular lipids that is increasingly recognized as an important factor in the pathogenesis of neurodegenerative diseases. We were therefore interested in the manifestation of lipid peroxidation in synucleinopathies, a group of neurodegenerative diseases characterized by the central pathology of α-synuclein aggregates, including Parkinson’s disease, multiple system atrophy, dementia with Lewy bodies and Alzheimer’s disease with Lewy bodies. We assessed lipid peroxidation products, lipid aldehydes, in the amygdala, a common disease-affected region in synucleinopathies, and in the visual cortex, a disease-unaffected region. We found that the levels of lipid aldehydes were significantly increased in the amygdala, but not in the visual cortex. We hypothesized that these increases are due to increases in the abundance of unsaturated lipids, since lipid aldehydes are formed from unsaturated lipids. We undertook a comprehensive analysis of membrane lipids using liquid chromatography-mass spectrometry and found that unsaturated phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and sphingomyelin were specifically elevated in the amygdala and correlated with increases in lipid aldehydes. Furthermore, unsaturated phosphatidylethanolamine levels were associated with soluble α-synuclein. Put together, these results suggest that manifestation of lipid peroxidation is prevalent in synucleinopathies and is likely to be due to increases in unsaturated membrane lipids. Our findings underscore the importance of lipid peroxidation in α-synuclein pathology and in membrane structure maintenance.

Dietary vitamin B6 restriction aggravates neurodegeneration in mice fed a high-fat diet

AimsIt is well known that a low-status of B vitamins is associated with cognitive impairment. However, the impact of vitamin B6 (VB6) restriction on neurodegenerative diseases and its underlying mechanisms are rarely understood. This study investigated whether VB6 restriction aggravates neurodegeneration in mice fed either a low-fat (LF) control diet or a high-fat (HF) diet. Main methodsSix-week-old male C57BL/6J mice were divided into 4 groups (LF7, LF1, HF7 and HF1) and fed either an LF diet [7 mg pyridoxine (PN)/kg diet], an LF with 1 mg PN/kg diet, an HF diet or an HF with 1 mg PN/kg diet for 16 weeks. Brain cortex and hippocampus were collected and used for the determination of biochemical parameters including VB6, lipid peroxides, and neurodegeneration-related mRNA and protein levels. Key findingsVB6 restriction reduced levels of the biologically active form of VB6, pyridoxal phosphate (PLP) in the brain. Low consumption of VB6 inactivated brain-derived neurotrophic factor signaling and cell proliferation, and induced oxidative stress, endoplasmic reticulum stress and apoptotic cell death. Significant correlation between brain lipid peroxide levels and PLP levels were observed. VB6 restriction also induced characteristic features of neurodegeneration such as amyloid-β deposition and tau hyperphosphorylation. Similarly, high-fat diet increased parameters associated with neurodegeneration. Aggravating effects of VB6 restriction were observed in both LF control and HF groups. SignificanceDietary VB6 restriction plays a key role in neurodegeneration, and VB6 restriction worsens HF-induced neuronal damage in mice. Our study emphasizes the essential role of VB6 in maintaining brain health.