Brain Malondialdehyde Levels Research Articles

A comparison of cognitive decline in aged mice and mice treated with aftin-4

Dementia, especially Alzheimer’s disease, presents a major clinical challenge, and researchers are still searching for an optimal animal model. To address this gap, we compared male and ovariectomized female C57BL/6 mice treated with 30 mg/kg aftin-4, which induces neurodegeneration, with naturally aged (15–16 months old) mice not treated with aftin-4. We performed a series of behavioral tests; measured postmortem plasma β-amyloid levels (Aβ1–40 and Aβ1–42) and the levels of the oxidative stress indicators glutathione peroxidase (GPx), superoxide dismutase (SOD) and malondialdehyde (MDA); and evaluated astrocytic reactivity in the brain using glial fibrillary acid protein (GFAP) levels. Our results revealed no behavioral changes in the aged or aftin-4-treated mice compared with the control mice. Aftin-4 mice presented lower brain MDA levels and no detectable changes in plasma Aβ levels. In general, female mice had higher GPx and SOD levels and lower Aβ1–42 levels than male mice did. In contrast, aged and aftin-4-treated male mice presented elevated levels of GFAP, indicating astrocyte damage. Our results could not confirm that either aftin-4-treated or aged mice are reliable models for dementia. However, the observed molecular changes suggest that male animals may be more susceptible to oxidative stress and brain damage than females are. This study demonstrates the complexity of modeling dementia in animals and the importance of future studies in this area.

Myrtenol-Loaded Fatty Acid Nanocarriers Protect Rat Brains Against Ischemia-Reperfusion Injury: Antioxidant and Anti-Inflammatory Effects.

This research investigated the preventive effects of myrtenol (MYR), fatty acid nanocarriers (FANC), and myrtenol-loaded FANC (MYR + FANC) on neurological disturbance, stroke volume, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and tumor necrosis factor-alpha (TNF-α) in the brain with ischemia-reperfusion injuries induced by middle cerebral artery occlusion (MCAO) in rats. Seventy two Wistar male rats were divided into six main groups. The groups were sham, ischemia-reperfusion group (MACO), MACO-MYR (50 mg/kg), MACO-FANC (50 and 100 mg/kg), and MACO-MYR + FANC (50 mg/kg). Stroke volume, neurological deficit scores, and the brain levels of MDA, SOD, and TNF-α were examined with TTC staining, observation, and ELISA, respectively. Pretreatment with MYR, FANC (100 mg/kg), and MYR + FANC reduced the neurological deficit score and cerebral infarction volume. MYR, FANC (100 mg/kg), and MYR + FANC pretreatment increased and decreased brain SOD and MDA levels compared to MACO group, respectively. The TNF-α level decreased in the MYR + FANC group compared to MCAO and MCAO-MYR groups in the brain. The use of FANC (100 mg/kg), MYR, and MYR + FANC has protective effects against oxidative stress and ischemia-reperfusion injury. FANC probably improve the bioavailability of MYR, as MYR+ FANC had more therapeutic effects on the reduction of ischemia-reperfusion injuries, inflammation, and oxidative stress.

Fabrication of diosmin loaded food-grade bilayer nanoparticles with modified chitosan and soy peptides and antioxidant properties examination

Diosmin is a flavonoid derived from plants, possessing anti-inflammatory, antioxidant, antidiabetic, neuroprotective and cardiovascular protective properties. However, diosmin has low solubility in water, leading to low bioavailability. In this study, we constructed bilayer nanoparticles with trimethyl chitosan and soy peptides to improve the oral bioaccessibility and bioavailability of diosmin, and determined the characteristics and antioxidant properties of the diosmin-loaded nanoparticles. The results showed that the size of the nanoparticles was around 250 nm with the encapsulation efficiency higher than 97 %, and the nanoparticles were stable under regular conditions. In vitro digestion suggested the nanoparticles could protect diosmin from releasing in gastric digestion but promote the bioaccessibility of diosmin in intestine. Furthermore, the diosmin-loaded nanoparticles presented excellent antioxidant activities in vitro and significantly decreased the Lipopolysaccharides-induced brain Malondialdehyde (MDA) level by oral administration. Therefore, the reported nanoparticles may be an effective platform for improving the oral bioavailability of diosmin.

Metabolomic modelling and neuroprotective effects of carvacrol against acrylamide toxicity in rat's brain and sciatic nerve.

The study aimed to investigate the harmful effects of acrylamide (AA), which forms in carbohydrate-rich foods at temperatures above 120°C, on the central and peripheral nervous systems and to evaluate the potential neuroprotective effects of carvacrol (CRV). Male Wistar Albino rats were subjected to AA (40 mg/kg/bw/day) and CRV (50 mg/kg/bw/day) for 15 days. Following the last administration, evaluations revealed disrupted gait, heightened thermal sensitivity and altered paw withdrawal thresholds in AA-exposed rats. Notably, AA reduced glutathione (GSH) and raised malondialdehyde (MDA) levels in both brain and sciatic nerve tissues. AA raised nuclear factor erythroid 2-related factor 2 (Nrf2), caspase 3 and nuclear factor κB (NF-κB) gene expressions while decreasing NR4A2. CRV co-administration mitigated gait abnormalities, elevated GSH levels and lowered MDA levels in both tissues. CRV also modulated gene expression, reducing Nrf2 and NF-κB while increasing NR4A2. Histopathological signs of AA-induced neurodegeneration and elevated glial fibrillary acidic protein levels observed in brain and sciatic nerve tissues were rectified with simultaneous administration of CRV, thereby demonstrating neuroprotective efficacy in both regions. This study is pioneering in demonstrating CRV's neuroprotective potential against AA-induced neurotoxicity in both central and peripheral nervous systems, effectively addressing limitations in the literature. In conclusion, the study revealed AA-induced neurodegeneration in the brain and sciatic nerve, with CRV significantly mitigating this neurotoxicity. This novel research underscores CRV's promise as a neuroprotective agent against AA-induced adverse effects in both the central and peripheral nervous systems.

A single dose of lipopolysaccharide injection exacerbates synaptic engulfment by microglia, and dendritic spine loss in high‐fat diet‐induced obese rats

AbstractBackgroundDiet‐induced obesity can lead to develop endotoxemia and cognitive decline (1). A previous study in Alzheimer’s disease model demonstrated that an increase in the colocalization of C1q, a classical complement protein, and microglia occurred, when those microglia increased synaptic engulfment, resulting in increased synaptic‐pruning process and synaptic loss (2). However, the effects of lipopolysaccharide (LPS) as endotoxin on peripheral inflammation, blood‐brain barrier(BBB) integrity, brain oxidative stress, synaptic engulfment by microglia, synaptic plasticity, and cognitive function in high‐fat diet‐induced obese rats have never been investigated.MethodSixteen male Wistar rats were randomly assigned to receive either a normal diet (ND, n = 8) or the high‐fat diet (HFD, n = 8) for 12 weeks. All animals in each dietary group were subsequently assigned into 2 subgroups (n = 4 /subgroup) to receive either a single dose of vehicle (1 ml of 0.9% normal saline solution, intraperitoneal (i.p.) injection, or LPS (0.5 mg/kg, i.p.). After the injections for 12‐16 hours, all animals were measured for cognitive function and the blood was collected. Then, animals were sacrificed, and their brains and spleens were obtained for further investigation.ResultAll HFD‐fed rats exhibited peripheral inflammation as indicated by increased spleen IL‐1β protein levels, BBB disruption as indicated by the reduction of hippocampal claudia‐5 protein levels, and increased brain oxidative stress as indicated by the increased brain malondialdehyde levels (p<0.05, Figure 1). Interestingly, LPS‐treated ND‐fed rats and vehicle‐treated HFD‐fed rats equally impaired microglial function by increasing synaptic engulfment as indicated by the increase in C1q colocalized in microglia and the decreased dendritic spine density (p<0.05, Figure 1). The results demonstrated that these parameters were aggravated in LPS‐treated HFD‐fed rats. Lastly, all HFD‐fed rats decreased the preference index of novel object location and recognition test suggesting long‐term HFD consumption caused cognitive decline (p<0.05, Figure 1).ConclusionLong‐term HFD consumption, but not LPS alone, caused cognitive decline by increasing peripheral inflammation, disrupting BBB integrity, increasing brain oxidative stress, increasing synaptic engulfment by microglia, and decreasing synaptic plasticity. Microglia are susceptible to impair their function in response to LPS, which potentially worsen brain pathologies in obese condition.

Effect of neonatal melatonin administration on behavioral and brain electrophysiological and redox imbalance in rats.

Melatonin (MLT) reportedly has beneficial effects in neurological disorders involving brain excitability (e.g., Epilepsy and Migraine) and behavioral patterns (e.g., Anxiety and Depression). This study was performed to investigate, in the developing rat brain, the effect of early-in-life administration of two different doses of exogenous MLT on behavioral (anxiety and memory) and electrophysiological (CSD analysis) aspects of brain function. Additionally, brain levels of malondialdehyde (MDA) and superoxide dismutase (SOD), both cellular indicators of redox balance status, were evaluated. We hypothesize that MLT differentially affects the behavioral and CSD parameters as a function of the MLT dose. Male Wistar rats received, from the 7th to the 27th postnatal day (PND), on alternate days, vehicle solution, or 10 mg/kg/or 40 mg/kg MLT (MLT-10 and MLT-40 groups), or no treatment (intact group). To perform behavioral and cognition analysis, from PND30 to PND32, they were tested in the open field apparatus, first for anxiety (PND30) and then for object recognition memory tasks: spatial position recognition (PND31) and shape recognition (PND32). On PND34, they were tested in the elevated plus maze. From PND36 to 42, the excitability-related phenomenon known as cortical spreading depression (CSD) was recorded, and its features were analyzed. Treatment with MLT did not change the animals' body weight or blood glucose levels. The MLT-10 treatment, but not the MLT-40 treatment, was associated with behaviors that suggest less anxiety and improved memory. MLT-10 and MLT-40 treatments, respectively, decelerated and accelerated CSD propagation (speed of 2.86 ± 0.14 mm/min and 3.96 ± 0.16 mm/min), compared with the control groups (3.3 ± 0.10 mm/min and 3.25 ± 0.11 mm/min, for the intact and vehicle groups, respectively; p < 0.01). Cerebral cortex levels of malondialdehyde and superoxide dismutase were, respectively, lower and higher in the MLT-10 group but not in the MLT40 group. Our findings suggest that MLT intraperitoneal administration during brain development may differentially act as an antioxidant agent when administered at a low dose but not at a high dose, according to behavioral, electrophysiological, and biochemical parameters.

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

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

Resveratrol plays neuroprotective role on ketamine-induced schizophrenia-like behaviors and oxidative damage in mice

This study aimed to determine effects of the resveratrol on ketamine-induced schizophrenia-like behaviors and oxidative damage in mice. Twenty-four male mice were allocated into four experimental groups as control, ketamine (20 mg/kg), resveratrol (80 mg/kg) and co-administration of the ketamine (20 mg/kg) + resveratrol (80 mg/kg). Mice were received resveratrol for 30 days and ketamine was used for an animal model of schizophrenia and was injected from days 16 to 30 of the study. After the drug administration was finished, schizophrenia-like behaviors were evaluated using object recognition test, tail suspension test, forced swimming test and open field test and brain malondialdehyde, glutathione peroxidase, superoxide dismutase and catalase levels were determined. According to the results, ketamine treatment significantly decreased body weight and pretreatment with resveratrol elevated body weight compared to ketamine group (P < 0.05). Ketamine treatment significantly decreased number of the cross in open field test and pretreatment with resveratrol improved i (P < 0.05). Immobility time in tail suspension and forced swimming tests increased in mice treated with ketamine (P < 0.05). Pretreatment with resveratrol diminished immobility time compared to ketamine group (P < 0.05). Ketamine significantly decreased memory deficits while pretreatment with resveratrol significantly reduced the memory deficits induced by ketamine (P < 0.05). Brain MDA increased in both cortical and sub-cortical area in ketamine treated mice while pretreatment with resveratrol decreased ketamine-induced elevation in MDA (P < 0.05). Ketamine significantly decreased brain SOD, GPx and CAT levels while pretreatment with resveratrol improved SOD, GPx and CAT levels (P < 0.05). Findings suggested resveratrol has neuroprotective effects against ketamine-induced behavioral deficits and oxidative damages.

Evaluation of Nootropic Potential of Aerva persica Roots against D-galactose-induced Memory Impairment.

The primary phytoconstituents reported to have neuroprotective effects are flavonoids and phenolic compounds. Aerva persica roots are reported to be rich in flavonoids and phenolic compounds. Therefore, this study aimed to explore the nootropic potential of Aerva persica roots. The objective of this study was to evaluate the nootropic potential of Aerva persica roots against D-galactose-induced memory impairment. In this study, the roots of Aerva persica were extracted with 70% ethanol. The obtained extract was evaluated for total phenolic content using the Folin-Ciocalteu method and total flavonoid content using the aluminium chloride colorimetric assay. Afterward, the acute oral toxicity of the extract was determined following the Organisation for Economic Co-operation and Development (OECD) guideline 423. Additionally, two doses of Aerva persica (100 and 200 mg/kg body weight (BW)) were evaluated for their nootropic potential against D-galactose-induced memory impairment. The nootropic potential of the crude extract was assessed through a behavioural study and brain neurochemical analysis. Behavioural studies involved the evaluation of spatial reference- working memory using the radial arm maze test and the Y-maze test. Neurochemical analysis was performed to determine the brain's acetylcholine, acetylcholinesterase, glutathione (GSH), and malondialdehyde (MDA) levels. The total phenolic content and total flavonoid content were found to be 179.14 ± 2.08 μg GAE/mg and 273.72 ± 3.94 μg QE/mg, respectively. The Aerva persica extract was found to be safe up to 2000 mg/kg BW. Following the safety assessment, the experimental mice received various treatments for 14 days. The behavioural analysis using the radial maze test showed that the extract at both doses significantly improved spatial reference-working memory and reduced the number of total errors compared to disease control groups. Similarly, in the Y-maze test, both doses significantly increased the alteration percentage and the percentage of novel arm entry (both indicative of intact spatial memory) compared to disease control. In neurochemical analysis, Aerva persica at 200 mg/kg significantly normalised the acetylcholine level (p<0.0001) and GSH level (p<0.01) compared to disease control. However, the same effect was not observed with Aerva persica at 100 mg/kg. Additionally, Aerva persica at 200mg/kg BW significantly decreased the acetylcholinesterase level (p<0.0001) and decreased the brain's MDA level (p<0.01) compared to the disease control, whereas the effect of Aerva persica at 100 mg/kg BW in reducing acetylcholinesterase was non-significant. Based on the results, it can be concluded that the nootropic potential of Aerva persica was comparable to that of the standard drug, Donepezil, and the effect might be attributed to the higher content of flavonoids and phenolic compounds.

Cola acuminata Mitigates Cognitive Deficit and Oxidative Stress in Mercury Chloride-induced Neurotoxicity in Male Wistar Rats

Cola acuminata is used in traditional medicine for the management of memory impairment and other neurodegenera-tive conditions. This study investigated the effects of Cola acuminata aqueous leaves extract (ALECA) on mercury chloride-induced neurotoxicity in Wistar rats. Twenty male Wistar rats weighing between 160 and 210 g were randomly assigned to four groups (n = 5). The control group received 0.5 mL of distilled water; the mercury chloride (HgCl2) group received HgCl2 (5 mg/kg b.w.); the ALECA100 and ALECA300 groups received ALECA (100 and 300 mg/kg b.w., respectively), followed by the administration of HgCl2 (5 mg/kg b.w.) for two weeks. The rats were subjected to behavioural tests in the Morris water maze and light and dark field box. The rats were then sacrificed to obtain their brains, which were homogenized for biochemical assays of acetylcholinesterase (AChE), malondialdehyde (MDA), total protein (TP), and glutathione (GSH) using standard methods. The results revealed a significant increase in escape latency, a significant decrease in probing frequency and brain GSH, and a significant (p&lt;0.05) increase in brain MDA and TP levels and AChE activity in the rats exposed to HgCl2. However, administration of either 100 or 300 mg/kg ALECA protected against memory impairment with a significantly reduced escape latency, increased probing frequency and brain GSH, and decreased (p&lt;0.05) MDA, TP and AChE. This study concludes that ALECA mitigated HgCl2-induced neurotoxicity via reduction of oxidative stress and enhanced cholinergic functions

Quetiapine Moderates Doxorubicin-Induced Cognitive Deficits: Influence of Oxidative Stress, Neuroinflammation, and Cellular Apoptosis.

Chemotherapy is considered a major choice in cancer treatment. Unfortunately, several cognitive deficiencies and psychiatric complications have been reported in patients with cancer during treatment and for the rest of their lives. Doxorubicin (DOX) plays an important role in chemotherapy regimens but affects both the central and peripheral nervous systems. Antipsychotic drugs alleviate the behavioral symptoms of aging-related dementia, and the atypical class, quetiapine (QUET), has been shown to have beneficial effects on various cognitive impairments. The present investigation aimed to determine the possible mechanism underlying the effect of thirty-day administrations of QUET (10 or 20 mg/kg, p.o.) on DOX-induced cognitive deficits (DICDs). DICDs were achieved through four doses of DOX (2 mg/kg, i.p.) at an interval of seven days during drug treatment. Elevated plus maze (EPM), novel object recognition (NOR), and Y-maze tasks were performed to confirm the DICDs and find the impact of QUET on them. The ELISA tests were executed with oxidative [malondialdehyde (MDA), catalase, and reduced glutathione (GSH)], inflammatory [cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB), and tumor necrosis factor-alpha (TNF-α)], and apoptosis [B-cell lymphoma 2 (Bcl2), Bcl2 associated X protein (Bax), and Caspase-3] markers were assessed in the brain homogenate to explore the related mechanisms. DICD lengthened the transfer latency time in EPM, shortened the exploration time of the novel object, reduced the discrimination ability of the objects in NOR, and lowered the number of arm entries and time spent in the novel arm. QUET alleviated DICD-related symptoms. In addition, QUET reduced neuronal oxidative stress by reducing MDA and elevating GSH levels in the rat brain. Moreover, it reduced neuronal inflammation by controlling the levels of COX-2, NF-κB, and TNF-α. By improving the Bcl-2 level and reducing both Bax and Caspase-3 levels, it protected against neuronal apoptosis. Collectively, our results supported that QUET may protect against DICD, which could be explained by the inhibition of neuronal inflammation and the attenuation of cellular apoptosis protecting against oxidative stress.

Neuroprotective potency of mangiferin against 3-nitropropionic acid induced Huntington's disease-like symptoms in rats: possible antioxidant and anti-inflammatory mechanisms.

Huntington's disease (HD), a neurodegenerative disease, normally starts in the prime of adult life, followed by a gradual occurrence of psychiatric disturbances, cognitive and motor dysfunction. The daily performances and life quality of HD patients have been severely interfered by these clinical signs and symptoms until the last stage of neuronal cell death. To the best of our knowledge, no treatment is available to completely mitigate the progression of HD. Mangiferin, a naturally occurring potent glucoxilxanthone, is mainly isolated from the Mangifera indica plant. Considerable studies have confirmed the medicinal benefits of mangiferin against memory and cognitive impairment in neurodegenerative experimental models such as Alzheimer's and Parkinson's diseases. Therefore, this study aims to evaluate the neuroprotective effect of mangiferin against 3-nitropropionic acid (3-NP) induced HD in rat models. Adult Wistar rats (n = 32) were randomly allocated equally into four groups of eight rats each: normal control (Group I), disease control (Group II) and two treatment groups (Group III and Group IV). Treatment with mangiferin (10 and 20mg/kg, p. o.) was given for 14days, whereas 3-NP (15mg/kg, i. p.) was given for 7days to induce HD-like symptoms in rats. Rats were assessed for cognitive functions and motor coordination using open field test (OFT), novel object recognition (NOR) test, neurological assessment, rotarod and grip strength tests. Biochemical parameters such as oxidative stress markers and pro-inflammatory markers in brain hippocampus, striatum and cortex regions were evaluated. Histopathological study on brain tissue was also conducted using hematoxylin and eosin (H&E) staining. 3-NP triggered anxiety, decreased recognition memory, reduced locomotor activity, lower neurological scoring, declined rotarod performance and grip strength were alleviated by mangiferin treatment. Further, a significant depletion in brain malondialdehyde (MDA) level, an increase in reduced glutathione (GSH) level, succinate dehydrogenase (SDH), superoxide dismutase (SOD) and catalase (CAT) activities, and a decrease in tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) levels were observed in mangiferin treated groups. Mangiferin also mitigated 3-NP induced histopathological alteration in the brain hippocampus, striatum and cortex sections. It could be inferred that mangiferin protects the brain against oxidative damage and neuroinflammation, notably via antioxidant and anti-inflammatory activities. Mangiferin, which has a good safety profile, may be an alternate treatment option for treating HD and other neurodegenerative disorders. The results of the current research of mangiferin will open up new avenues for the development of safe and effective therapeutic agents in diminishing HD.

Lonicera japonica polysaccharides alleviate D-galactose-induced oxidative stress and restore gut microbiota in ICR mice

Lonicera japonica polysaccharides (LJPs) exhibit anti-aging effect in nematodes. Here, we further studied the function of LJPs on aging-related disorders in D-galactose (D-gal)-induced ICR mice. Four groups of mice including the control group, the D-gal-treated group, the intervening groups with low and high dose of LJPs (50 and 100 mg/kg/day) were raised for 8 weeks. The results showed that intragastric administration with LJPs improved the organ indexes of D-gal-treated mice. Moreover, LJPs improved the activity of superoxide dismutase (SOD), catalase (CAT) as well as glutathione peroxidase (GSH-Px) and decreased the malondialdehyde (MDA) level in serum, liver and brain. Meanwhile, LJPs restored the content of acetylcholinesterase (AChE) in the brain. Further, LJPs reversed the liver tissue damages in aging mice. Mechanistically, LJPs alleviate oxidative stress at least partially through regulating Nrf2 signaling. Additionally, LJPs restored the gut microbiota composition of D-gal-treated mice by adjusting the Firmicutes/Bacteroidetes ratio at the phylum level and upregulating the relative abundances of Lactobacillaceae and Bifidobacteriacesa. Notably, the KEGG pathways involved in hazardous substances degradation and flavone and flavonol biosynthesis were significantly enhanced by LJPs treatment. Overall, our study uncovers the role of LJPs in modulating oxidative stress and gut microbiota in the D-gal-induced aging mice.

Effects of methanol leaf extract of Dryopteris filix-mas on catalase activity and malondialdehyde levels in the brain of adult male Wistar rats

This study was carried out to determine the effect of methanol leaf extract of Dryopteris filix-mas on catalase (an antioxidant) activity and malondialdehyde (an oxidative stress marker) levels in brain of wistar rats. Methanol extract of Dryopteris filix-mas was prepared by Soxhlet extraction. Twenty (20) adults male wistar rats were used for this study. The animals were grouped into four groups; 1 (normal control); 2 (administered 100mg/kg of Dryopteris filix methanol leaf extract) and 3 (administered 250mg/kg of Dryopteris filix methanol leaf extract); 4 (Administered 500mg/kg of Dryopteris filix methanol leaf extract). The rats were so treated and after 21 days, were sacrificed. The brain of the rats was harvested and used to prepare brain tissue homogenates for the biochemical assay of catalase and MDA using standard procedures. Results obtained show that the varying doses of the plant extract caused a dose dependent increase in catalase activity when compared to the control group. However, the increases were found to be statistically insignificant (p&gt;0.05). Administration of 100mg/kg of the plant extract slightly decreased MDA level, while 250mg/kg and 500mg/kg slightly increased MDA levels in brain of the experimental animals after the 21days treatment period when compared to the control group. However, these observed changes in MDA levels were found to be statistically insignificant (p&gt;0.05). The results of this study shows that the different doses of the plant extract did not cause significant oxidative damage to the brain of the experimental animals.&#x0D;

Distinct signatures on d-galactose-induced aging and preventive/protective potency of two low-dose vitamin D supplementation regimens on working memory, muscular damage, cardiac and cerebral oxidative stress, and SIRT1 and calstabin2 downregulation.

Chronic administration of d-galactose (d-gal) in rodents reproduces the overproduction of reactive oxygen species of physiological aging. The present research shows for the first time distinct signatures on d-gal-induced aging (500 mg/kg, 6 weeks) and the preventive and protective potential of two vitamin D (50 IU) supplementation regimens (pre-induction and simultaneous, respectively) in two vital organs (heart and brain). d-gal-induced notorious alterations in working memory, a strong increase in brain malondialdehyde (MDA) oxidative levels, and strong downregulation of sirtuin 1 (SIRT1) in the heart and hippocampus and of calstabin2 in the heart. Cardiac and brain superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymatic antioxidant capacities were damaged, brain calstabin2 was downregulated, and neuropathology was observed. Heart damage also included a moderate increase in MDA levels, serologic lactate dehydrogenase (LDH), total creatine kinase (CK) activities, and histopathological alterations. The used dose of vitamin D was enough to prevent cognitive impairment, avoid muscular damage, hamper cardiac and cerebral oxidative stress, and SIRT1 and calstabin2 downregulation. Most importantly, the potencies of the two preventive schedules depended on the tissue and level of study. The pre-induction schedule prevented d-gal-induced aging by 1 order of magnitude higher than simultaneous administration in all the variables studied except for SIRT1, whose strong downregulation induced by d-gal was equally prevented by both schedules. The benefits of vitamin D for oxidative stress were stronger in the brain than in the heart. Brain MDA levels were more sensitive to damage, while SOD and GPx antioxidant enzymatic activities were in the heart. In this order, the magnitude of SOD, MDA, and GPx oxidative stress markers was sensitive to prevention. In summary, the results unveiled distinct aging induction, preventive signatures, and sensitivity of markers depending on different levels of study and tissues, which are relevant from a mechanistic view and in the design of targeted interventions.

Reparative, Neuroprotective and Anti-neurodegenerative Effects of Granulocyte Colony Stimulating Factor in Radiation-Induced Brain Injury Model.

This animal model aimed to compare the rat group that received brain irradiation and did not receive additional treatment (only saline) and the rat group that underwent brain irradiation and received Granulocyte colony stimulating factor (G-CSF) treatment. In addition, the effects of G-CSF on brain functions were examined by magnetic resonance (MR) imaging and histopathologically. This study used 24 female Wistar albino rats. Drug administration (saline or G-CSF) was started at the beginning of the study and continued for 15 days after whole-brain radiotherapy (WBRT). WBRT was given on day 7 of the start of the study. At the end of 15 days, the behavioral tests, including the three-chamber sociability test, open field test, and passive avoidance learning test, were done. After the behavioral test, the animals performed the MR spectroscopy procedure. At the end of the study, cervical dislocation was applied to all animals. G-CSF treatment positively affected the results of the three-chamber sociability test, open-space test and passive avoidance learning test, cornu Ammonis (CA) 1, CA3, and Purkinje neuron counts, and the brain levels of brain-derived neurotrophic factor and postsynaptic density protein-95. However, G-CSF treatment reduced the glial fibrillary acidic protein immunostaining index and brain levels of malondialdehyde, tumor necrosis factor-alpha, nuclear factor kappa-B, and lactate. In addition, on MR spectroscopy, G-CSF had a reversible effect on brain lactate levels. In this first designed brain irradiation animal model, which evaluated G-CSF effects, we observed that G-CSF had reparative, neuroprotective and anti-neurodegenerative effects and had increased neurotrophic factor expression, neuronal counts, and morphology changes. In addition, G-CSF had a proven lactate-lowering effect in MR spectroscopy and brain materials.

Antioxidant and hepatoprotective activities of methanolic extract of Fimbristylis miliacea (L.) Vahl

BackgroundFimbristylis miliacea (Cyperaceae) is a grass like herb, widely used in traditional medicine. In our previous study, this plant demonstrated promising in vitro antioxidant activities. The present work evaluated antioxidant and hepatoprotective activities of methanolic extract of F. miliacea through in vivo studies. MethodsThe overall study was structured involving CCl4 toxicant mice model for antioxidant and hepatoprotective effects. Three different doses of 100, 200 and 400 mg/kg.bw were administered to mice. HPLC-DAD was performed for chemical characterization of methanolic extract of F. miliacea. ResultsMethanolic extract of F. miliacea increased superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and decreased malondialdehyde (MDA) level in liver, kidney and brain. Concentrations of liver marker enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and bilirubin in serum were also reduced and restored to normal level after extract administration. Liver histopathology showed recovery of hepatocellular injury after administration of plant extract. In HPLC, ten polyphenolic compounds were detected including caffeic acid and kaempferol, both at high concentrations. ConclusionThe study indicated that F. miliacea has antioxidant and hepatoprotective potentials and contains potential bioactive compounds.

Torasemide Improves the Propionic Acid-Induced Autism in Rats: A Histopathological and Imaging Study.

Autism spectrum disorder is a neurodevelopmental disease in which impaired social behaviors, impaired sociality, and restricted and repetitive behaviors are seen. Bumetanide is a loop diuretic that inhibits Na+-K+-2Cl- cotransporter 1 and it is currently used in clinical phase studies in patients with autism spectrum disorder. In present research, it is purposed to demonstrate the beneficial effects of torasemide which is another Na+-K+-2Cl- cotransporter 1 inhibitor on an experimental autism model induced with propionic acid by providing imaging and brain tissue investigations. Male Wistar rats were used in the present study (n = 30). Propionic acid of 250 mg/kg/day was administrated intraperitoneally in rats to induce autism for 5 days. Three groups were created for present study as follows: group 1, normal control (n = 10); group 2, propionic acid and saline given group (n = 10); group 3, propionic acid + tora-semide-administrated group (n = 10). Torasemide group scored higher on behavioral tests compared to saline group. The brain levels of malondialdehyde, tumor necrosis factor-alpha, interleukin-2, interleukin-17, and Nuclear Factor kappa B (NF-κB), Glial fibrillary acidic protein (GFAP) were remarkably higher in propionic acid + saline group. In histopathology assessments, torasemide group had higher neuronal count of Cornu Ammonis 1, neuronal count of Cornu Ammonis 2 in hippocampus, and Purkinje cells in cerebellum. GFAP immunostaining index (Cornu Ammonis 1) and cerebellum were lower in torasemide group. Magnetic resonance spectroscopy revealed that mean lactate value was higher in propionic acid + saline group compared to torasemide group. Our experimental results showed that torasemide might enhance gamma-aminobutyric acid activity. Torasemide can be considered another promising Na+-K+-2Cl- cotransporter 1 inhibitor in the treatment of autism with a longer half-life and less side effects after further studies.

Alpha-Mangostin Attenuates Oxidative Stress and Apoptosis in Scopolamine-Induced Amnesic Rat Brains

The extract from Garcinia mangostana L. pericarp was reported to scavenge radicals, inhibit acetylcholinesterase (AChE) activity, and improve spatial memory in scopolamine (SCOP)-induced amnesic rats. This study investigated α-mangostin (α-MG) neuroprotective effects against SCOP-induced neurotoxicity.The compound was evaluated for anti-AChE and antioxidant properties in vitro, and its preventive effect on apoptosis and oxidative stress in SCOP-treated rat brains. AChE inhibitory property of α-MG was assessed by fast blue B (FB) salt and β-naphthyl acetate (NA) and Ellman’s assays. The antioxidant properties of α-MG were assessed by ferric reducing antioxidant power (FRAP), scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH), and 2,2′-azino-bis-[3-ethylbenzothiazoline-6-sulfonic acid] (ABTS•+) radicals. Brain levels of malondialdehyde (MDA), lipid peroxidation marker, and activities of the caspase-3 enzyme, an apoptosis-related marker, were determined in SCOP-treated rats pretreated with donepezil (DPZ) and α-MG. IC50 of α-MG and DPZ for AChE activity were 64.23±0.22 and 32.46±0.14 mg/mL, respectively. α-MG and DPZ (100-600 µg/mL) gave FRAP values within the range of 20-410 µmol Fe2+/L. The IC50 of α-MG and DPZ for ABTS were 21.52±3.45 and 14.53±1.86 µg/mL, and for DPPH were 38.12±8.36 and 29.44±5.13 µg/mL, respectively. Prior given to SCOP-induced rats, DPZ and α-MG (50 and 100 mg/kg) reduced MDA levels, and pretreatment of DPZ and α-MG (50 mg/kg), but not α-MG (100 mg/kg), attenuated the increase of caspase-3 activity in cerebral cortex and hippocampus (P&lt;0.05), but not in the basal forebrain. The present study is the first report of α-MG as a potential neuroprotective candidate, and its mechanism might be involved in ameliorating scopolamine-induced neurotoxicity via inhibition of lipid peroxidation and caspase-3 enzyme activity in the cerebral cortex and hippocampus.

Potential Antioxidant Activity of Apigenin in the Obviating Stress-Mediated Depressive Symptoms of Experimental Mice.

This study aimed to examine the antidepressant properties of apigenin in an experimental mouse model of chronic mild stress (CMS). Three weeks following CMS, albino mice of either sex were tested for their antidepressant effects using the tail suspension test (TST) and the sucrose preference test. The percentage preference for sucrose solution and the amount of time spent immobile in the TST were calculated. The brain malondialdehyde (MDA) levels, catalase activity, and reduced glutathione levels were checked to determine the antioxidant potential of treatments. When compared to the control, animals treated with apigenin during the CMS periods showed significantly shorter TST immobility times. Apigenin administration raised the percentage preference for sucrose solution in a dose-dependent manner, which put it on par with the widely used antidepressant imipramine. Animals treated with apigenin displayed a significantly (p ˂ 0.05) greater spontaneous locomotor count (281) when compared to the vehicle-treated group (245). Apigenin was also highly effective in significantly (p ˂ 0.01) lowering plasma corticosterone levels (17 vs. 28 µg/mL) and nitrite (19 vs. 33 µg/mL) produced by CMS in comparison to the control group. During CMS, a high dose (50 mg/kg) of apigenin was given, which greatly increased the reduced glutathione level while significantly decreasing the brain's MDA and catalase activity when compared to the control group. As a result, we infer that high doses of apigenin may have potential antidepressant effects in animal models via various mechanisms.