A Study of Emotion Regulation Difficulties, Repetitive Negative Thinking, and Experiential Avoidance in Adults with Stuttering: A Comparative Study.

Objective: Stuttering is a type of communication and fluency disorder that hurts mental and emotional health. It is also associated with a significant increase in both trait and social anxiety. Studies on stuttering in adults have indicated the nature and impact of this phenomenon. In addition, some psychological aspects of this phenomenon remain vague and need further investigation. Therefore, the present study aimed to compare emotion regulation difficulties, repetitive negative thinking, and experiential avoidance between people who stutter and healthy individuals. Method : In this study, 101 people who stutter (43 females and 58 males, with a mean age of 29.55 ± 187 years), as well as 110 healthy individuals (74 females and 36 males, with a mean age of 25.57 ± 489 years) as participants were chosen using the convenience sampling method among those who referred to the speech therapy clinics of Tehran, Iran. Research instruments including the repetitive negative thinking inventory, Difficulties in Emotion Regulation Scale, and Acceptance and Action Questionnaire (AAQ-I) were used for data collection. Data were analyzed using multivariate ANOVA test and Multiple Regression Analysis. Results: The mean age of the participants was 29.55 years in the people who stutter and 25.57 years in the healthy individuals (P < 0.01). The present results indicated that the mean score of experiential avoidance was higher in the people who stutter (M ± SD: 35.74 ± 9.24) compared to the healthy individuals (M ± SD: 8.89 ± 31.11). Additionally, the mean score of emotion regulation difficulties was higher in the people who stutter (M ± SD: 88.75 ± 20.59) compared to the healthy individuals (M ± SD: 64.14 ± 94.94) (P < 0.001). However, there was no significant difference in the mean score of repetitive negative thinking between the people who stutter (M ± SD: 98.45 ± 25.85) and healthy individuals (M ± SD: 93.71 ± 25.24) groups (P > 0.05). There was a significant correlation between experiential avoidance and emotion regulation difficulties in people who stutter (P < 0.01). Experiential avoidance and repetitive negative thinking can significantly predict emotion regulation difficulties in people who stutter (R = 0.65, P < 0.01). Conclusion: People who stutter obtained higher emotion regulation difficulties and experiential avoidance scores than those without stuttering and A significant correlation between experiential avoidance and emotion regulation difficulties was found. Future studies should consider the role of emotion regulation difficulties and experiential avoidance in people who stutter.

Mitochondrial Transportation, Transplantation, and Subsequent Immune Response in Alzheimer's Disease: An Update.

Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by memory impairment and a progressive decline in cognitive function. Mitochondrial dysfunction has been identified as an important contributor to the development of AD, leading to oxidative stress and energy deficits within the brain. While current treatments for AD aim to alleviate symptoms, there is an urgent need to target the underlying mechanisms. The emerging field of mitotherapy, which involves the transplantation of healthy mitochondria into damaged cells, has gained substantial attention and has shown promising results. However, research in the context of AD remains limited, necessitating further investigations. In this review, we summarize the mitochondrial pathways that contribute to the progression of AD. Additionally, we discuss mitochondrial transfer among brain cells and mitotherapy, with a focus on different administration routes, various sources of mitochondria, and potential modifications to enhance transplantation efficacy. Finally, we review the limited available evidence regarding the immune system's response to mitochondrial transplantation in damaged brain regions.

The Effect of Donor Rat Gender in Mitochondrial Transplantation Therapy of Cisplatin-Induced Toxicity on Rat Renal Proximal Tubular Cells.

Background: Cisplatin-induced nephrotoxicity has been linked to a fundamental mechanism of mitochondrial dysfunction. A treatment called mitochondrial transplantation therapy can be used to replace damaged mitochondria with healthy mitochondria. Mitochondrial-related diseases may benefit from this approach. Objectives: We investigated the effect of mitochondrial transplantation on cisplatin-induced nephrotoxicity using freshly isolated mitochondria obtained from renal proximal tubular cells (RPTCs). Methods: Based on our previous findings, we hypothesized that direct exposure of healthy mitochondria to cisplatin-affected RPTCs might improve cytotoxicity markers and restore mitochondrial function. Therefore, the primary objective of this study was to determine whether newly isolated mitochondrial transplantation protected RPTCs from cisplatin-induced cytotoxicity. The supply of exogenous rat kidney mitochondria to cisplatin-affected RPTCs was also a goal of this study to investigate the possibility of gender differences. After the addition of cisplatin (100 µM), rat RPTCs (106 cells/mL) were suspended in Earle's solution (pH = 7.4) at 37°C for two hours. Freshly isolated mitochondria were extracted at 4°C and diluted in 100 and 200 µg/mL mitochondrial protein. Results: Statistical analysis revealed that transplantation of healthy mitochondria decreased ROS level, mitochondrial membrane potential (MMP) collapse, MDA level, glutathione depletion, lysosomal membrane damage, and caspase-3 activity induced by cisplatin in rat RPTCs. In addition, our results demonstrated that transplantation of female rat kidney mitochondria has higher protective activity at reducing toxicity parameters than male mitochondria. Conclusions: The findings reaffirmed that mitochondrial transplantation is a novel, potential, and promising therapeutic strategy for xenobiotic-induced nephrotoxicity.

Allogeneic mitochondrial transplantation ameliorates cardiac dysfunction due to doxorubicin: An in vivo study.

Damage to the mitochondria may lead to serious conditions that are difficult to treat. Doxorubicin is one of the most widely used chemotherapeutic drugs for the treatment of malignancies in children and adults, and reportedly causes damage to the mitochondria. Unfortunately, the dangerous cardiac side effects of doxorubicin appear when the patient is in the midst of a vigorous fight against the disease, either by taking doxorubicin alone or in combination with other drugs. This study aimed to determine whether exogenous healthy and functional mitochondria are internalized by cells, can it help the survival of these cells, and can reduce cardiotoxicity. For this purpose, isolated, pure, and functional exogenous mitochondria were injected into the tail vein of a rat model of doxorubicin-induced cardiotoxicity. After that, the heart function of the rats and their antioxidant status, inflammatory markers, and histopathological examination were investigated. Our findings show that intravenous mitochondrial transplantation provided efficient mitochondrial uptake and reduced cardiotoxicity by reducing ROS production, lipid peroxidation, and inflammation. In addition, the levels of ATP and antioxidant enzymes increased after mitochondrial transplantation; therefore all of these complex processes resulted in the reduction of apoptosis and necrosis in rat heart tissue. These promising results open the way to more effective cancer treatment without the side effects of related drugs. Transplanting exogenous mitochondria probably enhances the cell's mitochondrial network, potentially treating mitochondria-related disorders such as cardiovascular and neurodegenerative diseases, although the exact relationship between mitochondrial damage and these conditions remains unclear.

Laboratory Comparison of Low-Cost Particulate Matter Sensors to Measure Transient Events of Pollution-Part B-Particle Number Concentrations.

Low-cost Particulate Matter (PM) sensors offer an excellent opportunity to improve our knowledge about this type of pollution. Their size and cost, which support multi-node network deployment, along with their temporal resolution, enable them to report fine spatio-temporal resolution for a given area. These sensors have known issues across performance metrics. Generally, the literature focuses on the PM mass concentration reported by these sensors, but some models of sensors also report Particle Number Concentrations (PNCs) segregated into different PM size ranges. In this study, eight units each of Alphasense OPC-R1, Plantower PMS5003 and Sensirion SPS30 have been exposed, under controlled conditions, to short-lived peaks of PM generated using two different combustion sources of PM, exposing the sensors' to different particle size distributions to quantify and better understand the low-cost sensors performance across a range of relevant environmental ranges. The PNCs reported by the sensors were analysed to characterise sensor-reported particle size distribution, to determine whether sensor-reported PNCs can follow the transient variations of PM observed by the reference instruments and to determine the relative impact of different variables on the performances of the sensors. This study shows that the Alphasense OPC-R1 reported at least five size ranges independently from each other, that the Sensirion SPS30 reported two size ranges independently from each other and that all the size ranges reported by the Plantower PMS5003 were not independent of each other. It demonstrates that all sensors tested here could track the fine temporal variation of PNCs, that the Alphasense OPC-R1 could closely follow the variations of size distribution between the two sources of PM, and it shows that particle size distribution and composition are more impactful on sensor measurements than relative humidity.

Single-mode optical fiber couplers made of fluoride glass.

We demonstrate the first single-mode optical fiber couplers made with ZBLAN optical fiber. Couplers are fabricated using a controlled tapering procedure enabling high reproducibility while limiting glass crystallization. A coupling ratio of up to 41%/59% in cross/through ports with an excess loss of 2.5 dB is obtained at a wavelength of 2.73 µm. In addition, the stability of a coupler with traces of surface crystallization is tested at ambient atmosphere over a period of more than 90 days.

Microplastics in Abiotic Compartments of a Hypersaline Lacustrine Ecosystem.

The study of microplastics in inland water bodies has been growing recently, but there is still insufficient knowledge of the status of microplastics in lacustrine ecosystems, especially saline lakes. Studies have also been conducted on sediment, water, and biological compartments of lakes. In the present study, the status of microplastics in abiotic compartments of the saline Maharloo Lake (Iran) was evaluated for the first time and included surface sediment, lake salt, sludge, lake water, and wastewater. A total of 742 microplastics, mainly clear and fibrous, ranging from 50 to 250 µm in size and composed of polypropylene and polyethylene terephthalate, were identified in 33 samples. Mean microplastic concentrations in solid samples were higher than in liquid ones, with the highest levels (51.7 microplastics kg-1 ) in sludge and the lowest levels in lake salt (10.4 microplastics kg-1 ). The highest microplastic levels were found in the northwest area of the lake, where wastewater effluents from urban, industrial, and agricultural activities discharge into the lake. Inter-relationship assessments of microplastics with hierarchical cluster analysis suggested that differences in the distribution of microplastics with different physical properties in Maharloo Lake are greatly affected by weathering processes and proximity to contaminated hotspots. Our results reveal that the widespread occurrence of microplastics in Maharloo Lake mostly originates from potential plastic sources in urban areas of Shiraz Metropolis and its industrial zone in the vicinity of the study area; thus microplastics are dispersed into the lake via surface runoffs, especially wastewater inflows. Environ Toxicol Chem 2023;42:19-32. © 2022 SETAC.

Betaine protects against sodium arsenite-induced diabetes and hepatotoxicity in mice.

Epidemiological evidence has associated chronic exposure to inorganic arsenic with an increased occurrence of glucose intolerance and diabetes mellitus. Furthermore, inorganic arsenic induces oxidative stress in organs such as the liver. Betaine, as a methyl donor, plays a pivotal role in homocysteine metabolism. Betaine has antioxidant and anti-inflammatory properties. Therefore, the aim of this study was to evaluate the effects of betaine against sodium arsenite-induced diabetes and hepatotoxicity in mice. Forty-eight male mice were divided into 6 groups of 8. Group 1, received distilled water every day for 4 weeks by gavage. Group 2 received 500 mg/kg betaine every day for 4 weeks by gavage. Group 3 was given 10 mg/kg NaAsO2 every day for 4 weeks by gavage. Groups 4, 5, and 6 were co-treated with 125, 250, and 500 mg/kg betaine half an hour before NaAsO2 (10 mg/kg), respectively, daily for up to 4 weeks by gavage. After 28 days of the study, the mice were fasted overnight and on day 29, fasting blood glucose was measured and glucose tolerance test was performed. On day 30, the mice were anesthetized and a blood sample was taken from the heart. Serum factors (alanine aminotransferase, aspartate transaminase, and alkaline phosphatase activities), oxidative stress factors (malondialdehyde and glutathione levels, and the activity of superoxide dismutase, glutathione peroxidase, and catalase enzymes) and hepatic inflammatory factors (nitric oxide and tumor necrosis factor α) were measured. Histopathological studies were also performed on the liver and pancreas. In this study, it was shown that arsenic causes glucose intolerance, and oxidative/inflammatory hepatic damage. Co-administration of betaine prevents hepatotoxicity and glucose intolerance induced by arsenic in mice. Co-treatment of betaine with arsenic improved glucose intolerance and protected the liver against arsenic induced-oxidative damage and inflammation. Betaine at the dose of 500 mg/kg showed better results than the other doses. Accordingly, betaine can be suggested as a therapeutic agent against diabetogenic and hepatotoxic effects of arsenic.

Nonlinear chalcogenide optical fiber couplers.

We demonstrate chalcogenide optical fiber couplers with a power-dependent coupling coefficient. The couplers are designed and fabricated using an As2Se3 fiber and characterized at a wavelength of 1938 nm, leading to a critical power of 126 W, the lowest ever reported for any optical fiber coupler. These nonlinear couplers enable all-optical switching and will be useful for passive mode-locking over a wide wavelength range from the telecommunication band to the mid-infrared.

Amyloid fibril reduction through covalently modified lysine in HEWL and insulin.

Proteins possess a variety of nucleophiles, which can carry out different reactions in the functioning cells. Proteins endogenously and synthetically can be modified through their nucleophilic sites. The roles of these chemical modifications have not been completely revealed. These modifications can alter the protein folding process. Protein folding directly affects the function of proteins. If an error in protein folding occurs, it may cause protein malfunction leading to several neurodegenerative disorders such as Alzheimer's and Parkinson's. In this study, Hen Egg White Lysozyme (HEWL) and bovine insulin, as model proteins for studying the amyloid formation, were covalently attached with 5(6)-thiophenolfluorescein. The amyloid formation of the covalently labeled lysozyme and insulin were compared with the native proteins. Interestingly, the results indicated that the covalent attachment of fluorescein slowed down the amyloid formation of HEWL and insulin significantly. The amyloid formation was examined using Thioflavin T (ThT) fluorescence assay, circular dichroism, FTIR, and gel electrophoresis. Tandem mass spectrometry was employed to identify the sites of covalent modifications in HEWL. It turned out that two surface lysine residues (K97 and K 116) in HEWL were modified. Computational studies, including docking and molecular simulations, revealed that 5(6)-thiophenolfluorescein makes several non-covalent interactions with HEWL residues, including Lys 97, leading to the reduction of the ß-sheet in the protein. Additionally, AFM analysis confirmed the amyloid fibril reduction of lysine-modified bovine insulin and HEWL. Altogether, our results expand mechanistic insights into preventing amyloid formation by providing an approach for reducing amyloid formation by modifying specific lysine residues in the proteins.

Fiber optical parametric oscillator made of soft glass.

Fiber optical parametric oscillators (FOPOs) are compact optical sources of coherent and broadly tunable light compatible with operation in unconventional spectral bands. Highly nonlinear silica fibers have enabled the development of FOPOs in the telecommunication wavelength band, but the strong material absorption of silica glass at wavelengths >2 µm limits its applicability in the mid-infrared (MIR) spectral range. In this work, we overcome this issue and report a FOPO designed entirely out of soft glass fiber. For this purpose, we combine an As2Se3 single-mode fiber coupler, an As2Se3 parametric gain medium, and a low-loss ZBLAN delay fiber to build the first all-fiber laser cavity made of soft glass. Two proof-of-concept FOPOs are presented, one driven by pure parametric gain leading to wavelength-tunable Stokes emission within the range 2.088-2.139 µm, and the other driven by Raman-assisted parametric gain leading to Stokes emission within the range 2.023-2.048 µm. This demonstration is a promising first step toward the development of fully fiberized MIR light sources.

Mitotherapy in doxorubicin induced cardiotoxicity: A promising strategy to reduce the complications of treatment.

AIMS: Doxorubicin is a potent and broad-spectrum antineoplastic medication prescribed for both solid and hematological malignancies. Despite its value, the clinical use of doxorubicin is limited due to cardio-oncologic complication and cardiotoxic adverse effect. Among the mechanisms proposed for its toxicity, mitochondrial dysfunction has gained more attention. Therefore, if damaged mitochondria are replaced by normal efficient mitochondria, cardiac toxicity is expected to be reduced or improved. In this way, we have studied the efficiency of transplantation of freshly isolated rat liver mitochondria in neonatal rat cardiomyocytes that have been damaged by doxorubicin. MATERIALS AND METHODS: For this purpose, isolated mitochondria were characterized using mitochondrial complex II, membrane potential and swelling evaluations, and also fluorescence and electron microscopy. Afterward, the effect of mitotherapy on the damaged cardiomyocytes was investigated by using annexin V/PI staining, MTT, ROS, MMP, lipid peroxidation, GSH and ATP evaluations. KEY FINDINGS AND SIGNIFICANCE: Transplanted mitochondria could remarkably enter the neonatal rat cardiomyocytes. Addition of mitochondria to the damaged cardiomyocytes, significantly increased cell viability by reducing the level of reactive oxygen species and lipid peroxidation, increasing of ∆Ψ, ATP and GSH contents and decreasing of apoptotic and necrotic cell death. Our results showed that mitotherapy has a significant restorative effect on cardiotoxicity induced by doxorubicin, which promises a better future to reduce the complications of cancer treatment.

Assessment of groundwater vulnerability in an urban area: a comparative study based on DRASTIC, EBF, and LR models.

The groundwater vulnerability assessment is known as a useful tool for predicting and prevention of groundwater pollution. This study targets the DRASTIC, evidential belief function (EBF), and logistic regression (LR) models to assess vulnerability in Kabul aquifers, Afghanistan Country. The growth of urban sprawl, groundwater overexploitation, and lack of suitable municipal sewage systems as anthropogenic sources have been the main potential to increase groundwater contaminants such as nitrate in the study area. The vulnerability map has been developed based on various effective factors including altitude, slope (percentage rise), aspect, curvature, land-use type, drainage density, distance from river, annual mean precipitation, net recharge, geology/lithology units, the impact of the vadose zone, aquifer media, depth to water (unsaturated zone), saturated zone, drawdown, and hydraulic conductivity. To identify groundwater pollution, the spatial variation of nitrate concentration data in 2018 was considered indication of groundwater pollution. Based on descriptive statistics, the value of 2.65 mg/l (the median of the pixel values of nitrate map) was selected as a threshold to differentiate the occurrence and non-occurrence of pollution. The groundwater quality data were selected and randomly divided into two datasets for training and validation, including 70% and 30%, respectively. The success-rate and prediction-rate curves were computed based on the receiver operating characteristic (ROC) curve and the area under the curve (AUC) to estimate the efficiency of models. The ROC-AUC of success rates for EBF, LR, and DRASTIC models were estimated to be 67%, 66%, and 52%, respectively. Moreover, the ROC-AUC of the prediction rates of the EBF, LR, and DRASTIC models were obtained 61%, 63%, and 55%, respectively. Based on correlation between mean nitrate concentration and the mean vulnerability indexes in each model, the EBF model is the most compatible with the current developed vulnerability zones as the role of mankind in changing the environment in real conditions in comparison to LR and DRASTIC models.

Vortex-assisted dispersive micro-solid phase extraction based on nanostructured imprinted polymer: A comparison study between spectrophotometric and solution scanometric techniques.

In the present work, methyl red molecularly imprinted polymeric (MR-MIP) nanostructure was synthesized using the precipitation polymerizations for the separation of MR dye from aqueous media. The as-prepared MIP was characterized using colorimetry, infrared (IR) spectroscopy, and scanning electron microscopy (SEM). In addition, vortex-assisted dispersive micro-solid phase extraction (VAD-µSPE) based on MIP nanostructure was accomplished as a simple and efficient method for selective preconcentration of low amounts of MR from aqueous solutions. The effects of important parameters such as pH, adsorbent dose, eluent volume, and vortex adsorption-desorption time on the extraction efficiency were investigated. Two techniques including UV-Vis absorption spectroscopy and solution scanometry were applied for the analysis of MR content, comparatively. In spectrophotometric determination, the highest recovery was observed at pH 3.5 after 5 and 3 min of vortex time in the adsorption and desorption steps. The preconcentration factor of 75 and a wide linear concentration range (0.010 and 2.0 mg.L-1; R2 = 0.996) and low detection limit (LOD = 5.0 µg.L-1) with an acceptable precision (RSD = 3.4 %) was observed, too. Under optimum conditions in scanometric determination, a high preconcentration factor (i.e. 500) and similar linearity (0.010-2.0 mg.L-1; R2 = 0.989) and a low LOD of 3.1 µg.L-1, with the relative standard deviation of 1.4% was observed. Both techniques were used for MR recovery from various aqueous samples, successfully.

In vitro toxic interaction of arsenic and hyperglycemia in mitochondria: an important implication of increased vulnerability in pre-diabetics.

Environmental pollutants and lifestyle both contribute to the rapidly increasing prevalence of type 2 diabetes mellitus (T2DM) worldwide. Evidence suggests that exposure to environmental contaminants such as arsenic is associated with impaired glucose metabolism and insulin signaling. In the present study, isolated rat liver mitochondria (1 mg/ml) were co-exposed to low concentration of arsenic trioxide (ATO) ( IC25 = 40 µM) and hyperglycemic condition (20, 40, 80, 160 mM glucose or 20, 40, 80, 160 mM pyruvate (PYR)). Mitochondrial dehydrogenase activity (complex II), glutathione content (GSH), reactive oxygen species (ROS), lipid peroxidation, mitochondrial membrane potential (ΔΨ), and mitochondrial swelling were then evaluated in the presence of ATO 40 µM and PYR 40 mM. Unexpectedly, glucose alone (20, 40, 80, 160 mM) had no toxic effect on mitochondria, even at very high concentrations and even when combined with ATO. Interestingly, PYR at low concentrations (≤ 10 mM) has a protective effect on mitochondria, but at higher concentrations (≥ 40 mM) with ATO, it decreased the complex II activity and increased mitochondrial ROS production, lipid peroxidation, GSH depletion, mitochondrial membrane damage, and swelling (p < 0.05). In conclusion, PYR but not glucose increased ATO mitochondrial toxicity even at low concentrations. These results suggest that pre-diabetics with non-clinical hyperglycemia, who are inevitably exposed to low concentrations of arsenic through food and water, may develop mitochondrial dysfunction that accelerates their progression to diabetes over time.

Synthesis and antioxidant activities of benzylic bromophenols inclusive of natural products.

The synthesis of natural products 2-(2,3-dibromo-4,5-dihydroxyphenyl)acetic acid (1) and 2-(2,6-dibromo-3,5-dihydroxyphenyl)acetic acid (2) and as well as their derivatives 25 and 26 were carried out by substitution, hydrolysis and demethylation reactions of the corresponding four benzyl bromides. The antioxidant potentials of benzylic acid-derived bromophenols were, for the first time, appraised by several outstanding bioanalytical methods. Besides these, we estimated the antioxidant effects which were studied using the methods of DPPH·, ABTS•+ scavenging activities, ferric (Fe3+) and cupric (Cu2+) ions and Fe3+-TPTZ reducing capacities. Benzylic acid-derived bromophenols were found as effective DPPH•, and ABTS•+ scavengers. The potential antioxidant activities of bromophenol derivatives 1, 2 and 17-28 were compared to standard antioxidants including BHA, BHT, α-Tocopherol, and Trolox, which is a water-soluble analog of vitamin E. We expect that this innovative work will direct future studies exploring the antioxidant properties of food, medicinal, and industrial applications.

A New Approach to Designing High-Sensitivity Low-Dimensional Photodetectors.

Photodetectors fabricated from low-dimensional materials such as quantum dots, nanowires, and two-dimensional materials show tremendous promise based on reports of very high responsivities. However, it is not generally appreciated that maximizing the internal gain may compromise the detector performance at low light levels, reducing its sensitivity. Here, we show that for most low-dimensional photodetectors with internal gain the sensitivity is determined by the junction capacitance. Thanks to their extremely small junction capacitances and reduced charge screening, low-dimensional materials and devices provide clear advantages over bulk semiconductors in the pursuit of high-sensitivity photodetectors. This mini-review describes and validates a method to estimate the capacitance from external photoresponse measurements, providing a straightforward approach to extract the device sensitivity and benchmark against physical limits. This improved physical understanding can guide the design of low-dimensional photodetectors to effectively leverage their unique advantage and achieve sensitivities that can exceed that of the best existing photodetectors.

Arsenic and weight loss: At a crossroad between lipogenesis and lipolysis.

Arsenic is found in soil, food, water and earth crust. Arsenic exposure is associated with chronic diseases such as cancer, cardiovascular disease as well as diabetes. One of complex effects of arsenic is on weight gain or loss. Involvement of arsenic in both weight loss and gain signaling pathways has previously been reported; however, too little attention has been paid to its weight reducing effect. Animal studies exhibited a role of arsenic in weight loss. In this regard, arsenic interference with endocrine system, leptin and adiponectin hormones as well as thermogenesis is more evidence. Apparently, arsenic-induced weight lossis generally meditated by its interaction with thermogenesis. In this review we have discussed the irregularities in metabolic pathways induced by arsenic that can lead to weight loss.

Evaluation of Molecular and Cellular Alterations Induced by Neuropathic Pain in Rat Brain Glial cells.

Neuropathic pain originates from illness or damage of the nervous system and affects the somatosensory system. Recently, many efforts have been made to illuminate the influences of neuropathic pain in different parts of central nervous system (CNS). However, the toxic consequences of neuropathic pain in glial cells, which involve in the control of pain is poorly understood. Therefore, the present study aimed to assess the molecular and cellular effects of neuropathic pain in the glial cells of rat brain. Induction of neuropathic pain in rats was associated with oxidative stress as evident by elevated reactive oxygen species (ROS) formation as well as reversible glutathione (GSH) depletion in the glial cells. Moreover, neuropathic pain caused mitochondrial membrane potential collapse (∆Ψm%), lysosomal membrane rapture, and proteolysis, probably due to ROS-induced MPT pore opening. These toxic events could cause cytochrome c release from intermembrane space into the cytosole and trigger caspase activation pathway. Our finding confirmed that the activity of caspase-3 was significantly increased in the glial cells as a core component of the apoptotic machinery. In conclusion, the neuropathic pain induces ROS generation as the major cause of GSH depletion along with mutual mitochondrial/lysosomal potentiation (cross-talk) of oxidative stress in the glial cells. Subsequently, this toxic cross-talk can induce proteolysis and trigger apoptosis by caspase-3 activation in the glial cells of rat brain.

N-acetylcysteine is more effective than ellagic acid in preventing acrolein induced dysfunction in mitochondria isolated from rat liver.

Acrolein, a common environmental, food, and water pollutant, has been linked to the pathology of several diseases. This toxic substance is an unsaturated aldehyde and a major component of cigarette smoke and also produced during the processing of fat-containing foods. This study aimed to evaluate the protective effect of ellagic acid and N-acetylcysteine (NAC) in acrolein-induced toxicity in mitochondria isolated from the rat liver. The mitochondria were exposed to different concentrations of acrolein for 40 min, then functionality was assessed. Contact with acrolein rapidly and remarkably depleted the intracellular glutathione and antioxidant capacity, because of increased ROS production and lipid peroxidation which may lead to the cell death. Mitochondria were then pre-exposed to different concentrations of ellagic acid, NAC, and IC50 concentration of acrolein. Consistent with the results, acrolein decreased GSH content and increased ROS level and lipid peroxidation, which led to ATP depletion and mitochondrial dysfunction. While ellagic acid has been able to reduce ROS and therefore the permeability of the mitochondrial membrane potential (MMP), presumably via its antioxidant properties, we've not detected its favorable effect on GSH and ATP restoration and also on mitochondrial complex II function. However, NAC strongly decreased ROS, lipid peroxidation and MMP and improved GSH content and complex II activity. These results showed that ellagic acid while reported to possess some cellular protective properties, did not prevent mitochondria from being affected by acrolein during this in vitro study. PRACTICAL APPLICATIONS: Ellagic acid is found in fruits, vegetables, and nuts which are revealed to possess strong antioxidant and protective properties. Mitochondrial dysfunction has been implicated in the pathogenesis of some chronic diseases including cancer, diabetes, liver disease, and neurodegenerative disorders, and presumably, ellagic acid by its mitochondrial protective effects can be helpful in these chronic conditions. Acrolein is an α,ß-unsaturated aldehyde that can be produced during cooking at high temperature. By increasing the ROS level and lipid peroxidation and depleting the glutathione content, acrolein induces cellular damage and mitochondrial toxicity. This toxicant is taken into account as a carcinogen and mutagen. In this study, the protective effect of ellagic acid in comparison with N-acetylcysteine has been investigated during the toxicity of acrolein in the rat liver mitochondria to look for evidence of whether it is useful or not through this insult.