Brain Lipid Peroxidation Research Articles

DNA Damage and Antioxidant Defence Responses in The Brain and Liver Tissues of Rainbow Trout Infected With Different Bacteria

Fish farming provides food and livelihood for many people around the world. The fact that trout is produced in many parts of the world and has a very rich content in terms of nutritional value increases the importance of trout. However, there are many problems in trout production due to bacterial factors, making fish production extremely difficult. Bacterial factors cause significant fish deaths and economic losses such as slowdown in growth. In addition to these, these factors also cause some damage to the DNA of fish and the formation of oxidations by disrupting the balance of free radicals in the tissues. Therefore, in this study; In the trout farms in our province, the trout with the main bacterial agents causing infection were determined and bacterial species (Staphylococcus epidermidis, Lactococcus garvieae and Bacillius subtilis) were determined by PCR. The brain and liver tissues of these fish were taken and the changes in antioxidant enzyme levels (SOD, CAT, GSH-Px), lipid peroxidation (MDA) and damage to their DNA (8-OHdG) compared to the control groups were investigated. In the study, it was determined that the antioxidant defense system enzyme levels in all three species of bacteria decreased in tissues, while lipid peroxidation and 8-OHdG levels increased.
 As a result; Staphylococcus epidermidis, Lactococcus garvieae and Bacillius
 subtilis bacteria caused changes in antioxidant enzyme levels, lipid peroxidation and 8-OHdG levels in trout brain and liver tissues.

Effect of Selenium on the Iron Homeostasis and Oxidative Damage in Brain and Liver of Mice.

Selenium is an essential trace element that maintains normal brain function, mainly due its antioxidant properties. Although the amount of Se in the body is tightly regulated by the liver, both an excess of and deficiency in Se can modulate the cellular redox status and affect the homeostasis of other essential elements for both humans and animals. The aim of this study was to determine the effect of inorganic selenium excess on oxidative stress and iron homeostasis in brain and liver of laboratory BALB/c mice, which were supplemented with Na2SeO3 solution (0.2 mg and 0.4 mg Se/kg body weight) for 8 weeks. The content of the lipid peroxidation product malondialdehyde and antioxidant enzyme catalase activity/gene expression were used as markers of oxidative damage and were evaluated by spectrophotometric assays. Selenium and iron concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS). Catalase gene expression was analyzed by qRT-PCR and ΔΔCt methods. Our results showed that doses of 0.2 mg Se and 0.4 mg Se caused a relatively low accumulation of Se in the brain of mice; however, it induced a 10-fold increase in its accumulation in the liver and also increased iron accumulation in both tested organs. Both doses of Se increased the content of malondialdehyde as well as decreased catalase activity in the liver, while the 0.4 mg Se dose has also activated catalase gene expression. Brain of mice exposed to 0.2 mg Se showed reduced lipid peroxidation; however, the exposure to 0.4 mg of Se increased the catalase activity as well as gene expression. One may conclude that exposure to both doses of Se caused the accumulation of this micronutrient in mice brain and liver and have also provided a disrupting effect on the levels of iron. Both doses of Se have triggered oxidative liver damage. In the brain, the effect of Se was dose dependent, where −0.2 mg of Se provided antioxidant activity, which was observed through a decrease in lipid peroxidation. On the contrary, the 0.4 mg dose increased brain catalase activity as well as gene expression, which may have contributed to maintaining brain lipid peroxidation at the control level.

Discovering the Effects of Fisetin on NF-κB/NLRP-3/NRF-2 Molecular Pathways in a Mouse Model of Vascular Dementia Induced by Repeated Bilateral Carotid Occlusion.

Vascular dementia (VaD) is the second leading cause of dementia. The majority of VaD patients have cognitive abnormalities, which are caused by cerebral hypoperfusion-induced ischemia, endothelial dysfunction, oxidative stress, and neuroinflammation. Natural products are receiving increasing attention for the treatment of neuroinflammatory diseases. The aim of this study was to investigate the molecular pathways underlying the protective effects of fisetin, a flavonoid present in many fruits and vegetables, in a mouse model of VaD induced by repeated ischemia-reperfusion (IR) of the total bilateral carotid artery. Here, we found that VaD caused brain injury, lipid peroxidation, and neuronal death in the hippocampus, as well as astrocyte and microglial activation, and reduced BDNF neurotrophic factor expression together with behavioral alterations. In addition, VaD induced the activation of inflammasome components (NLRP-3, ASC, and caspase 1), and their downstream products (IL-1β and IL-18) release and promote activation of apoptotic cell death. Fisetin attenuated histological injury, malondialdehyde levels, inflammasome pathway activation, apoptosis, as well as increased BDNF expression, reduced astrocyte, microglial activation, and cognitive deficits. In conclusion, the protective effects of fisetin could be due to the inhibition of the ROS-induced activation of NF-κB/NLRP3 inflammasome together with the activation of antioxidant Nrf2/HO-1, suggesting a possible crosstalk between these molecular pathways.

Protective effects of Buxus hyrcana against memory impairment and oxidative stress in a pentylenetetrazole-kindled epileptic rat model

Pentylenetetrazole (PTZ) is a chemical substance which is largely used for the induction of seizure and epilepsy in the animal model, and it can also, disrupts free radicals balance and cause oxidative stress in the body with a negative impact on memory and learning. In this study, the medicinal plant Buxus hyrcana, was used to evaluate its effect on oxidative stress and memory deficit caused by PTZ in the rats. Twenty-four rats were randomly allocated to 4 groups: control negative under treatment with PTZ (sub-threshold dose 35 mg/kg for one month), control positive under treatment with phenobarbital (PB-30 mg/kg), and two PTZ groups under treatment with B. hyrcana extract (BHE-300, and -600 mg/kg). Standard passive avoidance test was used to evaluate retention and recall (evaluation of memory and learning). After behavioral evaluation, rats were anesthetized, brains were removed, and following preparation of brain homogenates, oxidative stress was evaluated using specified methods. Step-through latency in passive avoidance test in the BHE receiving group was greater than PTZ group (p<0.001). In addition, brain lipid peroxidation malondialdehyde (MDA) and nitric oxide (NO) level in BHE-treated group was significantly lower (p<0.001) and the reduced glutathione (GSH) activity levels were significantly greater versus PTZ group (p<0.001). Our results showed that BHE could prevent memory deficit and ameliorate oxidative stress in the PTZ-kindled rats.

Protective effects of Buxus hyrcana against memory impairment and oxidative stress in a pentylenetetrazole-kindled epileptic rat model

Pentylenetetrazole (PTZ) is a chemical substance which is largely used for the induction of seizure and epilepsy in the animal model, and it can also, disrupts free radicals balance and cause oxidative stress in the body with a negative impact on memory and learning. In this study, the medicinal plant Buxus hyrcana, was used to evaluate its effect on oxidative stress and memory deficit caused by PTZ in the rats. Twenty-four rats were randomly allocated to 4 groups: control negative under treatment with PTZ (sub-threshold dose 35 mg/kg for one month), control positive under treatment with phenobarbital (PB-30 mg/kg), and two PTZ groups under treatment with B. hyrcana extract (BHE-300, and -600 mg/kg). Standard passive avoidance test was used to evaluate retention and recall (evaluation of memory and learning). After behavioral evaluation, rats were anesthetized, brains were removed, and following preparation of brain homogenates, oxidative stress was evaluated using specified methods. Step-through latency in passive avoidance test in the BHE receiving group was greater than PTZ group (p<0.001). In addition, brain lipid peroxidation malondialdehyde (MDA) and nitric oxide (NO) level in BHE-treated group was significantly lower (p<0.001) and the reduced glutathione (GSH) activity levels were significantly greater versus PTZ group (p<0.001). Our results showed that BHE could prevent memory deficit and ameliorate oxidative stress in the PTZ-kindled rats.

Protective effects of Buxus hyrcana against memory impairment and oxidative stress in a pentylenetetrazole-kindled epileptic rat model

Pentylenetetrazole (PTZ) is a chemical substance which is largely used for the induction of seizure and epilepsy in the animal model, and it can also, disrupts free radicals balance and cause oxidative stress in the body with a negative impact on memory and learning. In this study, the medicinal plant Buxus hyrcana, was used to evaluate its effect on oxidative stress and memory deficit caused by PTZ in the rats. Twenty-four rats were randomly allocated to 4 groups: control negative under treatment with PTZ (sub-threshold dose 35 mg/kg for one month), control positive under treatment with phenobarbital (PB-30 mg/kg), and two PTZ groups under treatment with B. hyrcana extract (BHE-300, and -600 mg/kg). Standard passive avoidance test was used to evaluate retention and recall (evaluation of memory and learning). After behavioral evaluation, rats were anesthetized, brains were removed, and following preparation of brain homogenates, oxidative stress was evaluated using specified methods. Step-through latency in passive avoidance test in the BHE receiving group was greater than PTZ group (p<0.001). In addition, brain lipid peroxidation malondialdehyde (MDA) and nitric oxide (NO) level in BHE-treated group was significantly lower (p<0.001) and the reduced glutathione (GSH) activity levels were significantly greater versus PTZ group (p<0.001). Our results showed that BHE could prevent memory deficit and ameliorate oxidative stress in the PTZ-kindled rats.

Fenpyroximate induced cytotoxicity and genotoxicity in Wistar rat brain and in human neuroblastoma (SH-SY5Y) cells: Involvement of oxidative stress and apoptosis

Fenpyroximate (FEN) is an acaricide used in agriculture / horticulture to control spider mites and leafhoppers. It inhibits the transport of mitochondrial electrons at the level of NADH-coenzyme Q oxidoreductase (complex I). Despite the implication of inhibition of mitochondrial complex I in neurotoxicity, especially in neurodegenerative diseases, data concerning FEN neurotoxicity remain limited. Thus, the present study was designed to investigate the toxic effect of FEN on rat brain tissue and on human neuroblastoma cells (SH-SY5Y). Rat exposure to FEN at three different doses (4.8, 9.6 and 48 mg / Kg bw) for 28 consecutive days resulted in histopathological modifications in brain tissue and a significant decrease in acetylcholinesterase activity. Further, FEN significantly enhanced lipid peroxidation and protein oxidation in rat brain and disturbed activities of antioxidant enzymes (SOD, CAT, GPx, and GST). Besides, FEN was found to induce DNA damage in a significant and dose-dependent manner in rat brain as assessed by the comet assay. To better understand FEN neurotoxic effect, we monitored our study on SH-SY5Y cells. We confirm our data found in rat brain tissue. In fact, FEN induced cell mortality in a concentration dependent manner. It over-produced intracellular ROS and lipid peroxidation and enhanced SOD and CAT activities. FEN was also found to induce DNA damage in SH-SY5Y cells. Moreover, FEN induced a loss of mitochondrial membrane potential, which confirms FEN mitochondrial impairing activity. Acridine Orange-Bromure Etidium (AO-BE) cell staining indicated that FEN enhanced the percentage of apoptotic cells in a concentration dependent manner. Further, pretreatment with a general caspases inhibitor (ZVAD-FMK), reduced significantly the FEN induced cell mortality. We also shown that FEN increased caspase 3 activity. These findings suggested, for the first time, the possibility of the involvement of mitochondrial pathway in FEN-induced cell apoptosis.

Hydroxychloroquine attenuated motor impairment and oxidative stress in a rat 6-hydroxydopamine model of Parkinson’s disease

Purpose Parkinson’s disease (PD) is associated with the destruction of dopaminergic neurons in the substantia nigra (SN). Hydroxychloroquine (HCQ) has the capability to cross the blood–brain barrier and promote a neuroprotective potential. This study evaluated the effects of HCQ on the 6-hydroxydopamine (6-OHDA)-induced PD model in rats. Methods Wistar rats were randomly divided into sham, PD, PD + levodopa and PD + HCQ groups. The PD model was induced by a stereotactic administration of 6-OHDA into the left SN pars compacta (SNpc) and confirmed by rotation and the Murprogo’s tests. HCQ (100 mg/kg, p.o.) and levodopa (12 mg/kg, p.o.) were administered once a day for 21 days. Three weeks after surgery, the behavioral tests were performed. Brain lipid peroxidation index (MDA), glutathione peroxidase activity (GPx), total antioxidant capacity (TAC) levels and α-synuclein protein expression in the SN were also measured. Results The behavioral tests demonstrated that induction of PD increased the muscle rigidity and the number of rotations, which were reversed by HCQ treatment. Also, induction of PD was associated with an increase in α-synuclein protein levels and MDA and decreased TAC levels and GPx activity. However, HCQ decreased α-synuclein and MDA levels while increased TAC levels and GPx activity. In addition, histopathological data showed that HCQ protects dopaminergic neurons against 6-OHDA-induced toxicity. Conclusion According to the results, HCQ has a beneficial effect in improving PD-related pathophysiology, in part, by mitigating oxidative stress and protecting the dopaminergic neurons in the SN.

Time Course of Neurobehavioral Disruptions and Regional Brain Metabolism Changes in the Rotenone Mice Model of Parkinson's Disease.

Parkinson’s disease (PD) is characterized by slow progression with a long prodromal stage and the gradual evolution of both neuropsychological symptoms and subtle motor changes, preceding motor dysfunction. Thus, in order for animal models of PD to be valid, they should reproduce these characteristics of the disease. One of such models, in which neuropathology is induced by chronic injections of low doses of mitochondrial toxin rotenone, is well established in rats. However, data on this model adapted to mice remain controversial. We have designed the study to describe the timecourse of motor and non-motor symptoms during chronic subcutaneous administration of rotenone (4 mg/kg daily for 35 days) in C57BL/6 mice. We characterize the underlying neuropathological processes (dopaminergic neuron degeneration, regional brain metabolism, monoamine neurotransmitter and lipid peroxidation changes) at different timepoints: 1 day, 2 weeks and 5 weeks of daily rotenone exposure. Based on the behavioral data, we can describe three stages of pathology: cognitive changes from week 2 of rotenone exposure, subtle motor changes in week 3–4 and motor dysfunction starting roughly from week 4. Neuropathological changes in this model include a general decrease in COX activity in different areas of the brain (acute effect of rotenone) and a more specific decrease in midbrain (chronic effect), followed by significant neurodegeneration in SNpc but not VTA by the 5th week of rotenone exposure. However, we were unable to find changes in the level of monoamine neurotransmitters neither in the striatum nor in the cortex, nor in the level of lipid peroxidation in the brainstem. Thus, the gradual progression of pathology in this model is linked with metabolic changes, rather than with oxidative stress or tonic neurotransmitter release levels. Overall, this study supports the idea that a low-dose rotenone mouse model can also reproduce different stages of PD as well as rats.

Effect of MCI-186 on Lipid Peroxidation in Experimental Traumatic Brain Damage in Rats.

Brain damage occurs in many clinical conditions, including trauma, ischemia, and hypertension. Reactive oxygen products and lipid peroxidation are responsible for the brain damage that occurs in these clinical conditions. We investigated whether MCI-186 (3-methyl-1-phenyl-2-pyrazoline-5-one), a free radical binding agent on lipid peroxidation, affects malondialdehyde (MDA), glutathione (GSH), and glutathione peroxidase (GPx) levels in traumatic brain damage. The traumatic brain damage model, modified by Feeney, was performed on 28 male Wistar rats separated into 4 groups. The MDA, GSH, and GPx levels in the brain tissues of each group were studied. MDA levels in the traumatized group were significantly higher than those in the sham and MCI-186 groups (p<0.05), while GSH levels were significantly higher in the sham group than in the trauma and solvent groups (p<0.05). No significant difference was observed between the sham and MCI-186 groups (p>0.05). Although the average GPx level was higher in the sham and MCI-186 groups, no significant difference was found between groups. Reactive oxidation products significantly decreased in the MCI-186 group. Thus, MCI-186 can be used as a free radical-binding agent in traumatic brain damage.

PROTECTIVE ROLE OF BACOSIDE A ON BLOOD BRAIN BARRIER INTEGRITY

Oxidative stress induced loss of neuronal function with age is related to disruption of the blood brain barrier (BBB)integrity. The protective effect of Bacopa monnieri in combating oxidative stress induced dysfunction of BBB is being studied. We extracted, isolated and quantified bacoside A from bacopa leaf powder. An invivo trial was conducted in rats, which were treated with two doses of Bacoside A (200 and 400 mg/kg BW), through intra-peritoneal route for 7 consecutive days and the efficacy of the treatment was tested by studying the integrity of BBB using Evan’s Blue (EB) dye extravasation, antioxidant enzyme activity and Lipid peroxidation and expression of tight junction (TJ) protein occludin and ROS induced factor Nrf2in the brain. Bacoside A treatment for 7 days resulted in a dose dependent significant (p&lt;0.001) decrease in concentration of EB into the brain indicative of minimum disruption in BBB integrity compared to control rats. Similarly, bacoside A significantly (p&lt;0.001) increased the activity of antioxidant enzymes viz. SOD, catalyse and GPx, with a concomitant significant (p&lt;0.001) decrease in lipid peroxidation in brain. Further, a small dose depended increase in the relative mRNA expression of occludin and Nrf2 was observed in brain of rats treated with bacoside A. Hence, it is concluded that the beneficial effect of Bacoside A in restoring integrity of BBB could be associated with the increased expression TJ protein occludin and ROS induced transporter Nrf2 that might have strengthened the TJ and minimized ROS induced damage of the BBB.

Memory improvement effects of Ganoderma mediosinense in mice via its anticholinergic and antioxidant activities

AbstractBackgroundSpecies of the genus Ganoderma are valued both for their medicinal as well as nutritional properties. Traditionally, these are employed in neurological disorders. However, G. mediosinense has not been evaluated for anti‐amnesic effects previously. Therefore the present study is aimed to explore the cognitive improvement effects of the G. mediosinense extract (GME) against mouse model of scopolamine induced amnesia.MethodAnimals were orally administered with GME (200, 400 and 800 mg/kg) for 7 consecutive days and amnesia was induced by scopolamine (1 mg/kg, i.p.) after 30 min of treatment. Cognitive functions were determined by employing passive shock avoidance task and novel object recognition test. Brain AChE and lipid peroxidation were determined to have an insight into the associated neuroprotective mechanism of GME.ResultTreatment with GME showed dose dependent amelioration of cognitive deficit induced by scopolamine in animals. Also, GME reduced the brain AChE activity and oxidative stress.ConclusionThese results indicated the anti‐amnesic effects of GME via decreasing brain cholinergic and oxidative stress.

Effects of New Galantamine Derivatives in a Scopolamine Model of Dementia in Mice.

Alzheimer's disease (AD), a progressive neurodegenerative disorder characterized by memory loss and cognitive functions decline, is a leading cause for dementia and currently ranked as the sixth foremost cause of death. As of present, treatment of AD is symptomatic without convincing therapeutic benefits and new, effective, therapeutic agents are pursued. Due to massive loss of cholinergic neurons and decreased acetylcholine levels, cholinesterase inhibitors like galantamine, remain the backbone of pharmacological treatment of the disease. In the present study, using behavioral and biochemical methods, four newly synthesized galantamine derivatives, Gal 34, Gal 43, Gal 44, and Gal 46, were evaluated for a beneficial effect in a scopolamine model of dementia in mice. They were designed to have all the advantages of galantamine and additionally to inhibit β-secretase and exert favorable effects on plasma lipids. Behavioral tests included step-through inhibitory avoidance, T-maze, and the hole-board test, whereas biochemical evaluations involved assessment of acetylcholinesterase activity, brain monoamines levels, lipid peroxidation, catalase, glutathione peroxidase, and superoxide dismutase activities along with measurement of total glutathione. Results show that Gal 43, Gal 44, and, in particular, Gal 46 are especially effective in improving both short- and long-term memory and in the case of Gal 46 having a significant effect on exploratory activity as well. Although Gal 34 did not show behavioral effects as convincing as those of the other three galantamine derivatives, it demonstrated persuasive antioxidant and restorative capacities, making all four galantamine derivatives promising AD treatment agents and prompting further research, especially that in many of our studies they performed better than galantamine.

Brain Levels of Reduced Glutathione and Malondialdehyde in Honey-Fed Wistar Rats

This research sought to verify the effect of natural honey on brain levels of malondialdehyde (MDA) and reduced glutathione (GSH) in rats. Forty nine male and female Wistar rats were used for the experiment. The rats were allotted into seven groups of seven rats in each group. For one month, rats in groups 1-4 were fed with 100% feed, 20%, 30% and 40% honey respectively. The remaining 3 groups were fed with amounts of refined fructose and glucose equivalent to those in 20%, 30% and 40% honey. The brains were then excised, homogenized and used for biochemical analysis. Results showed that honey in all concentrations caused a significant increase in GSH levels but only 20% honey caused a significant decrease in MDA level when compared with control. Also, fructose feeding at 20%, 30% and 40% increased both brain GSH and MDA levels. Consequently, the influence of GSH as an antioxidant against brain lipid peroxidation needs further studies for better understanding since an increase in GSH for fructose- and honey-fed rats did not cause a simultaneous decrease in MDA content.

Lacidipine Attenuates Symptoms of Nicotine Withdrawal in Mice.

Nicotine-withdrawal after daily exposure manifests somatic and affective symptom including a range of cognitive deficits. Earlier studies suggested participation of L-type calcium channels (LTCCs) in development of nicotine dependence and expression of withdrawal signs. An upsurge in Ca2+-induced oxidative stress in brain underlies the biochemical events and behavioral signs of nicotine-withdrawal. The present study is aimed to explore the effects of lacidipine (LTCC antagonist) against nicotine-withdrawal. Swiss albino mice were administered ( -)-nicotine hydrogen tartrate (3.35mg/kg, t.i.d.) from days 1 to 7 and alongside lacidipine (0.3, 1, and 3mg/kg, i.p.) given from days 1 to 14. Somatic withdrawal signs were noted 48h after last dose of nicotine. Bay-K8644 (LTCC agonist) was administered in mice subjected to nicotine-withdrawal and lacidipine (3mg/kg) treatments. Behavioral tests of memory, anxiety, and depression were conducted on days 13 and 14 to assess the effects of lacidipine on affective symptoms of nicotine-withdrawal. Biomarkers of oxido-nitrosative were quantified in the whole brain. Nicotine-withdrawal significantly enhanced somatic signs and symptoms of anxiety, depression, and memory impairment in mice. Lacidipine (1 and 3mg/kg) attenuated nicotine-withdrawal induced somatic symptoms and also ameliorated behavioral abnormalities. Nicotine-withdrawal triggered an upsurge in brain lipid peroxidation, total nitrite content, and decline in antioxidants, and these effects were attenuated by lacidipine. Bay-K8644 significantly abolished improvement in somatic and affective symptoms, and antioxidant effects by lacidipine in mice subjected to nicotine-withdrawal. Lacidipine mitigated nicotine-withdrawal triggered somatic and affective symptoms owing to decrease in brain oxido-nitrosative stress.

Evaluation of cholinesterase inhibitory and antioxidant activity of Wedelia chinensis and isolation of apigenin as an active compound

BackgroundWedelia chinensis has been reported as a folk medicine for the treatment of different diseases including neurodegenerative disease. Although the plant has been studied well for diverse biological activities, the effect of this plant in neurological disorder is largely unknown. The present study was undertaken to evaluate the cholinesterase inhibitory and antioxidant potential of W. chinensis.MethodsThe extract and fractions of the plant were evaluated for acetylcholinesterase and butyrylcholinesterase inhibitory activity by modified Ellman method. The antioxidant activity was assessed in several in vitro models/assays such as reducing power, total antioxidant capacity, total phenolic and flavonoid content, scavenging of 2,2′-diphenyl-1-picrylhydrazyl (DPPH) free radical and hydroxyl radical, and inhibition of brain lipid peroxidation. Chromatographic and spectroscopic methods were used to isolate and identify the active compound from the extract.ResultsAmong the fractions, aqueous fraction (AQF) and ethylacetate fraction (EAF) exhibited high inhibition against acetylcholinesterase (IC50: 40.02 ± 0.16 μg/ml and 57.76 ± 0.37 μg/ml) and butyrylcholinesterase (IC50: 31.79 ± 0.18 μg/ml and 48.41 ± 0.05 μg/ml). Similarly, the EAF and AQF had high content of phenolics and flavonoids and possess strong antioxidant activity in several antioxidant assays including DPPH and hydroxyl radical scavenging, reducing power and total antioxidant activity. They effectively inhibited the peroxidation of brain lipid in vitro with IC50 values of 45.20 ± 0.10 μg/ml and 25.53 ± 0.04 μg/ml, respectively. A significant correlation was observed between total flavonoids and antioxidant and cholinesterase inhibitory activity. Activity guided chromatographic separation led to the isolation of a major active compound from the EAF and its structure was elucidated as apigenin by spectral analysis.ConclusionsThe potential ability of W. chinensis to inhibit the cholinesterase activity and peroxidation of lipids suggest that the plant might be useful for the management of AD.

Imidazole antifungal drug clotrimazole alters the behavior, brain acetylcholinesterase and oxidative stress biomarkers in African catfish Clarias gariepinus (Burchell 1822)

This study was carried out to determine the effect of clotrimazole (CTZ), an imidazole fungicide on behavior, brain acetylcholinesterase, lipid peroxidation and oxidative stress parameters in Clarias gariepinus juveniles. Fish were acutely exposed to five nominal concentrations of CTZ and control to assess the behavioral effects on fish. To determine the effects on brain acetylcholinesterase, lipid peroxidation and oxidative stress parameters, fish were exposed to three sub-lethal concentrations vis 7.76, 3.89 and 1.94 mg/L which corresponds to 20 10 and 5% of 96 h LC50 value of CTZ respectively and a control for 21 days and allowed to recover for 7 days. The brain, liver and gills were sampled weekly. Fish exposed to different concentrations of the drug displayed behavioral responses such as reduced swimming rate, mucus secretion, decrease in both the feeding frequency and rate. A duration dependent increase in the levels of brain acetylcholinesterase was observed among the exposed groups. The result of the sub-lethal exposure revealed concentration and duration significant increase in lipid peroxidation (LPO), catalase activity (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione reductase (GR) and glutathione peroxide (GPx) in both the liver and gill tissues of the exposed groups compared to the control. The effects of the drug on many of the observed parameters did not wane after the 7-day withdrawal period. This study revealed that CTZ has a negative impact on the observed parameters, thus providing additional evidence of its toxic effect on non-target aquatic species, especially fish.

Antidementia Effects of Alternanthera philoxeroides in Ovariectomized Mice Supported by NMR-Based Metabolomic Analysis.

The crude ethanol extract of the whole plant of Alternanthera philoxeroides (Mart.) Griseb was investigated for its potential as antidementia, induced by estrogen deprivation, based on in vitro antioxidant activity, β-amyloid aggregation inhibition and cholinesterase inhibitory activity, as well as in vivo Morris water maze task (MWMT), novel object recognition task (NORT), and Y-maze task. To better understand the effect of the extract, oxidative stress-induced brain membrane damage through lipid peroxidation in the whole brain was also investigated. Additionally, expressions of neuroinflammatory cytokines (IL-1β, IL-6 and TNF-α) and estrogen receptor-mediated facilitation genes such as PI3K and AKT mRNA in the hippocampus and frontal cortex were also evaluated. These effects were confirmed by the determination of its serum metabolites by NMR metabolomic analysis. Both the crude extract of A. philoxeroides and its flavone constituents were found to inhibit β-amyloid (Aβ) aggregation.

Antioxidant activities of ethanolic extract of Annona muricata against different pro-oxidant induced lipid peroxidation in rat brain and liver

Antioxidant activities of ethanolic extract of Annona muricata against different pro-oxidant induced lipid peroxidation in rat brain and liver

Effect of Piracetam on Brain Oxidative Stress and Tissue Damage Following Toluene Exposure in Rats

In this study, the effect of the nootropic drug piracetam on brain oxidative stress and histopathological changes in brain, liver and kidney following exposure to toluene in rats was examined. Piracetam (150 or 300 mg/kg, subcutaneously, daily) was given along with toluene (500 mg/kg, intraperitoneally, daily) for one week. The brain content of malondialdehyde (MDA), reduced glutathione (GSH) and the activity of paraoxonase-1 (PON-1), and butyrylcholinesterase (BChE) in brain homogenates were determined. Histopathology of the brain, liver and kidney and brain Bax immunohistochemistry were performed. Results showed that exposure to toluene resulted in increased brain lipid peroxidation (MDA) and NO along with decreased reduced glutathione. Toluene also inhibited PON-1, and BChE activities. The administration of piracetam had no significant effect on brain lipid peroxidation. The level of reduced glutathione was unchanged by piracetam but PON1 activity was increased by the lower dose of the drug. Piracetam showed no significant effect on BChE activity in toluene treated rats. Histopathological examination of the brain of toluene only treated rats showed degenerated neurons in cerebral cortex, marked neuronal vacuolation in hippocampus and focal hemorrhage. Bax 3 immunohistochemical staining showed cytoplasmic reactivity in degenerated neurons. Rats given piracetam showed decreased cortical cellularity, increased number of degenerated neurons and increased BAX staining. The higher dose of the drug caused sinusoidal hemorrhage and intertubular hemorrhage in kidney. Collectively, these results indicate that treatment with piracetam wan not able to decrease neuronal damage in rats exposed to toluene.