Brain Superoxide Dismutase Research Articles

Effects of dendrobium polysaccharides on human brain microvascular endothelial cell injury induced by ox-LDL via regulating the miR-378 expression

Brain microvascular endothelial cells are a key part of the blood-brain barrier. This experiment was set up to investigate the effect and molecular mechanism of Dendrobium polysaccharide on oxidized low-density lipoprotein (ox-LDL)-induced damage to the human brain microvascular endothelial cells. For this purpose, human brain microvascular endothelial cells HBMEC were divided into control group (without any treatment), ox-LDL group (50 μg/mL ox-LDL), Dendrobium polysaccharide low, medium and high concentration group (0.1 μg/L, 0.2 μg/L, 0.4 μg/L Dendrobium polysaccharide+50 μg/mL ox-LDL), ox-LDL+miR-NC group (transfection miR-378 mimic negative control+50 μg/mL ox-LDL), ox-LDL+miR-378 group (transfected miR-378 mimics+50 μg/mL ox-LDL), ox-LDL+DP+anti-miR-NC group (transfected miR-378 inhibitor negative control +0.4 μg/L Dendrobium polysaccharide+50 μg/mL ox-LDL), ox-LDL+DP+anti-miR-378 group (transfected miR-378 inhibitor+0.4 μg/L Dendrobium polysaccharide+50 μg/mL ox-LDL ). The kit was used to detect the levels of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and catalase (CAT); flow cytometry to detect apoptosis; and Western blot to detect B-cell lymph tumor/leukemia-2 (Bcl-2) and Bcl-2 related X (Bax) protein expression; real-time fluorescence quantitative PCR (RT-qPCR) was used to detect the expression of miR-378. Results showed that after treatment with different concentrations of Dendrobium polysaccharides, MDA levels were decreased in ox-LDL-induced human brain microvascular endothelial cells, SOD and CAT activities were increased, apoptosis rate was decreased, Bcl-2 expression was increased, Bax expression was decreased, miR-378 expression was increased, in a dose-dependent manner (P<0.05). Overexpression of miR-378 inhibits ox-LDL-induced oxidative stress and apoptosis in human brain microvascular endothelial cells. Inhibition of miR-378 expression reversed the effect of Dendrobium polysaccharide on ox-LDL-induced damage to human brain microvascular endothelial cells. Then dendrobium polysaccharide may inhibit ox-LDL-induced oxidative stress and apoptosis in human brain microvascular endothelial cells by up-regulating the expression of miR-378.

Investigation of serum and brain superoxide dismutase levels depending on atomoxetine used in attention-deficit/hyperactivity disorder treatment: A combination of in vivo and molecular docking studies

This study aims to determine whether atomoxetine (ATX), used as an alternative to methylphenidate, affects superoxide dismutase (SOD) activity besides glutathione (GSH) and malondialdehyde (MDA) levels, apart from determining possible effects of ATX on SOD activity through molecular docking studies. 24 male Wistar rats were divided into 4 groups, each containing 6 members. After a 6-week application of ATX, blood samples and brain tissues were obtained from the rats for biochemical analyses. Besides, molecular docking studies were conducted using PyRx and Discovery Studio 3.0 programs. No significant difference occurred in GSH and MDA levels after ATX application. A high-dose application of ATX caused a statistically significant change only in the serum-SOD activity compared to that of Control Group. Molecular docking studies revealed that ATX settled in the biggest space rather than the catalytic regions of Cu2Zn2-SOD. Our biochemical and molecular docking data showed that ATX, an alternative drug to stimulant methylphenidate, showed no significant changes in the antioxidant defence system at either low or therapeutic doses after long-term use. Therefore, we suggest ATX could be used as a substitute for methylphenidate in the long-term treatment of ADHD.

Rutin ameliorates copper sulfate-induced brain damage via antioxidative and anti-inflammatory activities in rats.

Excessive exposure to Copper (Cu) may result in Cu toxicity and adversely affect health outcomes. We investigated the protective role of rutin on Cu-induced brain damage. Experimental rats were treated as follows: group I: control; group II: Cu-sulfate: 200 mg/kg; group III: Cu-sulfate, and rutin 100 mg/kg; and group IV: rutin 100 mg/kg, for 7 weeks. Cu only treatment significantly decreased body weight gain, while rutin cotreatment reversed this decrease. Cu treatment increased malondialdehyde, nitric oxide level, and myeloperoxidase activity and decreased superoxide dismutase and catalase activities in rat brain. Immunohistochemistry showed that COX-2, iNOS, and Bcl-2 proteins were strongly expressed, while Bax was mildly expressed in the brain of Cu-treated rats. Furthermore, brain histology revealed degenerated neurons, and perforated laminae of cerebral cortex in the Cu-only treated rats. Interestingly, coadministration of Cu and rutin reduced the observed histological alteration, improved inflammatory and antioxidant biomarkers, thereby protecting against Cu-induced brain damage via antioxidative and anti-inflammatory mechanisms.

Behavioral effects of zinc oxide nanoparticles on the brain of rats

Recent studies showed that zinc oxide nanoparticles (ZnO-NPs) can cause toxic damage to the central nervous system (CNS) after intraperitoneal injection; however, the behavioral effects of ZnO-NPs have not been fully investigated. This study aimed to resolve these discrepancies by examining the effects of poly(ethylene glycol)-based on the ZnO-NPs on antioxidant status in healthy rats. The structural, morphology and size characterization of nanoparticles were studied by applying techniques like XRD and TEM. Intraperitoneal injection of ZnO-NPs at a concentration of 25 mg/kg /day had no significant effect on the brain catalase (CAT), superoxide dismutase (SOD), and reduced glutathione content (GSH). Treatment with the 100 mg/kg dose of ZnO nanoparticles significantly increased brain MDA (P < 0.01), and significantly decreased brain catalase activity (P < 0.05), and brain superoxide dismutase activity (P < 0.05) compared to the control group. The high doses of ZnO-NPs caused prominent changes to brain histology. The results suggest that ZnO-NPs could induce behavioral changes and brain histological changes.

Neuroserpin extends the time window of tPA thrombolysis in a rat model of middle cerebral artery occlusion.

Tissue-type plasminogen activator (tPA) is characterized as an effective drug for early thrombolytic therapy in acute cerebral infarction (ACI). However, tPA will increase the risk of hemorrhage if it is used beyond the treatment time window. The study aims to explore the effects of neuroserpin (NSP) on the time window of tPA thrombolysis in ACI and the underlying mechanism. The middle cerebral artery occlusion (MCAO) model was constructed in rats, which were randomly divided into six groups: sham operation group, infarction group, 1-hour thrombolysis group, 1-hour thrombolytic + NSP intervention group, 4-hour thrombolytic group, and 4-hour thrombolysis + NSP intervention group. The neurological changes in rats were evaluated by modified neurological severity scores and rota-rod test. The brain edema and cerebral infarction area were evaluated by dry-wet method and triphenyl tetrazolium chloride staining. The blood-brain barrier (BBB) integrity was examined by Evans blue method. The expressions of malondialdehyde, superoxide dismutase, and glutathione peroxidase in brain were also investigated. The expression of caspase-3 and Bcl-2 in brain tissue and apoptosis of neurons were examined by Western blot analysis and toluidine blue staining. tPA thrombolysis significantly attenuated the neurological impairment in rats with MCAO at 1 hour. Conversely, the effect of tPA thrombolysis at 4 hours after MCAO did not significantly help the recovery of neurological function. However, a combination of tPA treatment and NSP treatment at 4 hours after MCAO markedly ameliorated the neurological impairment, cerebral edema, cerebral infarction volume, BBB injury, oxidative stress products, and neuron apoptosis. NSP can probably expand the time window for tPA treatment to reduce neurological impairment in ACI.

Ovarian Index of KM Mice Influenced by Longer Term Consumption of Microwave-Heated Milk

Microwave technology has been widely used in the food industry, but the effect of microwave-heated food on human health is being questioned. Female KM mice were chosen to be treated with microwave-heated milk (MM), and reproductive markers such as litter size, birth rate, survival rate, and ovarian index were evaluated. With longer term feeding, the reproductive status (body weight, birth rate, litter size, neonatal survival rate, interpregnancy interval, and brain superoxide dismutase and catalase activity) of KM mice treated with MM did not significantly change except for the ovarian index of first-generation mice, which was decreased significantly compared with the control group and the group given electrically heated milk. Longer term consumption of MM can affect the ovarian index of reproductive mice.

Effects of Long-Term Supplementation with Aluminum or Selenium on the Activities of Antioxidant Enzymes in Mouse Brain and Liver

The aim of this study was to investigate the effects of aluminum (Al) or selenium (Se) on the “primary” antioxidant defense system enzymes (superoxide dismutase, catalase, and glutathione reductase) in cells of mouse brain and liver after long-term (8-week) exposure to drinking water supplemented with AlCl3 (50 mg or 100 mg Al/L in drinking water) or Na2SeO3 (0.2 mg or 0.4 mg Se/L in drinking water). Results have shown that a high dose of Se increased the activities of superoxide dismutase and catalase in mouse brain and liver. Exposure to a low dose of Se resulted in an increase in catalase activity in mouse brain, but did not show any statistically significant changes in superoxide dismutase activity in both organs. Meanwhile, the administration of both doses of Al caused no changes in activities of these enzymes in mouse brain and liver. The greatest sensitivity to the effect of Al or Se was exhibited by glutathione reductase. Exposure to both doses of Al or Se resulted in statistically significant increase in glutathione reductase activity in both brain and liver. It was concluded that 8-week exposure to Se caused a statistically significant increase in superoxide dismutase, catalase and glutathione reductase activities in mouse brain and/or liver, however, these changes were dependent on the used dose. The exposure to both Al doses caused a statistically significant increase only in glutathione reductase activity of both organs.

The radio-protective effect of rosmarinic acid against mobile phone and Wi-Fi radiation-induced oxidative stress in the brains of rats.

Rosmarinus officinalis L. is an aromatic perennial herb from which rosmarinic acid (RA) can be extracted. This research was conducted to assess the effectiveness of RA against radio frequency (RF) radiation-induced oxidative stress due to 915MHz (mobile phone) and 2450MHz (Wi-Fi) frequencies in rats. The animals were separated into six groups, including group 1 receiving normal saline (NS), group 2 (NS/Wi-Fi) and group 4 (NS/mobile), which received NS plus 60min/day of exposure to the electromagnetic radiation (EMR) for 1month, group 3 (RA/Wi-Fi) and group 5 (RA/mobile) received RA (20mg/kg/day, po) plus 60min/day of EMR, and group 6 (RA) received only RA. There was a significant elevation of protein carbonylation (PC), nitric oxide (NO) and malondialdehyde (MDA) and significant reduction in glutathione (GSH), glutathione peroxidase (GPx), total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase (CAT) in the RF radiation-exposed rats' brain compared to the control group. RA reduced the levels of NO, PC and MDA and it also elevated the TAC, GPx, SOD, CAT and GSH levels in the rats' brains in the RA/Wi-Fi and RA/mobile groups compared to the NS/Wi-Fi and NS/mobile groups, respectively. It can be concluded that RA can be considered a useful candidate for protecting brain tissues against RF radiation-induced oxidative stress at 915 and 2450MHz frequencies through ameliorative effects on the antioxidant enzyme activities and oxidative stress indices.

β-Glucan Improves Conditions of Chronic Fatigue in Mice by Stimulation of Immunity

Background: Various natural molecules have been studied for the enhancement of physical endurance. Glucan has been found to improve various stress-related conditions and to improve fatigue and endurance. Objective: In our study, we focused on evaluation of glucan effects on some reactions involved in chronic fatigue. Methods: We measured phagocytosis of neutrophils, the production of IL-2, IL-4, and IL-10 by spleen cells, and levels of antioxidant glutathione and oxidative stress marker superoxide dismutase in brain. In addition, we measured the effects of glucan on water immersion and on rotarod. Results: The glucan supplementation strongly improved the suppressed phagocytosis and changes in cytokine and levels of oxidative stress markers caused by fatigue. In addition, glucan supplementation also increased the motor functioning of tested animals. Conclusion: Our data suggested that anti-fatigue properties of glucan are related with its well-established effects as stimulator of immune reactions.

Investigations on the anti-aging activity of polysaccharides from Chinese yam and their regulation on klotho gene expression in mice

In this study, Chinese yam polysaccharides (CYP) were extracted from the tuber of Dioscorea opposita Thunb. by hot-water extraction and ethanol precipitation. After deproteinized by the Sevag method, the content of CYP was determined to be 91.77%. The anti-aging activities of the CYP were evaluated in aging mice induced by d-galactose in vitro and in vivo. The results indicated that the CYP not only could enhance the learning ability of mice, but alleviate the spatial memory impairment of mice. Furthermore, the CYP could effectively inhibit the formation of malondialdehyde and enhance the activities of superoxide dismutase, catalase and glutathione peroxidase in brain, liver and kidney tissues of mice. The histological analysis indicated that CYP could significantly alleviate the damages induced by d-galactose in the above tissues. Gene expression studies showed that the CYP could up-regulate the expression of anti-aging klotho gene in brain and kidney. Therefore, it can be concluded that the anti-aging effect of Chinese yam may be achieved by repairing the function of organs and improving the expression of klotho gene in mice.

Mesenchymal stem cells’ therapeutic potential for endotoxin-induced brain and spleen injuries in rats

Background and objective Inhalation of bacterial endotoxin induces an acute inflammation in various organs, especially the brain and spleen. This study examined the therapeutic effects of bone marrow mesenchymal stem cells (BM-MSCs) in lipopolysaccharide (LPS)-induced brain-spleen injuries in rats as compared with dexamethasone. Materials and methods A total of 32 male Wistar albino rats, weighing 180–200 g, were used in the study and were divided into four groups. Group 1 (normal) rats received 20 μl of saline in each nostril for two consecutive days. Group 2 animals received LPS (20 μl of LPS of Escherichia coli in each nostril for 2 consecutive days) that induced brain-spleen injuries and served as a positive control group. Group 3 animals were injected with dexamethasone (2 mg/kg, once, intraperitoneal). Group 4 animals received (1×106) BM-MSCs in 500 μl PBS/rat via intraperitoneal injection once before acute injury induction with LPS. At the end of the experiment, the authors studied the sickness behavior by assessing open field behavior and measured oxidative and inflammatory parameters. Results and conclusion LPS-induced open field behavior impairments (decreased locomotion and rearing and increased immobility), with elevation of a number of inflammatory cells, especially neutrophils. Moreover, LPS-induced elevation of lipid peroxidation along with reduction of both reduced glutathione and superoxide dismutase in brain and spleen tissues and increased interleukin-1β and myeloperoxidase contents in rats, compared with normal group. These harmful effects were hindered after treatment with MSCs. In conclusion, MSCs prevented both sickness and depressive-like behavior via neuroinflammatory pathway and could be a novel approach to therapy for LPS-induced serious injuries in rats but needs further clinical studies.

Differential effect of Ca2+ on mitochondrial superoxide dismutase and catalase activities in the aging brain

Mitochondrial participation in cellular free radical generation constitutes more than 80% of the total. Free radicals tend to be harmful and cause oxidation of proteins and lipids in the cell and hence they are proposed as an important factor affecting aging. However, the antioxidant capacity to catapult oxidative stress in mitochondria is imminent to delay aging. More so, mitochondrial Ca2+ sequestration has some profound effect on ROS production and detoxification. In the current study, we have investigated the effect of Ca2+ on age-related alterations in antioxidant enzymes like sodium dismutase and catalase activities. The spectro-photometric measurement of both sodium dismutase and catalase has shown a differential response to Ca2+. Sodium dismutase has shown a downward trend in activity for varying concentrations of Ca2+ treatment in aging while catalase has not shown much deviation in its activity levels, except for a small rise in aged animals. Thus, Ca2+ seems to be differentially affecting the activity of two antioxidant enzymes in the mitochondrial isolate.

Protective Effects of Adrenomedullin on Rat Cerebral Tissue After Transient Bilateral Common Carotid Artery Occlusion and Reperfusion.

ObjectiveWe aimed to investigate the protective effect of adrenomedullin (ADM) on cerebral tissue of rats with cerebral ischemia/reperfusion (I/R) injury.MethodsThirty-two Wistar rats were randomized into four groups (n=8). In the I/R Group, bilateral common carotid arteries were clamped for 30 minutes and, subsequently, reperfused for 120 minutes. In the ADM Group, rats received 12 µg/kg of ADM. In the I/R+ADM Group, bilateral common carotid arteries were clamped for 30 minutes and, subsequently, the rats received 12 µg/ kg of ADM. Then, reperfusion was performed for 120 minutes. The Control Group underwent no procedure. Blood and brain tissue samples were collected for biochemical and histopathological analysis. Serum malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were analysed. Brain tissue was evaluated histopathologically and neuronal cells were counted in five different fields, at a magnification of ×400.ResultsBrain MDA in I/R Group was significantly higher than in ADM Group. Brain GPx and SOD in I/R+ADM Group were significantly higher than in I/R Group. The number of neurons was decreased in I/R Group compared to the Control Group. The number of neurons in I/R+ADM Group was significantly higher than in I/R Group, and lower than in Control Group. Apoptotic changes decreased significantly in I/R+ADM Group and the cell structure was similar in morphology compared to the Control Group.ConclusionWe demonstrated the cerebral protective effect of ADM in the rat model of cerebral I/R injury after bilateral carotid artery occlusion.

Injury factors and pathological features of toxic milk mice during different disease stages.

ObjectiveTo evaluate different injury factors and pathological characteristics of the brain at different disease stages in toxic milk (TX) mice, an animal model of Wilson's disease (WD).MethodsThirty TX mice (10 each at 3, 6 and 12 months old) and 30 age‐matched C57 mice were used in this study. Corrected phase (CP) values were determined from susceptibility‐weighted images. Myelin content was determined by measuring inhibition optical density values of Luxol fast blue‐stained sections. Neurofilament protein 68 kDa (NF68), β‐amyloid precursor protein (β‐APP), and myelin basic protein (MBP) levels, as well as copper and iron content, in brain nuclei of the TX mouse were evaluated. Gene amplification ratios for catalase (CAT), GSH peroxidase (GSH‐PX), nitric oxide synthase (NOS), and superoxide dismutase (SOD) in mouse brain were also determined.ResultsCompared with C57 mice, neuronal cell counts were decreased in 12‐months‐old TX mice (p = .011). Myelin content was decreased in the lenticular nucleus (p = .029), thalamus (p = .030), and brainstem (p = .034) of 6‐months‐old TX mice; decreases in the corresponding nuclei (p = .044, .037, and .032, respectively) were also found in 12‐months‐old TX mice. MBP values were lower in the lenticular nucleus and thalamus (p = .027 and .016, respectively) of 6‐months‐old TX mice and in the corresponding nuclei (p = .24 and .040) of 12‐months‐old TX mice. NF‐68 values were lower in the lenticular nucleus and thalamus (p = .034 and .037, respectively) of 6‐months‐old TX mice and in the corresponding nuclei (p = .006 and .012) of 12‐months‐old TX mice. β‐APP values were higher in the thalamus of 6‐months‐old (p = .037) and 12‐months‐old (p = .012) TX mice. Iron content was higher in the lenticular nucleus, thalamus, and cerebellum (p = .044, .038, and .029, respectively) of 6‐months‐old TX mice and in the corresponding nuclei (p = .017, .024, and .029) of 12‐months‐old TX mice. The NOS gene amplification multiple was higher (p = .039), whereas the SOD1 gene amplification multiple was lower (p = .041) in 12‐months‐old TX mice. There was no correlation between metal content or oxidation index and pathological index.ConclusionsThe pathological characteristics of the brains of TX mice may differ at different ages. Different pathogenic factors, including copper and iron deposition and abnormal oxidative stress, are present at different stages.

Protective Efficacy of Vitamin F against Acrylamide Induced Toxicity: Studies on Oxidative Stress Biomarkers

Introduction:Vitamin F is also known as Linoleic Acid (LA), is an Essential Fatty Acid (EFA) which is not produced in humans. It can be modified to form essential precursors such as arachidonic acid which is used to make prostaglandins, thromboxanes, and leukotrienes. It is found in abundance in several vegetable oils such as sunflower, poppy seed, safflower and corn oils. LA has shown diverse beneficial effects against diseases such as cancer, skin permeability, insulin resistance, depression and cardiovascular diseases. Acrylamide (AA) is a well known neurotoxic, carcinogenic and genotoxic compound. It is used universally in the industrial process and recently found in various food products which are cooked at a temperature above 120˚C such as potato crisps, bread, cookies and french fries. Over exposure of humans and laboratory animals to monomer AA causes damages to the central and peripheral nervous system.Objective:To investigate the therapeutic effect of linoleic acid against acrylamide toxicity.Methods:AA was given at 38.27 mg/kg dose for 10 days and therapy with different doses of linoleic acid for three days (11-13 days) to female albino rats.Results:Signs and symptoms of acrylamide toxicity occur, they include significant body weight reduction, hair loss, splaying of hindlimbs, dragging of back legs and skin irritation. A significant decline was observed in hemoglobin level and GSH, whereas significant enhancement in LPO was noted, as compared to the control group after AA exposure. The activity of acetylcholinesterase was decreased in the brain after AA administration. AA significantly reduced the superoxide dismutase and catalase activities in liver, kidney and brain but activities of serum transaminases, bilirubin, creatinine, urea and lipid profile increased in serum. Biochemical studies were also strengthened by histopathological observations.Conclusion:Study has shown that linoleic acid promotes defense against AA toxicity.

Propiconazole induces abnormal behavior and oxidative stress in zebrafish.

The use of pesticides has been growing along with the demand for agricultural products. These compounds, however, are not restricted to the field, spreading easily through the soil, contaminating groundwater and reaching urban centers. Propiconazole is a triazole fungicide that has been increasingly used in agriculture. However, there are few data about its effects on non-target organisms. This study aimed to evaluate the effects of propiconazole in zebrafish. The animals were exposed for 96 h to different concentrations of propiconazole (425, 850, 1700, 8500 ng/L), then submitted to the novel tank test for behavioral analyses. The brains were collected for evaluation of oxidative stress parameters. Exposure to propiconazole (1700 and 8500 ng/L) decreased the number of crossings, entries, and time spent in the top, and increased the time spent in the bottom area of the tank. We also observed an increase in the activities of superoxide dismutase and catalase in zebrafish brain exposed to propiconazole at 425, 850, and 1700 ng/L. We conclude that propiconazole alters normal fish behavior and disrupts oxidative status. More studies are necessary to elucidate the exact mechanism underlying the effects of propiconazole on non-target-organisms.

A Synthetic Pro-Drug Peptide Reverses Amyloid-β-Induced Toxicity in the Rat Model of Alzheimer's Disease.

Alzheimer's disease (AD), the most prevalent neurodegenerative disorder, involves the formation of the extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles. The current therapies against AD are symptomatic with limited benefits but associated with major side effects. Inhibition of self-aggregation of Aβ peptides into higher order cross-β structure is one of the potential therapeutic approach which may counter oligomerization of Aβ peptide. The present study aimed to evaluate the neuroprotective and anti-inflammatory potential of a synthetic Pro-Drug type peptide (PDp) against Aβ-induced toxicity in rat model of AD. Intra-hippocampal microinjection of toxic Aβ40 (IHAβ40) by stereotaxic surgery was performed in the male Sprague-Dawley rats to generate an Aβ-induced AD model. Sub-chronic toxicity of synthetic PDp using hematological, biochemical, and histopathological parameters was investigated. Evaluation of PDp on Aβ-induced neurodegeneration and neuroinflammation was performed. PDp inhibits plaque formation with increase in Nissl granule staining in the rat hippocampus. Aβ-induced toxicity associated imbalance in reactive oxygen species and antioxidant enzymes activity such as superoxide dismutase and catalase in the rat brain was overcome by PDp treatment. Tau protein hyperphosphorylation was normalized with PDp treatment. Also, the neuroinflammatory response was suppressed with PDp treatment. The present study depicts the potential neuroprotective role of PDp against Aβ-induced toxicity in rat. PDp inhibits plaque formation thereby normalizing oxidative stress, inhibiting tau protein hyperphosphorylation, and suppressing neuroinflammatory responses. Future studies done in this direction will pave way for new therapeutic strategies.

Antihypernociceptive and neuroprotective effects of Combretin A and Combretin B on streptozotocin-induced diabetic neuropathy in mice.

Painful diabetic neuropathy (PDN) is known to adversely affect psychosocial functioning by enhancing levels of anxiety and depression. This study was designed to verify the antihypernociceptive, anxiolytic, and antidepressant-like effects of Combretin A and Combretin B (two triterpenes cycloartane-type isolated from the leaves of Combretum fragrans) in streptozotocin-induced diabetic neuropathy in mice. PDN was induced in mice by the administration of streptozotocin (STZ, 200mg/kg, i.p.). The effect of oral administration of Combretin A (25 and 50mg/kg) and Combretin B (25 and 50mg/kg) on nociception (mechanical allodynia, thermal hyperalgesia, cold allodynia, and chemical hyperalgesia), anxiety (elevated plus maze, light-dark box test, social interaction), and depressant (open field test, forced swimming test, tail suspension test) was evaluated. Combretin A (25 and 50mg/kg) and Combretin B (25 and 50mg/kg) caused antihypernociceptive, anxiolytic, and antidepressant-like effects in in STZ-induced diabetic neuropathy in mice. Both compounds also caused a decrease in blood glucose and improved body weight in treated animals. They also significantly (p < 0.001) reduced tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), malondialdehyde (MDA), and nitric oxide (NO) production in serum and sciatic nerves, and, significantly (p < 0.001) increased superoxide dismutase (SOD) and catalase (CAT) activity in serum, sciatic nerves, and brain. Combretin A and Combretin B also showed a great systemic effect, conserving values of evaluated parameters close to normal in treated mice. The results of this study confirm the antihypernociceptive, antianxiety, and antidepressant activities of Combretin A and Combretin B.

Effects of Moxibustion on Central Fatigue in Rats Subjected to Different Degrees of Exhaustive Exercise

Abstract Objective To observe the effects of moxibustion on central fatigue in rats subjected to different degrees of exhaustive exercise. Methods The exhaustive exercise model was established through repeated trials of swimming. Ninety-six male SD rats were randomly divided into the following three groups: a control group (n=32) that did not undergo the exercise routine, an untreated group (n=32) that received no treatment after exercise, and a moxibustion group (n=32) that received a mild dose of moxibustion at “Shénquè” (CV 8) for 15 min after exercise. Rats in each group were randomly and equally divided into 1st, 4th, 7th and 10th trial subgroups according to exercise duration. The levels of hippocampal tissue monoamine neurotransmitters 5-hydroxytryptamine (5-HT), Dopamine(DA) and free radicals Malondialdehyde (MDA), Superoxide dismutase (SOD), Glutathione peroxidase (GSH-Px) were measured after the exhaustive exercise protocol for each group. Results The exhaustive duration of rats in the 4th trial untreated subgroup was significantly longer than the 1st trial untreated subgroup, while the 7th and 10th trial untreated subgroups were significantly shorter than the 1st trial untreated subgroup. The 7th and 10th trial moxibustion subgroups were longer than the corresponding untreated subgroups. Compared with the control group, the levels of 5-HT and MDA in rat brains for each untreated subgroup were higher and the GSH-Px levels in the 4th, 7th and 10th trial untreated subgroups were lower. The levels of brain DA and SOD in rats from the 1st trial untreated subgroup were significantly higher than controls and then decreased. The 7th and 10th trial untreated subgroups were significantly lower. Compared with the corresponding untreated subgroups, the levels of rat brain 5-HT in the 7th and 10th trial moxibustion subgroups were decreased, the MDA levels in the 4th, 7th and 10th trial moxibustion subgroups were decreased, and the DA,SOD, GSH-Px levels in the 4th, 7th and 10th trial moxibustion subgroups were increased. Conclusions Moxibustion relieved exercise-induced central fatigue in long-term exercise by reducing the levels of 5-HT and MDA while increasing the levels of DA, SOD, and GSH-Px, effectively extending the duration of the exhaustive exercise.

Impact of chronic low dose exposure of monocrotophos in rat brain: Oxidative/ nitrosative stress, neuronal changes and cholinesterase activity.

Monocrotophos (MCP) is an organophosphate mainly used as insecticides in agriculture, and veterinary practice to control pests. Exposure to MCP is known to induce significant systemic toxicity in animals and humans. Short term exposure to a high dose of MCP has been reported to cause systemic toxicity, however limited information is available regarding low dose long term exposure in rats. We studied the effects of low dose long term exposure to MCP on oxidative/nitrosative stress, cholinesterase activity and neuronal loss in rat. Male rats were exposed to MCP (0.1 μg or 1 μg/ml) via drinking water for 8 weeks. The pro-oxidant markers such as reactive oxygen species (ROS), lipid peroxidation (MDA), nitrite level and antioxidant markers such as reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and inhibition of cholinesterase activities were measured to evaluate the effects of MCP on brain along with plasma cholinesterase activity. Neuronal loss was analyzed in cortical region using H&E stained slices. The results suggested that exposure to MC even at the low dose, increased reactive oxygen species, thiobarbituric acid reactive substance levels and decreased glutathione, superoxide dismutase, catalase and cholinesterase activities in brain. No significant effect however, was observed on nitrite levels. Histological analysis revealed that low dose MCP exposure lead to structural changes in the cortical neurons in rats. It can be concluded from the study that low dose long term exposure (lower than No Observed Effect Level) of MCP may lead to the generation of oxidative stress by elevation of pro-oxidants markers and depletion of antioxidant enzymes markers along with inhibition of cholinesterase activity. These changes might thus be considered as the possible mechanism of cortical neuronal loss in these animals.