Brain Glutathione Research Articles

In vivo monitoring of glutathione in a live rat brain based on the ratiometric signal output of 2D Cu-TCPP(Fe) nanosheets.

Herein, a novel ratiometric electrochemical platform was developed for in vivo analysis of GSH based on the dual signal output of 2D Cu-TCPP(Fe) nanosheets. Our method with high selectivity and high accuracy enabled GSH monitoring in a live rat brain, and accurate GSH concentrations were firstly reported in different brain regions upon global cerebral ischemia.

Long-Term Sleep Deprivation-Induced Myocardial Remodeling and Mitochondrial Dysfunction in Mice Were Attenuated by Lipoic Acid and N-Acetylcysteine.

The impact of long-term sleep deprivation on the heart and its underlying mechanisms are poorly understood. The present study aimed to investigate the impact of chronic sleep deprivation (CSD) on the heart and mitochondrial function and explore an effective drug for treating CSD-induced heart dysfunction. We used a modified method to induce CSD in mice; lipoic acid (LA) and N-acetylcysteine (NAC) were used to treat CSD mice. Echocardiography, hematoxylin-eosin (H&E) staining, Sirius red staining, and immunohistochemistry were used to determine heart function and cardiac fibrosis. The serum levels of brain natriuretic peptide (BNP), superoxide Dismutase (SOD), micro malondialdehyde (MDA), and glutathione (GSH) were measured to determine cardiovascular and oxidative stress-related damage. Transmission electron microscopy was used to investigate mitochondrial damage. RNA-seq and Western blotting were used to explore related pathways. We found that the left ventricular ejection fraction (LVEF) and fraction shortening (LVFS) values were significantly decreased and myocardial hypertrophy was induced, accompanied by damaged mitochondria, elevated reactive oxygen species (ROS), and reduced SOD levels. RNA-sequence analysis of the heart tissue showed that various differentially expressed genes in the metabolic pathway were enriched. Sirtuin 1 (Sirt1) and Glutathione S-transferase A3 (Gsta3) may be responsible for CSD-induced heart and mitochondrial dysfunction. Pharmacological inhibition of ROS by treating CSD mice with LA and NAC effectively reduced heart damage and mitochondrial dysfunction by regulating Sirt1 and Gsta3 expression. Our data contribute to understanding the pathways of CSD-induced heart dysfunction, and pharmacological targeting to ROS may represent a strategy to prevent CSD-induced heart damage.

Involvement of TRPM7 Channel on the Induction of Diabetic Neuropathic Pain in Mice: Protective Role of Selenium and Curcumin.

Excessive levels of the mitochondrial reactive oxygen radical (mitSOX) and Ca2+ influx were found to cause neuropathic pain in patients with diabetes mellitus (DM). Naltriben (NLT) and mitSOX activate the transient receptor (TRP) melastatin 7 (TRPM7) channel, but antioxidants and carvacrol inhibit it. Selenium (Se) and curcumin (CRC) have been thoroughly studied for their modulator effects on streptozotocin (STZ)-induced neuropathic pain, apoptosis, and oxidative stress through the blockage of TRP channels in dorsal root ganglion (DRG) neurons. It has not yet been fully understood how Se and CRC protect against STZ-induced neuropathic pain by modulating TRPM7. Here, we assessed how Se and CRC affected the Ca2+ influx, mitSOX-mediated oxidative damage, and apoptosis in the DRGs of mice through modifying TRPM7 activity. Seven groups (control, Se, CRC, STZ, STZ + Se, STZ + CRC, and STZ + Se + CRC) were induced from the 56 male mice. We observed that the STZ-induced stimulation of TRPM7 increased mechanical neuropathic pain (von Frey), thermal neuropathic pain (hot plate), cytosolic Ca2+, TRPM7 current density, TRPM7 expression, lipid peroxidation, mitSOX, cytosolic ROS, apoptosis, caspase-3, caspase-8, and caspase-9 concentrations, whereas Se and CRC therapies diminished the alterations. The STZ-mediated decreases of DRG viability, brain glutathione, glutathione peroxidase, vitamin A, and vitamin E concentrations were also upregulated in the treatment groups by the therapies. These findings collectively imply that an imbalance of neuropathic pain, oxidative neurotoxicity, and apoptosis in the mice is caused by the STZ-mediated activation of TRPM7. However, the downregulation of TRPM7 activity caused by the injections of Se and CRC reduced the neurotoxicity and apoptosis.

Therapeutic Potential of Dragea volubilis Leaf Extract against Scopolamine-induced Memory Impairment in Young and Aged Mice

Background: Treating neurological disorders is still a major challenge, especially diseases like alzheimer's. Dragea volubilis is a wonder herb with many pharmacological activities like neuroprotective, antioxidant, anti-tumor, and anti-inflammatory. Dragea volubilis is synonymously known as Wattakaka volubilis. Chemical exploration of Dragea volubilis has yielded polyoxypregnane glycosides. Objectives: This study focused to explore the cognition-enhancing and neuroprotective functions of chloroform extract of Dragea volubilis in young and old mice in interoceptive and exteroceptive models. Materials and Methods: The chloroform extract of Dragea volubilis (CDV) was prepared by the soxhlation method. The antioxidant, anticholinesterase, and behavioral parameters were assessed through avoidance, elevated plus, and morris water maze. In-vivo studies were conducted by dividing the animals into 4 groups exteroceptive and 5 interoceptive (scopolamine-induced amnesia) 6 animals in each group. The scopolamine was administered at 2mg/kg and the extract of Dragea volubilis was administered at two different doses (100, and 200 mg/kg) for 14 days. Animals were sacrificed after behavioral parameters and brains were isolated for antioxidants and acetylcholinesterase assays. Results: A marked increase in step-down latency (SDL- passive avoidance) and a significant reduction in transfer latency (TL) in the elevated plus maze were noticed with the extract. It also demonstrated significant improvement in memory in the morris water maze (MWM) test in both the training and retention trials. CDV inhibited acetylcholinesterase and reduced thiobarbituric acid reactive substance activity (TBARS) and increased glutathione (GSH) and catalase in the mice brain showing significant antioxidant properties. Conclusion: It can be concluded with results that CDV has significant potential as a nootropic and antioxidant with neuroprotective properties.

Age-Related Oxidative Redox and Metabolic Changes Precede Intraneuronal Amyloid-β Accumulation and Plaque Deposition in a Transgenic Alzheimer's Disease Mouse Model.

Many identified mechanisms could be upstream of the prominent amyloid-β (Aβ) plaques in Alzheimer's disease (AD). To profile the progression of pathology in AD. We monitored metabolic signaling, redox stress, intraneuronal amyloid-β (iAβ) accumulation, and extracellular plaque deposition in the brains of 3xTg-AD mice across the lifespan. Intracellular accumulation of aggregated Aβ in the CA1 pyramidal cells at 9 months preceded extracellular plaques that first presented in the CA1 at 16 months of age. In biochemical assays, brain glutathione (GSH) declined with age in both 3xTg-AD and non-transgenic controls, but the decline was accelerated in 3xTg-AD brains from 2 to 4 months. The decline in GSH correlated exponentially with the rise in iAβ. Integrated metabolic signaling as the ratio of phospho-Akt (pAkt) to total Akt (tAkt) in the PI3kinase and mTOR pathway declined at 6, 9, and 12 months, before rising at 16 and 20 months. These pAkt/tAkt ratios correlated with both iAβ and GSH levels in a U-shaped relationship. Selective vulnerability of age-related AD-genotype-specific pAkt changes was greatest in the CA1 pyramidal cell layer. To demonstrate redox causation, iAβ accumulation was lowered in cultured middle-age adult 3xTg-AD neurons by treatment of the oxidized redox state in the neurons with exogenous cysteine. The order of pathologic progression in the 3xTg-AD mouse was loss of GSH (oxidative redox shift) followed by a pAkt/tAkt metabolic shift in CA1, iAβ accumulation in CA1, and extracellular Aβ deposition. Upstream targets may prove strategically more effective for therapy before irreversible changes.

Exploring the protective effect exhibited by curcumin-loaded coconut oil microemulsion in the experimental models of neurodegeneration: an insight of formulation development, in vitro and in vivo study

BackgroundNeurodegenerative diseases are a major health concern which requires promising drugs with appropriate drug delivery systems. The aim of the present study was development and characterization of curcumin-loaded coconut oil microemulsion (Cur-ME) and to improve the pharmacokinetic and pharmacodynamics performance. Initially, solubility study and emulsification study were performed for preliminary screening of the components. Pseudoternary phase diagram was constructed using selected components, and composition of Cur-ME was finalized. Furthermore, in vitro drug release in vivo pharmacokinetics and pharmacodynamic was performed.ResultsThe final formulation exhibited globule size less than 20 nm with PDI and zeta potential as 0.24 and −17 mV, respectively. The formulation showed more than 90% drug content with no signs of precipitation upon dilution and centrifugation. In vitro drug release revealed 2.12-fold improvement in dissolution. In vivo plasma pharmacokinetics of Cur-ME revealed twofolds and 2.48-fold improvement in AUC and Cmax, respectively, than that of Cur-Sol. In vivo pharmacokinetics in adult zebrafish revealed significant enhancement (p < 0.01) in curcumin delivery to the brain with 1.96-fold and 1.92-fold improvement in Cmax and AUC, respectively. Furthermore, the pharmacodynamics of the formulation was evaluated using trimethyl tin (TMT)-induced neurodegeneration in wistar rats. The results revealed that Cur-ME treated group significantly decreased the escape latency and pathlength as compared to the neurodegeneration control group. The observed effects were also markedly significant than Cur-Sol treated group. Further, the brain malondialdehyde (MDA) and glutathione (GSH) levels were found to be increased significantly as compared to Cur-Sol treated group.ConclusionThe encouraging results exhibited by Cur-ME can be regarded as a mark of an effective formulation that can be used in neurodegeneration. Overall, these findings indicate that an orally delivered microemulsion has enormous potential for drug delivery to the brain.

The impact of breed, Ficus exasperata leaf powder and vitamin C on carcass traits, brain and meat oxidative enzymes of broiler chickens raised under the tropical condition.

This study aims to see how supplementing broiler chickens with Ficus exasperata leaf powder (FELP) and vitamin C affects carcass characteristics, brain and meat oxidative enzymes and cholesterol levels in tropical conditions. Three hundred thirty-six-day-old chicks (comprising of 168 Cobb 500 breed chicks and 168 Arbor Acre breed chicks) of broiler chicks weighing 37.40 ± 0.45g were assigned to 8 experimental diets of 7 replicates (6 birds/replicate; 42 birds/treatment). Diets 1 and 2 were not supplemented, while diets 3 and 4 had vitamin C (200mg/kg of basal diet) supplementation. Then, diets 5 and 6 received 1g FELP/kg of basal diet supplementation each while diets 7 and 8 had 1g FELP/kg of basal diet + 200mg of vitamin C. The breed and FELP affected (P < 0.05) the dressing percentage. The relative weights of the gizzard and heart were affected (P < 0.05) by the vitamin c and FELP, while the lung weight was affected by vitamin C. The proventriculus was affected by the breed, FELP and vitamin c. The brain catalase and glutathione peroxidase increased with vitamin c and FELP supplementation while catalase and glutathione peroxidases were higher in CO. Vitamin c and FELP reduced the meat lipid oxidation but increased the glutathione peroxidase and catalase. Conclusively, dietary supplementation with 200mg/kg of vitamin C and 1% FELP could increase the brain's antioxidant capacity and improve the meat quality of broiler chickens.

Protein Carbonyl, Lipid Peroxidation, Glutathione and Enzymatic Antioxidant Status in Male Wistar Brain Sub-regions After Dietary Copper Deficiency.

Copper a quintessential transitional metal is required for development and function of normal brain and its deficiency has been associated with impairments in brain function. The present study investigates the effects of dietary copper deficiency on brain sub-regions of male Wistar rats for 2-, 4- and 6-week. Pre-pubertal rats were divided into four groups: negative control (NC), copper control (CC), pairfed (PF) and copper deficient (CD). In brain sub regions total protein concentration, glutathione concentration and Cu-Zn SOD activity were down regulated after 2-, 4- and 6weeks compared to controls and PF groups. Significant increase in brain sub regions was observed in protein carbonyl and lipid peroxidation concentration as well as total SOD, Mn SOD and catalase activities after 2-, 4- and 6weeks of dietary copper deficiency. Experimental evidences indicate that impaired copper homeostasis has the potential to generate reactive oxygen species enhancing the susceptibility to oxidative stress by inducing up- and down-regulation of non-enzymatic and enzymatic profile studied in brain sub regions causing loss of their normal function which can consequently lead to deterioration of cell structure and death if copper deficiency is prolonged.

Effects of chronic exposure of naturally weathered microplastics on oxidative stress level, behaviour, and mitochondrial function of adult zebrafish (Danio rerio)

Microplastics (MPs) are a big and growing environmental concern, with studies showing sublethal to acute biological impacts on typical aquatic organisms. However, little is known about the biological effects of naturally weathered MPs, particularly focusing on mitochondria dysfunction as the key trigger of the biological effects. Therefore, in this study, naturally weathered MPs were produced from day-to-day life products, characterized, and chronically exposed (21 days) to adult zebrafish at the concentration of 0.1 and 1 mg/L. Locomotion and unconditioned anxiety-like behaviour was assessed. Mitochondrial respiration, membrane potential, mitochondrial complex activity and oxidative-related parameters were evaluated in the brain and liver. The results revealed the weathered MPs as a copolymer of propylene and ethylene that induced anxiety-like behaviour. There was an increase in brain catalase activity while the brain lactate dehydrogenase activity was inhibited after exposure to 1 mg/L. Brain glutathione levels were increased while their ratio was not affected. Mitochondrial respiratory chain complex Ⅱ and IV were also significantly decreased in the brain, although not compromising mitochondrial function. On the other hand, exposure to 1 mg/L caused a deficiency in liver mitochondrial respiration and decreased mitochondrial membrane potential, which were associated with the mitochondrial respiratory chain inhibition. An increase in hepatic superoxide dismutase and catalase activity was noticed, supporting the occurrence of ROS-induced ROS release as the potential trigger for the mitochondrial dysfunction. Overall, these findings highlight the potential indirect and cumulative environmental effects these particles may pose to aquatic ecosystems.

Analgesic effects of Terminalia chebula extract are mediated by the suppression of the protein expression of nerve growth factor and nuclear factor-κB in the brain and oxidative markers following neuropathic pain in rats.

Due to the complications related to the use of the current pharmacological approach for the alleviation of neuropathic pain, searching for effective compound with fewer complications is a requirement of the present era. It is well known that the pathophysiological mechanism of neuropathic pain is related to excessive inflammation in the nervous system. Hence, the present study focuses on whether the potential analgesic effects of Terminalia chebula (TC) extract are mediated by the changes in the protein expression of nerve growth factor (NGF) and nuclear factor-kappa B (NF-κB) in the brain in a rat model of sciatic nerve chronic constriction injury (CCI). Neuropathic pain was induced by the left sciatic nerve CCI. Male Wistar rats were assigned to three groups: sham, CCI, and CCI + TC (40mg/kg). Animals received either normal saline (1 mL) or the aqueous-alcoholic extract of TC (40mg/kg) for 30 days via gavage needles once a day. Cold allodynia and anxiety-like behaviors were examined one day before CCI surgery (day - 1), as well as days 2, 7, 14, and 30 following CCI. We also assessed the effects of the TC extract oxidative stress markers on day 30 following CCI. Moreover, a western blot analysis was performed on day 30 following CCI to evaluate the effects of the TC extract on the protein expression of NGF and NF-κB in the brain. Oral gavage of the TC extract significantly decreased cold allodynia on days 2 and 14 following CCI. Additionally, the CCI model of chronic pain significantly increased the protein expression of NGF and NF-κB in the brain on day 30 following CCI. Furthermore, the TC extract significantly decreased the protein expression of NGF and NF-κB in the brain. The TC extract also significantly increased the brain glutathione (GSH) content and decreased the malondialdehyde (MDA) content. It is suggested that the analgesic effects of the TC extract are mediated by the suppression of brain NGF, NF-κB, and by its antioxidant activity in the brain following neuropathic pain in rats.

Prophylactic administration of rosmarinic acid ameliorates depression-associated cardiac abnormalities in Wistar rats: Evidence of serotonergic, oxidative, and inflammatory pathways.

Psychiatric disorders and associated cardiac comorbidities have increased the risk of mortality worldwide. Researchers reported that depression increases the possibility of future cardiac abnormalities by approximately 30%. Therefore, there is an unmet need to develop therapeutic interventions to treat depression and associated cardiac abnormalities. The present study was conducted to evaluate the prophylactic effect of rosmarinic acid (RA) against chronic unpredictable stress (CUS)-induced depression associated cardiac abnormalities in Wistar rats. The CUS paradigm, which comprised several stressors, was employed for 40 days to induce depressive-like behavior and associated cardiac abnormalities in rats. Along with CUS, RA at a dose of 25 and 50 mg/kg was administered orally to two groups of animals for 40 days. Behavioral tests (forced swim test and sucrose consumption test) and molecular biomarkers (corticosterone and serotonin) were performed. Electrocardiography was performed before CUS (Day 0), Day 20, and Day 40 to study electrocardiogram parameters. Furthermore, changes in body weight, organ weight, tissue lipid peroxidation, glutathione, catalase, cTn-I, MMP-2, and proinflammatory cytokines (TNF-α and IL-6) were estimated. Our results showed that RA treatment caused a reduction in immobility period, adrenal hyperplasia, corticosterone level, tissue lipid peroxidation, cTn-I, MMP-2, proinflammatory cytokines, and QRS complex duration, while an increase in sucrose consumption, brain serotonin level, T-wave width, glutathione, and catalase activity as compared with the CUS-control group. The results of our study proved that RA administration ameliorates CUS-induced depression-associated cardiac abnormalities in rats via serotonergic, oxidative, and inflammatory pathways.

Ginsenoside F1 attenuates pirarubicin-induced cardiotoxicity by modulating Nrf2 and AKT/Bcl-2 signaling pathways

BackgroundPirarubicin (THP) is an anthracycline antibiotic used to treat various malignancies in humans. The clinical usefulness of THP is unfortunately limited by its dose-related cardiotoxicity. Ginsenoside F1 (GF1) is a metabolite formed when the ginsenosides Re and Rg1 are hydrolyzed. However, the protective effects and underlying mechanisms of GF1 on THP-induced cardiotoxicity remain unclear. MethodsWe investigated the anti-apoptotic and anti-oxidative stress effects of GF1 on an in vitro model, using H9c2 cells stimulated by THP, plus trigonelline or AKT inhibitor imidazoquinoxaline (IMQ), as well as an in vivo model using THP-induced cardiotoxicity in rats. Using an enzyme-linked immunosorbent test, the levels of malondialdehyde (MDA), brain natriuretic peptide (BNP), creatine kinase (CK-MB), cardiac troponin (c-TnT), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione (GSH) were determined. Nuclear factor (erythroid-derived2)-like 2 (Nrf2) and the expression of Nrf2 target genes, including heme oxygenase-1 (HO-1), glutathione-S-transferase (Gst), glutamate-cysteine ligase modifier subunit (GCLM), and expression levels of AKT/Bcl-2 signaling pathway proteins were detected using Western blot analysis. ResultsTHP-induced myocardial histopathological damage, electrocardiogram (ECG) abnormalities, and cardiac dysfunction were reduced in vivo by GF1. GF1 also decreased MDA, BNP, CK-MB, c-TnT, and LDH levels in the serum, while raising SOD and GSH levels. GF1 boosted Nrf2 nuclear translocation and Nrf2 target gene expression, including HO-1, Gst, and GCLM. Furthermore, GF1 regulated apoptosis by activating AKT/Bcl-2 signaling pathways. Employing Nrf2 inhibitor trigonelline and AKT inhibitor IMQ revealed that GF1 lacked antioxidant and anti-apoptotic effects. ConclusionIn conclusion, GF1 was found to alleviate THP-induced cardiotoxicity via modulating Nrf2 and AKT/Bcl-2 signaling pathways, ultimately alleviating myocardial oxidative stress and apoptosis.

Comparing the effect of Centella asiatica L. and Acalypha indica L. treatment to carbonyl and glutathione level in the brains of old rats

Background: Free radicals in excessive concentrations damages cells and accelerate the aging process. Antioxidants found in Centella asiatica (CA) and Acalypha indica (AI) have the potential to prevent oxidative cellular damage.&#x0D; Objective: This study aimed to determine the effect of CA and AI on carbonyl and glutathione levels in the brain of older rats.&#x0D; Methods: 18-month age rats were treated using either AI, CA, or vitamin E. In addition, 18-month age and 2-month age untreated rats were used as a negative control. The brain carbonyl and glutathione levels were measured by Agustyanak and the Elmann method, respectively.&#x0D; Results: Treatment with CA significantly decreased brain carbonyl levels (2.87 nmol/mL) than the control rats (4.54 nmol/mL). Furthermore, treating AI did not reduce the brain carbonyl and GSH levels in aged brain rats.&#x0D; Conclusion: Centella asiatica can reduce the protein destruction that occurs with increasing age.

Delayed Impact of 2-Oxoadipate Dehydrogenase Inhibition on the Rat Brain Metabolism Is Linked to Protein Glutarylation.

BackgroundThe DHTKD1-encoded 2-oxoadipate dehydrogenase (OADH) oxidizes 2-oxoadipate—a common intermediate of the lysine and tryptophan catabolism. The mostly low and cell-specific flux through these pathways, and similar activities of OADH and ubiquitously expressed 2-oxoglutarate dehydrogenase (OGDH), agree with often asymptomatic phenotypes of heterozygous mutations in the DHTKD1 gene. Nevertheless, OADH/DHTKD1 are linked to impaired insulin sensitivity, cardiovascular disease risks, and Charcot-Marie-Tooth neuropathy. We hypothesize that systemic significance of OADH relies on its generation of glutaryl residues for protein glutarylation. Using pharmacological inhibition of OADH and the animal model of spinal cord injury (SCI), we explore this hypothesis.MethodsThe weight-drop model of SCI, a single intranasal administration of an OADH-directed inhibitor trimethyl adipoyl phosphonate (TMAP), and quantification of the associated metabolic changes in the rat brain employ established methods.ResultsThe TMAP-induced metabolic changes in the brain of the control, laminectomized (LE) and SCI rats are long-term and (patho)physiology-dependent. Increased glutarylation of the brain proteins, proportional to OADH expression in the control and LE rats, represents a long-term consequence of the OADH inhibition. The proportionality suggests autoglutarylation of OADH, supported by our mass-spectrometric identification of glutarylated K155 and K818 in recombinant human OADH. In SCI rats, TMAP increases glutarylation of the brain proteins more than OADH expression, inducing a strong perturbation in the brain glutathione metabolism. The redox metabolism is not perturbed by TMAP in LE animals, where the inhibition of OADH increases expression of deglutarylase sirtuin 5. The results reveal the glutarylation-imposed control of the brain glutathione metabolism. Glutarylation of the ODP2 subunit of pyruvate dehydrogenase complex at K451 is detected in the rat brain, linking the OADH function to the brain glucose oxidation essential for the redox state. Short-term inhibition of OADH by TMAP administration manifests in increased levels of tryptophan and decreased levels of sirtuins 5 and 3 in the brain.ConclusionPharmacological inhibition of OADH affects acylation system of the brain, causing long-term, (patho)physiology-dependent changes in the expression of OADH and sirtuin 5, protein glutarylation and glutathione metabolism. The identified glutarylation of ODP2 subunit of pyruvate dehydrogenase complex provides a molecular mechanism of the OADH association with diabetes.

Pelargonidin ameliorates reserpine-induced neuronal mitochondrial dysfunction and apoptotic cascade: a comparative in vivo study

Background Targeting the neuronal mitochondria as a possible intervention to guard against neurodegenerative disorder progression has been investigated in the current work via the administration of pelargonidin (PEL) to rats intoxicated by the mitochondrial toxin reserpine. The main criteria for choosing PEL were its reported antioxidant, anti-apoptotic and anti-inflammatory activities. Methods Male albino Wistar rats were randomized into five experimental groups; normal control, reserpinized to induce mitochondrial failure, standard PARP-1-inhibitor 1,5-isoquinolinediol (DIQ)-treated reserpinized, PEL-treated reserpinized, and GSK-3β inhibitor (AR-A 014418) -treated reserpinized. Results PEL administration reversed the reserpine-induced abnormal behaviors marked by decreased catalepsy time. In addition, PEL restored brain glutathione with a reduction in nitric oxide content as compared to the reserpine-challenged group. Meanwhile, it improved neuronal mitochondrial function by the elevation of complex I activity associated with a low ADP/ATP ratio. Likely through its anti-inflammatory effect, PEL reduced the elevation of serum interleukin-1ß level and inhibited serum lactate dehydrogenase activity. These findings are aligned with the reduced expression of cleaved PARP and cleaved caspase-3 proteins, indicating PEL’s suppressive effect on the intrinsic apoptotic pathway. Those biochemical findings were confirmed through comparable histopathological tissue examination among the experimental groups. Conclusions In conclusion, PEL is a promising candidate for future use in the management of mitochondria-associated neuronal complications via controlling the ongoing inflammatory and degeneration cascades.

Comparing The Effects of Selenium Nanoparticles and Selenium Nanocomposites on Food Intake and Anxiety-like Behaviors

Background &amp; Objective: Selenium nanoparticles (Se -NPs) and selenium nanocomposites (Se -NCs) have different biological effects. Therefore, the present study aimed to compare the effects of selenium nanoparticles and selenium nanocomposites (Se –NCs) on anxiety, food intake, and brain histology of rats. Materials &amp; Methods: Thirty-two male adult Wistar rats were randomly and equally divided into four groups. The control group received saline, the Selenium powder group received 1 mg/kg /day selenium powder orally for 21 days, and the selenium nanoparticle group received three weeks of oral gavage of Se –NPs. The selenium nanocomposites group received three weeks of oral gavage of nanocomposites. Finally, cumulative food consumption and anxiety-like behaviors were assessed, and, after that, rats were bled and sacrificed for further biochemical and histopathological investigations. Results: Oral administration of Se powder at a dose of 1 mg/kg /day for 21 days had no significant effect on the brain superoxide dismutase (SOD), catalase (CAT) activities. There was also no significant change in the levels of brain glutathione concentration (GSH), brain MDA, and behavioral parameters. Selenium nanoparticles also showed no significant alterations in brain biochemical parameters, behavioral effects, and brain histology. The oral administration of Selenium nanocomposites significantly increased brain superoxide dismutase, catalase, and reduced glutathione content and had positive effects on behavioral parameters. Conclusion: The present study showed that Se -NCs have behavioral effects and could induce significant biochemical changes in brain oxidative status.

Kolaviron, a flavonoid-rich extract ameliorates busulfan-induced chemo-brain and testicular damage in male rats through inhibition of oxidative stress, inflammatory, and apoptotic pathways.

Previous reports revealed that increased oxidative stress with up-regulated inflammatory proteins and apoptotic factors have serious implications in busulfan-induced chemo-brain and testicular damages. Hence, we investigated the potential reversal effects of kolaviron (KV), a neuro-active extract rich in flavonoids with proven anti-oxido-inflammatory and anti-apoptotic properties, on busulfan-induced oxidative damage, inflammatory proteins, and apoptosis in the brains and testes of male rats. In the treatment-regimen, animals in groups 1 and 2 had saline (10ml/kg/p.o./day) and dimethyl sulfoxide (DMSO; 10ml/kg/p.o./day), group 3 received KV extract (200mg/kg/p.o./day), group 4 was given busulfan (50mg/kg/p.o./day) and animals in group 5 were pretreated with busulfan (50mg/kg/p.o./day) successively for 56days in addition to KV extract (200mg/kg/p.o./day) from days 29-56. Non-spatial memory function was valuated with a novel-object recognition memory test. Thereafter, testicular and brain oxidative/antioxidant status, proinflammatory- and apoptotic-related proteins, testicular enzymatic markers were evaluated respectively. Kolaviron extract improved cognitive function by increasing exploration of novel-object of busulfan-treated rats. Kolaviron extract reversed busulfan-mediated increased malondialdehyde, 8-hydroxy-2'-deoxyguanosine, and decreased superoxide dismutase, catalase, glutathione, and glutathione-peroxidase in brains and testes as well as the testicular enzyme markers. Increased brain and testicular weights, and TNF-α, IL-1β, and NF-κβ productions due to busulfan administration were also reduced by the extract. The reduced testicular B-cell lymphoma-2, sperm mitochondrial cytochrome-C, and membrane potential, increased DNA fragmentation, caspases -3 and -9 levels were also profoundly reversed by KV. Additionally, KV extract ameliorated busulfan-induced testicular histopathological changes in rats. Conclusively, KV extract reverses busulfan-induced neuroendopathobiological derangements via oxidative stress inhibition, down-regulation of inflammatory and apoptotic mediators in rats' brains and testes. PRACTICAL APPLICATIONS: Busulfan is an orally effective chemotherapy drug widely used for cancer treatment. It has been reported that chronic usage of busulfan increases the tendency for carcinogenic and teratogenic activities with severe side effects on the functions of the gonads and other body organs such as brain, popularly regarded as chemo-brain. When taken over a prolonged period of time, busulfan causes sterility in animals and destroyed spermatogonial stem cells along with the seminiferous tubules and sperm morphology of animals as well as memory impairments. The findings from the study revealed that KV extract prevent busulfan-induced cognitive and testicular impairments following kolaviron supplementation. Thus, the findings from this scientific investigation suggest that KV extract could improve the quality of reproductive life and cognitive functions of male patients during busulfan chemotherapy, particularly during prolonged therapy.

Experimental validation of Vitex negundo leaves hydroalcoholic extract for neuroprotection in haloperidol induced parkinson's disease in rat.

Parkinsonism is a neurodegenerative disease, mainly imbalance in dopamine and acetylcholine neurotransimitter in mid brain, which manifestation of dysfunctions of extrapyramidal like akinesia, tremor, rigidity and catalepsy etc., even cognitive and memory loss. The current study is framed to evaluate the effect of Vitex negundo (VNL) leaf extract in Haloperidol induced PD in rats. In vitro studies of antioxidant capacity were checked via DPPH and NO assays and identified its Acetylcholinesterase (AChE) inhibitory activity. Secondly the In vivo study of anti-PD activity in Haloperidol induced in rats were evaluated by Rotarod, morris water maze (MWM), cooks pole climb (CPC), actophotometer, novel object recognition (NOR), and T-maze were utilized to assess extrapyramidal, cognitive and memory function. Thirdly, changes in biomarker level viz. (AChE), butyrylcholinesterase. (BChE) in hippocampus and cortex, reduced glutathione (GSH), malondialdehyde (MDA), total protein (TP), superoxide dismutase (SOD), catalase (CAT), and dopamine level in the whole brain were measured. Finally, histopathology of hippocampus and cortex was examined at 40x magnification to access restoring integrity and maintaining the architecture of neuronal cell in the treatment group compared to control group and L-DOPA as a standard treatment group. V. negundo showed potent antioxidant potency on scavenging of DPPH (IC50 84.81μg/ml) and NO (IC50 133.20μg/ml) and possess AChE inhibitory potency (IC50 114.35μg/ml) by in vitro studies. The Rotarod, MWM, CPC, Actophotometer, NOR, T-maze demonstrated that Haloperidol group administration declines performance time, ELT, TL and decreases locomotion, cognitive and memory respectively. The treatment of VNL 100, 200, and 400mg/kg p.o. significantly (p < 0.05 to p < 0.0001) reversed. Whole brain AChE, BChE, and MDA level were significantly raised and GSH, TP, SOD, CAT and Dopamine were significantly declined in Haloperidol treated group rats, especially V. negundo 400mg/kg p.o. highly significantly ameliorate the Haloperidol group altered pathological changes through the restoration of the cholinergic function, enhancing the antioxidant defense and by increasing the dopaminergic function. The current study provides validation of V. negundo for its anti-PD activity and could be a valuable source for the treatment of PD in future.

Assessment of In Vitro Tests as Predictors of the Antioxidant Effects of Insulin, Metformin, and Taurine in the Brain of Diabetic Rats.

Hyperglycemia-induced oxidative stress is an intrinsic feature of diabetes mellitus and a recognized causative factor of complications associated with the disease. As a result, compounds possessing antioxidant properties are commonly investigated as possible ways of minimizing and even preventing diabetes-related oxidative stress. On these premises, the present study was carried out to investigate the antioxidant properties of metformin (MET), a common oral hypoglycemic agent, of taurine (TAU), a sulfonic acid compound with known antioxidant benefits in diabetes, and of insulin (INS), a standard antidiabetic serving as a reference compound, by using in vitro and in vivo tests. A battery of seven in vitro tests was used to assess antioxidant/antiradical activity. The addition of a treatment compound led to a meanpercentage decrease of values for free radical/lipid peroxidation (LPO) that ranged from very high (82%) with INS to moderate (43%) with MET) and to low (31%) with TAU. Combining MET with TAU leads to an improvement of the effect seen with MET alone (46%). By contrast, under the same conditions, N-acetylcysteine, a known antioxidant, was more potent (92%) than any of the test compounds. In vivo studies were conducted using rats made diabetic with streptozotocin and treated with daily doses of INS, MET, TAU, and MET-TAU for 6weeks. Among the test compounds, the greatest hypoglycemic effect was attained with INS (>90% decrease), followed by MET (~70% decrease), with TAU providing only a modest effect (-30% decrease). Unexpectedly, however, all three compounds reduced the diabetic values for brain LPO, nitric oxide, antioxidant enzymes, glutathione, and glutathione-related enzymes to values that varied in extent within a narrow range (<12% from one another). On the other hand, pairing MET with TAU led to a small enhancement (<10%) of the effects seen with MET alone. In short, while in vitro tests for antioxidant/antiradical activity suggest marked differences in potency for INS, MET, and TAU as a result of different structures, changes in the values of indices of oxidative stress affected by these compounds in the brain of diabetic rats varied within a rather narrow range. Also, the present results suggest that although hyperglycemia is an important determinant of the oxidative stress of diabetes, other factors may be involved since a weak hypoglycemic like TAU demonstrated in vivo antioxidant actions that were comparable to those of more potent hypoglycemic agents like INS and MET.

Anticonvulsant and antioxidant effect of hydroalcoholic extract of Valeriana wallichii rhizomes in acute and chronic models of epilepsy in albino rats

Oxidative stress plays an important role in the aetiology of seizure-induced neuronal death. The present study was aimed to evaluate the anticonvulsant and antioxidant activity of hydroalcoholic extract of Valeriana wallichii (HAEVW) rhizomes in albino rats. Flavonoids possess a potent anticonvulsant effect through modulation of GABA/BDZ receptor and neuroprotective effect by regulating oxidative stress in PTZ-induced convulsion. Total phenolics and flavonoids content of HAEVW rhizomes were measured and the anticonvulsant activity was evaluated using PTZ and MES induced convulsion models. The in-vivo antioxidant activity was evaluated using the PTZ-kindled model by estimating brain malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and nitric oxide (NO). It was observed that the flavonoids content of the extract was 80% of the total phenolics content and HAEVW (200 and 400 mg/kg) showed a significant (P <0.01) delay in onset, decrease in duration of tonic convulsion and hind limb tonic extension (HLTE) in PTZ and MES induced convulsion respectively. In the PTZ-kindling model, HAEVW rhizomes (400 mg/kg) restored the MDA and all antioxidant parameters to normal except NO. It was concluded that flavonoids of rhizomes of V. wallichii may be responsible for the anticonvulsant and antioxidant activity of the extract.