Brain Malondialdehyde Research Articles

Lutein Exerts Antioxidant and Neuroprotective Role on Schizophrenia-Like Behaviours in Mice.

Schizophrenia is an esteemed neuropsychiatric condition delineated by the manifestation which role of the N-methyl-D-aspartate receptor (NMDAR) is important. Lutein administration exhibits protective effects via NMDA receptors. Thus, the main goal of this research was to investigate how lutein can possibly act as an antioxidant and provide protection for the brain against schizophrenia-like behaviours in mice. In total, 24 male mice were divided into four experimental groups: control, ketamine (20 mg/kg, i.p), lutein (10 mg/kg, i.p) and a mix of ketamine (20 mg/kg, i.p) and lutein (10 mg/kg, i.p). Lutein was given to the mice for 30 days, while ketamine was given from Days 16 to 30 to create a model of schizophrenia in the animals. After giving drugs, schizophrenia-like behaviours were evaluated with novel object recognition test (NORT), tail suspension test (TST), forced swimming test (FST) and open field tests. Furthermore, the amounts of brain malondialdehyde (MDA), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) were assessed. The findings showed a noteworthy decrease in the crossings during the open field test and increase in immobility duration in the TST and FST as a result of ketamine administration (p < 0.05). Prior administration of lutein showed a decrease in the detrimental effects of ketamine on the open field assay, along with a reduction in immobility duration in the TST and FST experiments (p < 0.05). Administration of ketamine caused a notable reduction in the discrimination index, while pretreatment with lutein was associated with a rise in the discrimination index (p < 0.05). Furthermore, the administration of ketamine significantly increased the levels of MDA in both cortical and subcortical regions, which were then reduced by lutein pretreatment (p < 0.05). Moreover, ketamine use led to a significant decrease in tissue SOD, GPx and CAT levels in both cortical and subcortical brain regions in mice (p < 0.05). Nonetheless, lutein pretreatment significantly enhanced SOD, GPx and CAT levels in cortical and subcortical regions (p < 0.05). These results indicate that lutein may have protective effects on the brain to improve behavioural problems.

The possible antioxidative effects of ketogenic diet by modifying brain klotho expression: a rat model study

ABSTRACT Objectives: The ketogenic diet (KD) has long been used as an alternative nonpharmacological therapy to manage pharmacoresistant epilepsy. The anticonvulsant mechanisms of KD have yet to be fully elucidated. The present study explored whether a KD could exert antioxidative effects by altering brain Klotho (Kl) gene expression. Methods: Thirty male rats were divided into three groups: the normal diet (ND) group received standard rat chow; the calorie-restricted diet (CRD) group was maintained at 90% of the calculated energy need; and the KD group received a diet composed of 8% protein, 2% carbohydrates, and 90% fat (per calorie macronutrient). The levels of β-hydroxybutyrate (BHB) in the serum, Kl gene expression in the brain, and Kl protein, malondialdehyde (MDA), and protein carbonyl (PC) levels in the serum and brain were evaluated by standard methods. Results: The serum BHB levels in the KD group were significantly greater than those in the ND and CRD groups (p < 0.001). The Kl expression in the brain was significantly greater in the KD group than in the ND group (p = 0.028). The brain MDA levels in the KD group were significantly lower than those in the ND group (p = 0.006). Elevated BHB was positively correlated with brain Kl expression (r = 0.668, p < 0.001). The brain MDA levels were negatively correlated with brain Kl expression (r = −0.531, p = 0.003) and serum BHB levels (r = 0.472, p = 0.020). Discussion: KD might exert antioxidative effects by increasing BHB and upregulating Kl in the brain. This could be considered a possible anticonvulsant mechanism of KD.

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.

Capsaicin Protects Against Nigrostriatal Neurodegeneration Induced by Rotenone

Capsaicin, the principal pungent ingredient of hot pepper exerts neuroprotective effects. In this study, the effect of capsaicin on rotenone-induced Parkinson’s disease in mice was investigated. Mice were given subcutaneous rotenone injections (1.5 mg/kg, every other day) and at the same time treated with the vehicle, L-dopa (25 mg/kg) or capsaicin at doses of 0.5 or 1.0 mg/kg orally once a day for two weeks. Biochemical indices of oxidative stress, malondialdehyde, reduced glutathione and nitric oxide were determined in brain tissue and histopathological study of the brain was done. Behavioral tests included stair, wire hanging and wood walking tests. Results showed that rotenone treatment led to significant increases in brain malondialdehyde and nitric oxide contents parallel with marked depletion of reduced glutathione. Rotenone induced degeneration of pigmented neurons in substantia nigra and of cerebral cortex and hippocampus neurons. Rotenone impaired neuromuscular strength, motor balance and coordination. Treatment with capsaicin significantly ameliorated the neuronal degeneration caused by rotenone and improved motor function. Capsaicin alleviated the increase in lipid peroxidation (malondialdehyde) and nitric oxide and prevented the depletion of reduced glutathione in brain of rotenone-treated animals. These data indicate that capsaicin protects against rotenone-induced neuronal damage and this involves decreased level of oxidative stress. Capsaicin therefore might prevent cell death in the brain of Parkinson’s disease patients.

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.

Selenium protects against bile duct ligation-induced brain damage in male rats: effect on brain ammonia, glutamine and fos gene expression

ABSTRACT Hepatic encephalopathy (HE) is a severe medical illness often associated with liver cirrhosis and characterized by personality changes, intellectual impairment, and decreased consciousness. The exact pathophysiology of HE is debated, but it generally involves neurotoxins, decreased neurotransmission, systemic inflammation, and altered brain energy utilization. The goal of this study is to find out the protective effect of selenium (Se) supplements on the brains of rats with chronic extrahepatic cholestasis caused by bile duct ligation. Thirty albino rats were divided into three groups. Group I: Sham-operated control; group II: bile duct-ligated rats (BDL); and group III: bile duct-ligated rats protected with selenium (BDL-Se), receiving 100 µg/kg/day of selenium orally for six weeks. Following the experimental period, histological and biochemical analyses of liver and brain tissues were performed after sacrifice. Results elucidated that selenium reduced oxidative stress in the brain, indicated by a reduced level of brain malondialdehyde (MDA), an increased level of brain reduced glutathione (GSH), decreased collagen deposition, as well as the intensity of inflammatory infiltrate in liver tissue, the absence of ruptured blood vessels, and degenerated neurons in brain tissue. Additionally, selenium exhibited an anti-inflammatory role by lowering the brain levels of interleukin-1β (IL-1β) and the c-fos gene.

Synergistic effect of chrysin and kaempferol in ameliorating Cerebral Ischemic Reperfusion injury in rat by controlling expression of proinflammatory mediators NF-κB and STAT3

ABSTRACT Objectives The two flavonoids kaempferol and chrysin are known to possess anti-inflammatory and antioxidant activities. In addition, these two flavonoids were reported to display synergistic effects against inflammation. The present study aims to provide an analysis of the combined effects of kaempferol and chrysin on ischemic rat brain induced by endothelin-1. Methods The neurological deficit score and infarct area of the brain were determined post drug treatment. Histopathological sections displayed the morphological changes in the brain tissue. The brain tissues were processed for assessing the antioxidant and anti-inflammatory activity by measuring superoxide dismutase activity, catalase activity, level of reduced glutathione, brain malondialdehyde, and amount of calcium. The expression level of inflammatory molecules was analyzed by western blotting and immunohistochemistry. Results The infarct area, neurological score and NF-κB and STAT3 expression levels were significantly reduced. Discussion The analysis of neuroprotective synergistic activity of kaempferol and chrysin indicated the therapeutic potential of the combination in alleviating cerebral ischemia by controlling expression of proinflammatory mediators.

Mechanism of acupuncture in attenuating cerebral ischaemia-reperfusion injury based on nuclear receptor coactivator 4 mediated ferritinophagy.

To explore the effect of acupuncture treatment on cerebral ischaemia-reperfusion injury (CIRI) and reveal the underlying mechanism of the effect based on nuclear receptor coactivator 4 (NCOA4) mediated ferritinophagy. Sprague-Dawley male rats were divided into four groups: the sham group, model group, acupuncture group, and sham acupuncture group. After 2 h of middle cerebral artery occlusion (MCAO), reperfusion was performed for 24 h to induce CIRI. The rats were treated with acupuncture at the Neiguan (PC6) and Shuigou (GV26) acupoints. Their neurological function was evaluated by taking their Bederson scores at 2 h after ischaemia and 24 h after reperfusion. Triphenyltetrazolium chloride staining was applied to assess the cerebral infarct volume at 24 h after reperfusion. The malondialdehyde (MDA) and ferrous iron (Fe2+) levels were observed after 24 h of reperfusion using an assay kit. Western blotting was performed to detect the expression of NCOA4 and ferritin heavy chain 1 (FTH1) at 24 h after reperfusion. Moreover, the colocalization of ferritin with neurons, NCOA4 with microtubule-associated protein 1 light chain 3 (LC3), and NCOA4 with ferritin was visualized using immunofluorescence staining. Acupuncture significantly improved neurological function and decreased cerebral infarct volume in the acupuncture group. Following CIRI, the expression of NCOA4, LC3 and FTH1 was increased, which enhanced ferritinophagy and induced an inappropriate accumulation of Fe2+ and MDA in the ischaemic brain. However, acupuncture dramatically downregulated the expression of NCOA4, LC3 and FTH1, inhibited the overactivation of ferritinophagy, and decreased the levels of MDA and Fe2+. Acupuncture can inhibit NCOA4-mediated ferritinophagy and protect neurons against CIRI in a rat model.

Effects of housing conditions on stress, depressive like behavior and sensory-motor performances of C57BL/6 mice

BackgroundThe effects of housing conditions on animal physiology, behavior or stress are still debated. The aim of this study was to investigate the effects of three different housing systems, individually ventilated cages (IVC), classical small cages with floor surface area of 500 cm2 (CC500) and classical large cages with floor surface area of 800 cm2 (CC800) on body weight, sensory-motor performances, depression-like behavior, plasma corticosterone and brain oxidative stress parameters in C57BL/6 mice. The mice housed in one of the cages from birth to 6 months of age. Hang wire and adhesive removal tests were performed to evaluate somatosensory and motor performances. The extent of depression was determined by the forced swim test. Blood corticosterone levels were measured. In addition, brain malondialdehyde (MDA), total antioxidant status (TAS) and total oxidant status (TOS) levels were analyzed.ResultsThe depression-like behavior of the groups was similar. Although there were no significant differences in hang wire test among groups, CC500 group required longer durations in adhesive removal test. The body weight and plasma corticosterone levels of CC800 group were significantly higher than other groups. The oxidative stress parameters were highest in CC500 cage.ConclusionsOur study showed that the least stressful housing condition was IVC cage systems. Interestingly, the number of mice in the classical cages had a significant effect on stress levels and sensory-motor performance.

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.

Faecal Microbiota Transplantation Alleviates Ferroptosis after Ischaemic Stroke

Ischaemic stroke can induce changes in the abundance of gut microbiota constituents, and the outcome of stroke may also be influenced by the gut microbiota. This study aimed to determine whether gut microbiota transplantation could rescue changes in the gut microbiota and reduce ferroptosis after stroke in rats. Male Sprague-Dawley rats (6 weeks of age) were subjected to ischaemic stroke by middle cerebral artery occlusion (MCAO). Fecal samples were collected for 16S ribosomal RNA (rRNA) sequencing to analyze the effects of FMT on the gut microbiota. Neurological deficits were evaluated using the Longa score. triphenyl tetrazolium chloride (TTC) staining was performed in the brain, and kits were used to measure malondialdehyde (MDA), iron, and glutathione (GSH) levels in the ipsilateral brain of rats. Western blotting was used to detect the protein expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and the transferrin receptor 2 (TFR2) in the ipsilateral brain of rats. Stroke induced significant changes in the gut microbiota, and FMT ameliorated these changes. TTC staining results showed that FMT reduced cerebral infarct volume. In addition, FMT diminished MDA and iron levels and elevated GSH levels in the ipsilateral brain. Western blot analysis showed that FMT increased GPX4 and SLC7A11 protein expression and decreased TFR2 protein expression in the ipsilateral brain after stroke. FMT can reverse gut microbiota dysbiosis, reduce cerebellar infarct volume, and decrease ferroptosis after stroke.

Effects of Duloxetine on Oxidant-Antioxidant System in Rat Brain Tissues

Objective: After the relationship between depression and oxidative stress (OS) was demonstrated, the effect of antidepressant drugs on OS has become important. In this study, we aimed to determine the effects of the antidepressant duloxetine on the activities of the superoxide dismutase (SOD), catalase (CAT), adenosine deaminase (ADA), xanthine oxidase (XO) and glutathione peroxidase (GSH-Px) enzymes as well as the lipid peroxidation (LP) product malondialdehyde (MDA) and nitric oxide (NO) levels in rat brains. &#x0D; Material and Method: Twenty male Sprague-Dawley rats were used for the study. The first group was the control group (n=10) and the second group was the duloxetine group (n=10). Duloxetine was administered intragastrically once a day at a dose of 10 mg/kg for two weeks in the second group. Water was administered intragastrically once a day for two weeks in the first group. Rats were sacrificed at the end of the fourteenth day. The brain tissues were collected and then analyzes were performed.&#x0D; Results: As a result of this study, we found that duloxetine increased the SOD (P=0.026) activity and decreased the ADA (P=0.041), XO (P=0.034) and CAT (P=0.006) activities significantly compared to the control group. We also found an increase in the GSH-Px enzyme activity and decrease in the NO and MDA levels at non-significant rates in the duloxetine group brain tissues.&#x0D; Conclusion: The significant increase in the activity of the antioxidant enzyme SOD, the significant decrease in the activities of the XO and ADA enzymes, which can cause the formation of reactive oxygen products in the organism, and the insignificant decrease in the LP indicator MDA suggest that duloxetine can positively change the antioxidant status in rat brain tissues.

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&lt;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&lt;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&lt;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.

The effects of different light spectrum on some oxidative stress parameters in male and female rats

The objective of this study was to investigate oxidative stress parameters in plasma, liver, and brain of Sprague Dawley rats grown under a compact fluorescent lamp with purple, blue, green, yellow, orange, red, and white. For this purpose, 56 male and 56 female rats were housed in standard cages under seven different light colors from weaning until puberty. Malondialdehyde (MDA), glutathione (GSH), and glutathione peroxidase (GPx) in plasma, liver, and brain were examined as oxidative stress parameters. Two factors which are gender and light were investigated regarding the main effects by Two-way ANOVA with the General Linear Model procedure. The different light spectrums had a significant impact on MDA, GSH and, GPx of plasma, liver, and brain (P&lt;0.05). The red group resulted the highest in plasma, liver, and brain MDA. In addition, some of the examined parameters were different for the gender basis. The plasma GSH, the liver MDA, the liver and brain GPx were different in male and female rats (P&lt;0.05). Only the liver GPx enzyme activity was higher in male rats, the other parameters in the female rats had a higher value. In conclusion, low-wavelength lights may be more useful for rats’ environments when compared to high wavelengths in manner oxidative stress. However, illumination is not the sole phenomenon for raising animals. Environmental demands may vary from time to time and even according to gender. Moreover, it may be useful for studies to be conducted by considering other lighting factors such as intensity and cycle.

Mitigating effect of ferulic acid on di-(2-ethylhexyl) phthalate-induced neurocognitive dysfunction in male rats with a comprehensive in silico survey

Di-(2-ethylhexyl) phthalate (DEHP) is the most abundant phthalate threatening public health-induced neurotoxicity. This neurotoxicity is associated with behavioral and biochemical deficits in male rats. Our study investigated the neuroprotective effect of ferulic acid (FA) on male rats exposed to DEHP. Thirty-two male Wistar rats were assigned to four groups. Group I control rats received corn oil, group II intoxicated rats received 300 mg/kg of DEHP, group III received 300 mg/kg of DEHP + 50 mg/kg of FA, and group IV received 50 mg/kg of FA, all agents administrated daily per os for 30 days. Anxiety-like behavior, spatial working memory, and recognition memory were assessed. Also, brain oxidative stress biomarkers, including brain malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), superoxide dismutase (SOD), brain-derived neurotrophic factor (BDNF) as well as heme oxygenase-1 (HO-1) were measured. Moreover, brain histopathology examinations associated with immunohistochemistry determination of brain caspase-3 were also evaluated. Furthermore, docking simulation was adapted to understand the inhibitory role of FA on caspase-3 and NO synthase. Compared to DEHP-intoxicated rats, FA-treated rats displayed improved cognitive memory associated with a reduced anxious state. Also, the redox state was maintained with increased BNDF levels. These changes were confirmed by restoring the normal architecture of brain tissue and a decrement in the immunohistochemistry caspase-3. In conclusion, FA has potent antioxidant and antiapoptotic properties that confirm the neuroprotective activity of FA, with a possible prospect for its therapeutic capabilities and nutritional supplement value.

State of peroxidation in the brain and liver in experimental diabetes and its correction possibility with niacin-oxyethylendiphosphonatogermanate

The development of pharmacological methods to control oxidant stress manifestations in diabetes can be achieved using organic complex germanium compounds. One of the promising compounds is niacin-oxyethylenediphosphonategermanate (MIGU-4), which is an effective corrector of lipid metabolism and a stabilizer of the lipid layer of erythrocyte and hepatocyte membranes in the streptozotocin-induced diabetic model. The aim of the work is to determine the dynamics of the malondialdehyde (MDA) content, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPO) in the brain tissue, as well as the diene conjugate (DC) content, lipid hydroperoxides (LHP), reduced glutathione (GSH) in the liver mitochondria, the serum activities of aspartate and alanine aminotransferases (AST and ALT) in experimental diabetes mellitus with the correction using a complex compound of germanium with nicotinic acid – MIGU-4 and insulin, insulin alone as well as in comparison with effectiveness of vitamin E supplementation. Materials and methods. Diabetes was induced in male Wistar rats by intraperitoneal injection of streptozotocin (60.0 mg/kg). MIGU-4 was administered intraperitoneally at a dose of ED50 that was 25.0 mg/kg. Mitochondrial membranes were obtained by differential centrifugation of the liver tissue. In rats with confirmed diabetes, parameters of peroxidation and antioxidant protection were studied by generally accepted biochemical and biophysical methods. Results. Glucose levels were 29.4 % lower in rats treated with MIGU-4 (25.0 mg/kg) after 8 weeks of streptozotocin-induced diabetes than those in untreated diabetic rats (p &lt; 0.05), while a decrease was 39.0 % (p &lt; 0.05) upon insulin treatment, and 47.2 % (p &lt; 0.05) – with combined use of the drugs. The MDA content in the brain tissue was 3.48 times higher than that in the control (p &lt; 0.05). At the same time, the activities of SOD and CAT were decreased by 46.4 % and 32.0 %, respectively, the activity of GPO was decreased by half (p &lt; 0.05). In the liver mitochondria, the DC content exceeded that in the control by 53.5 % (p &lt; 0.05), and the MDA and LHP levels were 2.48 times and 31.7 % higher (p &lt; 0.05), respectively. AST activity was almost doubled, ALT activity was 5.48 times increased. Insulin and the biologically active substance MIGU-4 used alone exerted a moderate corrective effect. The combined use of the drugs caused definite therapeutic and preventive effects as the brain content of MDA was 2.4 times decreased, the activity of SOD, CAT and GPO was increased by 45.6 %, 35.2 % and 67.3 % (p &lt; 0.05), respectively. In the liver mitochondria, the DC, MDA, and LHP contents were decreased by 41.0 %, 53.3 %, and 28.4 %, respectively, compared to those in rats with diabetes (p &lt; 0.05). The activity of SOD and CAT as well as GSH content were increased by 2.7 times, 51.9 %, and 23.0 % (p &lt; 0.05), respectively. AST and ALT activities were 42.2 % and 74.3 % (p &lt; 0.05) reduced, respectively. The combined use of MIGU-4 (25.0 mg/kg) and vitamin E (250.0 mg/kg) caused a decrease in the brain MDA content by 70.1 % (p &lt; 0.05) in experimental rats. The combination of MIGU-4 and vitamin E increased the activity of GPO by 58.3 % (p &lt; 0.05) as compared to rats with diabetes, indicating cumulative effects of these drugs. Conclusions. The use of MIGU-4 prevents the occurrence of oxidant stress manifestations in the brain tissue and liver mitochondria in streptozotocin-induced diabetes. The corrective effect size of MIGU-4 (25.0 mg/kg) corresponds to that of vitamin E (250.0 mg/kg).

Effects of fluoride on oxidative DNA damage, nitric oxide level, lipid peroxidation and cholinesterase enzyme activity in a rotenone-induced experimental Parkinson’s model

ABSTRACT Objective Environmental toxins are known to be one of the important factors in the development of Parkinson’s disease (PD). This study was designed to investigate the possible contribution of fluoride (F) exposure to oxidative stress and neurodegeneration in rats with PD induced by rotenone (ROT). Materials and methods A total of 72 Wistar albino male rats were used in the experiment and 9 groups were formed with 8 animals in each group. ROT (2 mg/kg) was administered subcutaneously (sc) for 28 days. Different doses of sodium fluoride (NaF) (25, 50 and 100 ug/mL) were given orally (po) for 4 weeks. Malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO), oxidative DNA damage (8-OHdG) and cholinesterase (AChE/BChE) enzyme activities were evaluated in serum and brain tissue homogenates. Results Rats treated with ROT and NaF had significant increases in serum and brain MDA, NO content, and decreases in GSH. In addition, the combination of ROT and NaF triggered oxidative DNA damage and resulted in increased AChE/BChE activity. Conclusions Findings suggest that NaF and ROT may interact synergistically leading to oxidative damage and neuronal cell loss. As a result, we believe that exposure to pesticides in combination with NaF is one of the environmental factors that should not be ignored in the etiology of neurological diseases such as PD in populations in areas with endemic fluorosis.

Behavioral, Biochemical and Histopathological Evaluation of Sinapic acid for Antidepressant activity in Normal Mice and Stressed Mice

In this study, sinapic acid was evaluated for its effect on depressive behavior of normal mice and stressed mice. Swiss albino male mice were given unpredictable mild stressors for twenty-one consecutive days to produce depressive behavior. Sinapic acid (5, 10, 20 mg/kg) and fluoxetine (20 mg/kg) were given orally to mice for twenty-one days in succession. Depressive behavior was detected by tail suspension test and sucrose preference test. After behavioral testing, biochemical estimations were performed in plasma (nitrite, corticosterone) and brain (MAO-A, malondialdehyde, reduced glutathione, catalase, TNF-α). Histopathological studies on the brain were also performed. The immobility time of mice in the tail suspension test was remarkably decreased by sinapic acid (5 and 10 mg/kg). Sinapic acid restored the decreased sucrose preference in mice exposed to the stress paradigm. It also remarkably lowered concentration of plasma nitrite and corticosterone; brain malondialdehyde, monoamine oxidase- A and TNF-α; and increased the concentration of brain catalase and GSH in normal mice and also stressed mice. Histopathological studies indicated protective effect of sinapic acid against hyperchromatic nuclei in the brain. Thus, sinapic acid produced remarkable antidepressant effect in normal mice and also stressed mice. The possible mechanisms for the observed antidepressant effect of sinapic acid might be through inhibition of brain MAO-A, amelioration of neuroinflammation and oxidative stress; decrease of plasma corticosterone and protection against hyperchromatic nuclei in the brain.

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.

Single and Combined Effects of Chlorpyrifos and Glyphosate on the Brain of Common Carp: Based on Biochemical and Molecular Perspective.

Chlorpyrifos (CPF) and glyphosate (GLY) are the most widely used organophosphate insecticide and herbicide worldwide, respectively; co-occurrence of CPF and GLY in aquatic environments occurs where they inevitably have potential hazards to fish. However, the potential mechanisms of CPF and GLY to induce toxicity have not been fully explored. To identify the adverse impacts of CPF and GLY on fish, either alone or in combination (MIX), CPF (25 μg/L) and GLY (3.5 mg/L) were set up according to an environmentally relevant concentration to expose to common carp for 21 days. After exposure, CPF and GLY decreased the activities of acetylcholinesterase and Na+/K+-ATPase, altered monoamine oxidase levels, decreased antioxidant enzyme activities (superoxide dismutase, catalase, glutathione S-transferase and glutamic reductase), and induced the accumulation of malondialdehyde in the carp brain. The parameters in the MIX groups had a greater impact compared to that in the CPF or GLY group, suggesting that both single and combined exposure could affect neurological signaling systems and cause oxidative stress and lipid peroxidation damage in carp brains, and that MIX exposure increases the impact of each pollutant. RNA-seq results showed that single or combined exposure to CPF and GLY induced global transcriptomic changes in fish brains, and the number of differentially expressed genes in MIX-treated carp brains were globally increased compared to either the CPF or GLY groups, suggesting that the effects of co-exposure were greater than single exposure. Further analysis results revealed that the global transcriptomic changes participated in oxidative stress, immune dysfunction, and apoptosis of fish brains, and identified that the P13k-Akt signaling pathway participates in both single and combined exposure of CPF- and GLY-induced toxicity. Taken together, our results demonstrated that the interaction of CPF and GLY might be synergic and provided novel insights into the molecular mechanisms of fish brains coping with CPF and GLY.