scholarly journals Aryl hydrocarbon receptor antagonism before reperfusion attenuates cerebral ischaemia/reperfusion injury in rats

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jae-Im Kwon ◽  
Hwon Heo ◽  
Su Jeong Ham ◽  
Yeon Ji Chae ◽  
Do-Wan Lee ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Cerebral Ischaemia ◽  
Cellular Damage ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Control Group ◽  
Neuroprotective Effects ◽  
Infarct Region ◽  
Treatment Groups ◽  
Aryl Hydrocarbon ◽  
Apparent Diffusion Coefficient Values

Abstract Aryl hydrocarbon receptor (AhR) antagonism can mitigate cellular damage associated with cerebral ischaemia and reperfusion (I/R) injury. This study investigated the neuroprotective effects of AhR antagonist administration before reperfusion in a rat stroke model and influence of the timing of AhR antagonist administration on its neuroprotective effects. Magnetic resonance imaging (MRI) was performed at baseline, immediately after, and 3, 8, and 24 h after ischaemia in the sham, control (I/R injury), TMF10 (trimethoxyflavone [TMF] administered 10 min post-ischaemia), and TMF50 (TMF administered 50 min post-ischaemia) groups. The TMF treatment groups had significantly fewer infarcts than the control group. At 24 h, the relative apparent diffusion coefficient values of the ischaemic core and peri-infarct region were significantly higher and relative T2 values were significantly lower in the TMF10 groups than in the control group. The TMF treatment groups showed significantly fewer terminal deoxynucleotidyl transferase dUTP nick-end labelling positive (+) cells (%) in the peri-infarct region than the control group. This study demonstrated that TMF treatment 10 or 50 min after ischaemia alleviated brain damage. Furthermore, the timing of AhR antagonist administration affected the inhibition of cellular or vasogenic oedema formation caused by a transient ischaemic stroke.

scholarly journals Study and Determination of Aryl Hydrocarbon Receptor with Some Trace Elements in Fuel Filling Station Workers

2020 ◽  
Vol 10 (4) ◽  
pp. 233-251
Author(s):  
Bassem Abd Al-Raheem Twaij ◽  
Dr. Muthana Salam Mashkour ◽  
Dr.Hussein Kadhem Al-Hakeim
Keyword(s):  
Trace Elements ◽  
Serum Concentration ◽  
Aryl Hydrocarbon Receptor ◽  
Negative Correlation ◽  
Aromatic Hydrocarbons ◽  
Significant Negative Correlation ◽  
Correlation Study ◽  
Control Group ◽  
Aryl Hydrocarbon ◽  
Filling Station

PollutiOn is the intrOduction Of contaminantsʹ intO the natural envirOnment that cause adverseʹ change. Gasoline is a toxic and highly flammable liquid consists of various types of aliphatic hydrocarbons, olefins, benzenes and aromatic hydrocarbons including toluene, xylene and a large number of volatile compounds in addition to tetraethyl lead. Gasoline consists of different types of aliphatic hydrocarbons, aryl compounds and some trace elements. Trace elements are several important roles in human bodies, some are essential for enzymes reactions where they attract and facilitate conversion of substrate molecules to specific end products. Aryl hydrocarbon receptor (AHR) is a receptor involved in the regulation of biological responses to planar aromatic hydrocarbons.       The aim of the present study is to compare the serum AHR level in the fuel station workers (FSW) with the non-workers as a control group. The other aim is to find out a possible correlation between AHR with trace elements.              Sixty male FSW and 30 controls, from ten fuel stations at Al-Najaf City-Iraq, were participated in the present study. The AHR level in serum was measured using ELISA technique. Determine the following metal ions Zn2+, Cu2+, Fe3+, Mg2+, Na+ and K+ level in filling station workers (FSW) and control group were measured spectrophotometrically by using ready for use kits. Serum Pb level was carried out using Atomic absorption spectroscopy.              The results serum concentration of AHR in FSW group revealed a significant increase (p<0.001) as compared with the control group. No significant difference was noticed in AHR as compered in exposure ≥12years with exposure <12years in FWS. Smoking has no significant correlation with other parameters. Correlation study indicated a correlation between AHR and Age. Serum concentration of Cu2+, Zn2+, K+ and Pb in FSW group revealed a significant increase (p<0.001) as compared with the control group. While Fe3+, Na+ and Mg2+ in FSW group revealed a significant decrease (p<0.001) as compared with the control group. Correlation study indicated a significant negative correlation between serum Pb and AHR while other trace elements showed no significant correlation with AHR in FSW group. There is a significant negative correlation between serum Cu2+ with age while there is significant increase correlation between Zn2+, Mg2+ and Pb with age in FWS group.                 Conclusion of study is The role of increase AHR on the health in FSW group, attention to use safety gloves and face mask is recommended for FSW and a long follow-up to the studied group is necessary to explore the    prognosis of increase AHR in FSW.  

scholarly journals Upregulation of Antioxidant Gene Expressions and Enzyme Activity Against Acrylamide-Induced Neurotoxicity in Mice after Grape Seed Extract Treatment

2020 ◽  
Vol 14 (1) ◽  
pp. 23-31
Author(s):  
Sarah Albogami
Keyword(s):  
Grape Seed Extract ◽  
Grape Seed ◽  
Seed Extract ◽  
Control Group ◽  
Gene Expressions ◽  
Neuroprotective Effects ◽  
Treatment Groups ◽  
Biochemical Assays ◽  
Test Parameters

Background: The risk of occupational exposure to acrylamide is high and long-term acrylamide exposure can cause neurotoxicity. Thus, therapeutic agents that can protect against acrylamide-induced neurotoxicity are needed. Objective: To investigate whether Grape Seed Extract (GSE) protects against acrylamide-induced neurotoxicity in mice. Methods: Mice were divided into saline, GSE, acrylamide, GSE followed by acrylamide, acrylamide followed by GSE, and simultaneous acrylamide and GSE treatment groups. Gene expression and antioxidant enzyme levels were then determined using RT-PCR and biochemical assays. Results: Gpx1 (P < 0.05), Prdx3 (P < 0.01), SOD1 (P < 0.05), and CAT (P < 0.05) significantly upregulated in GSE-treated mice, compared to those in untreated controls. In contrast, Gpx1 (P < 0.05), Prdx3 (P < 0.05), SOD1 (P < 0.05), and CAT (P < 0.05) significantly downregulated in acrylamide-treated mice compared to those in untreated controls. Results of the treatment with GSE before exposure to acrylamide or simultaneously with acrylamide indicated that GSE restored Gpx1, Prdx3, SOD1, and CAT expression to similar levels as those in the control group. GSE treatment after exposure to acrylamide did not exert any neuroprotective effects against acrylamide, as revealed by significant downregulation of Gpx1 (P < 0.05), Prdx3 (P < 0.01), SOD1 (P < 0.05), and CAT (P < 0.05) compared to that in untreated controls. Animals treated with grape seed before acrylamide treatment showed no significant change in LPO activities and a significant increase in GSH levels, compared to those in untreated controls. Conclusion: GSE exerted neuroprotective effects against acrylamide-induced neurotoxicity. Acrylamide caused oxidative stress 20 days post-exposure. However, grape seed treatment before exposure to acrylamide restored all test parameters to levels similar to control values.

scholarly journals Sevoflurane Preconditioning against Focal Cerebral Ischemia

2009 ◽  
Vol 110 (6) ◽  
pp. 1271-1278 ◽  
Author(s):  
Jean-Laurent Codaccioni ◽  
Lionel J. Velly ◽  
Chahrazad Moubarik ◽  
Nicolas J. Bruder ◽  
Pascale S. Pisano ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Cerebral Injury ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Control Group ◽  
Sprague Dawley ◽  
Nissl Staining ◽  
Neuroprotective Effects ◽  
Sevoflurane Preconditioning

Background Preconditioning the brain with volatile anesthetics seems to be a viable option for reducing ischemic cerebral injury. However, it is uncertain whether this preconditioning effect extends over a longer period of time. The purpose of this study was to determine if sevoflurane preconditioning offers durable neuroprotection against cerebral ischemia. Methods Rats (Sprague-Dawley) were randomly allocated to two groups: nonpreconditioned control group (n = 44) and preconditioned group (n = 45) exposed to 2.7 vol% sevoflurane (45 min) 60 min before surgery. Animals in both groups were anesthetized with 3.0 vol% sevoflurane and subjected to transient middle cerebral artery occlusion. After 60 min of awake focal ischemia, the filament was removed. Functional neurologic outcome (range 0-18; 0 = no deficit), cerebral infarct size (Nissl staining), and apoptosis (Terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling; cleaved caspase-3 staining) were evaluated at 3, 7, and 14 days after ischemia. Results Sevoflurane preconditioning significantly improved functional outcome and reduced infarct volume (109 +/- 43 vs. 148 +/- 56 mm(3)) 3 days after ischemia compared to the control group. However, after 7- and 14-day recovery periods, no significant differences were observed between groups. The number of apoptotic cells was significantly lower in the preconditioned group than in the control group after 3- and 7-day recovery periods. Fourteen days after ischemia, no differences were observed between groups. Conclusion In this model of transient focal cerebral ischemia, sevoflurane preconditioning induced effective but transient neuroprotective effects. Sevoflurane preconditioning also decreased ischemia-induced apoptosis in a more sustained way because it was observed up to 7 days after injury.

scholarly journals Prenatal indole-3-carbinol administration activates aryl hydrocarbon receptor-responsive genes and attenuates lung injury in a bronchopulmonary dysplasia model 

2020 ◽  
pp. 153537022096378
Author(s):  
Gabriela Guzmán-Navarro ◽  
Mario Bermúdez de León ◽  
Irene Martín-Estal ◽  
Raquel Cuevas-Díaz Durán ◽  
Laura Villarreal-Alvarado ◽  
...  
Keyword(s):  
Lung Injury ◽  
Aryl Hydrocarbon Receptor ◽  
Signaling Pathway ◽  
Bronchopulmonary Dysplasia ◽  
Quantitative Polymerase Chain Reaction ◽  
Control Group ◽  
Hypoxia Exposure ◽  
Unexposed Control ◽  
Aryl Hydrocarbon ◽  
Rat Pups

Hyperoxia−hypoxia exposure is a proposed cause of alveolar developmental arrest in bronchopulmonary dysplasia in preterm infants, where mitochondrial reactive oxygen species and oxidative stress vulnerability are increased. The aryl hydrocarbon receptor (AhR) is one of the main activators of the antioxidant enzyme system that protects tissues and systems from damage. The present study aimed to determine if the activation of the AhR signaling pathway by prenatal administration of indole-3-carbinol (I3C) protects rat pups from hyperoxia–hypoxia-induced lung injury. To assess the activation of protein-encoding genes related to the AhR signaling pathway ( Cyp1a1, Cyp1b1, Ugt1a6, Nqo1, and Gsta1), pup lungs were excised at 0, 24, and 72 h after birth, and mRNA expression levels were quantified by reverse transcription-quantitative polymerase chain reaction assays (RT-qPCR). An adapted Ratner's method was used in rats to evaluate radial alveolar counts (RACs) and the degree of fibrosis. The results reveal that the relative expression of AhR-related genes in rat pups of prenatally I3C-treated dams was significantly different from that of untreated dams. The RAC was significantly lower in the hyperoxia–hypoxia group (4.0 ± 1.0) than that in the unexposed control group (8.0 ± 2.0; P <  0.01). When rat pups of prenatally I3C-treated dams were exposed to hyperoxia–hypoxia, an RAC recovery was observed, and the fibrosis index was similar to that of the unexposed control group. A cytokine antibody array revealed an increase in the NF-κB signaling cascade in I3C-treated pups, suggesting that the pathway could regulate the inflammatory process under the stimulus of this compound. In conclusion, the present study demonstrates that I3C prenatal treatment activates AhR-responsive genes in pup’s lungs and hence attenuates lung damage caused by hyperoxia–hypoxia exposure in newborns.

Neuroprotective effect of gastrodin in methamphetamine-induced apoptosis through regulating cAMP/PKA/CREB pathway in cortical neuron

2020 ◽  
Vol 39 (8) ◽  
pp. 1118-1129
Author(s):  
C-L Ma ◽  
L Li ◽  
G-M Yang ◽  
Z-B Zhang ◽  
Y-N Zhao ◽  
...  
Keyword(s):  
Small Interfering Rna ◽  
Neuronal Cells ◽  
Cell Counting ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Control Group ◽  
Protective Mechanism ◽  
Apoptotic Cells ◽  
Neuroprotective Effects ◽  
Expression Levels ◽  
Interfering Rna

Objective: Methamphetamine (MA) abuse induces neurotoxicity and causes neuronal cell apoptosis. Gastrodin is a traditional Chinese herbal medicine used for the treatment of nerve injuries, spinal cord injuries, and some central nervous system diseases as well. The present study investigated the neuroprotective effects of gastrodin against MA-induced neurotoxicity in neuronal cells and its potential protective mechanism. Methods: The primary cortex neuronal culture was divided into four groups (control group, MA group, MA + gastrodin group, and MA + gastrodin + small interfering RNA group). The neurotoxicity of MA was assessed by detecting apoptotic cells by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay and cell viability by cell counting kit 8 (CCK-8) method, the Tuj1-positive cells and the average axonal length were detected by immunofluorescence, and the expressions of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP-response element-binding (CREB), and brain-derived neurotrophic factor (BDNF) proteins were detected by Western blot. Results: The results of CCK-8 assay showed that 0.5 mM MA was an optimal concentration that induced neurotoxicity ( p < 0.01). Pretreatment with 25 mg/L gastrodin exerted maximum protective effects on neuronal cells. The expression levels of cAMP, PKA, phosphorylated PKA, CREB, phosphorylated CREB, and BDNF proteins were decreased in the MA group, and pretreatment with gastrodin upregulated the expression levels of these proteins ( p < 0.01). The expressions of PKA and CREB proteins showed no significant changes in the control group, MA group, and gastrodin group. Compared the MA + gastrodin + small interfering RNA group with MA + gastrodin group, the Tuj1-positive cells and the average axonal length were decreased significantly, while the number of apoptotic cells was increased ( p < 0.05). Conclusion: Gastrodin has neuroprotective effects against MA-induced neurotoxicity, which exerts neuroprotective effects via regulation of cAMP/PKA/CREB signaling pathway and upregulates the expression of BDNF.

The Protective Effect of Sulfated Pachymaran on 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Neuronal Apoptosis in Mice

2017 ◽  
Vol 17 (1) ◽  
pp. 64-68
Author(s):  
Gao Gui-Zhen ◽  
Wu Chao ◽  
Zhai Ke-Feng ◽  
Shan Ling-Ling ◽  
Li Mei-Hong
Keyword(s):  
Tyrosine Hydroxylase ◽  
Protective Effect ◽  
Neuronal Apoptosis ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Nigrostriatal Pathway ◽  
Neuroprotective Effects ◽  
Treatment Groups ◽  
Induced Apoptosis ◽  
Different Doses

Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine were used to examine the neuroprotective effects of sulfated pachymaran. Male ICR mice were administered 30 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intraperitoneally once a day for 7 days in model group. In sulfated pachymaran treatment groups, different doses of sulfated pachymaran (50, 100, and 150 mg/kg, respectively) were given consecutively after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment in the following 7 days. The apoptosis of neurons in substantia nigra was observed by tyrosine hydroxylase immunostaining and TUNEL (Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) staining. Expression of Bcl-2, and Bax proteins in midbrain and striatum were detected by Western blot. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment significantly decreased the tyrosine hydroxylase-immunoreactive neurons (P < 0.01), increased the TUNEL-positive neurons (P < 0.05). 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine markedly induced downregulation of Bcl-2 expression (P < 0.05, P < 0.01, respectively) and upregulation of Bax (P < 0.05, P < 0.01, respectively) expression in both midbrain and striatum. Sulfated pachymaran restored 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neuronal death in the nigrostriatal pathway, and significantly elevated Bcl-2 expression and declined Bax expression, contributing to the balance between Bcl-2 and Bax proteins. These results indicated that sulfated pachymaran had protective effect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced apoptosis in striato-nigral system in vivo.

Changes of IL-4 and IFN-g expression in monocytes and T-helper lymphocytes while modeling of systemic juvenile idiopathic arthritis in Wistar rats

2018 ◽  
pp. 61-69
Author(s):  
В.Н. Сахаров ◽  
П.Ф. Литвицкий ◽  
Е.И. Алексеева ◽  
Н.А. Маянский ◽  
Р.Ш. Закиров
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Peripheral Blood Mononuclear Cells ◽  
Wistar Rats ◽  
Mononuclear Cells ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Treatment Groups ◽  
Blood Mononuclear Cells ◽  
T Helpers

Цель исследования - изучение перепрограммирования мононуклеарных лейкоцитов на модели системного ювенильного идиопатического артрита (сЮИА), воспроизводимой у крыс Wistar с использованием полного адъюванта Фрейнда и липополисахарида. Методика. сЮИА воспроизведен у 6-месячных крыс-самцов Wistar. На 40-е сут. эксперимента животные были разделены на 3 группы: 1-я группа - контроль; 2-я - группа доксициклина; 3-я - группа дексаметазона. Взятие проб крови у животных проводили на нулевые, 41-е и 55-е сут. Мононуклеарные клетки периферической крови выделяли гравиметрически, после чего окрашивали их на маркеры и внутриклеточные цитокины. Дифференцировали моноциты (CD3-CD4+) и Т-хелперы (CD3+CD4+). Анализировали динамику внутриклеточной экспрессии интерлейкина IL-4 (рассматривали как маркер про-М2 фенотипа, так как в случае выделения из клетки ИЛ-4 служит стимулятором М2 поляризации макрофагов) и IFN-g (как маркер про-М1 фенотипа) по данным проточной цитофлуориметрии. Применяли непараметрический статистический тест Mann-Whitney-Wilcoxon в программе R для статистической обработки данных. Результаты и заключение. При моделировании сЮИА выявлено закономерное изменение фенотипа моноцитов. Применение же доксициклина и дексаметазона приводило к более ранней поляризации их по про-М2-пути в отношении моноцитов (на 41-е сут.) в сравнении с контролем. Про-М1 эффект (на 55-е сут., в сравнении с контролем) выявлен также в группах доксициклина и дексаметазона. У животных разных групп обнаружены характерные динамические изменения внутриклеточной экспрессии цитокинов. Важно, что различная направленность поляризации фенотипа при сЮИА и применении препаратов наблюдается не только у моноцитов, но и у Т-хелперов. The study objective was to evaluate targeted reprogramming of peripheral blood mononuclear cells in systemic juvenile idiopathic arthritis (sJIA) modeled in 6-month-old male Wistar rats by co-administration of complete Freund’s adjuvant and lipopolysaccharide. Methods. On day 40 of the experiment, rats were divided into three groups: control, doxycycline, and dexamethasone groups. Blood samples were collected on days 0, 41, and 55. Peripheral blood mononuclear cells were isolated gravimetrically and stained for markers and cytokines. Monocytes (CD3-CD4+) and T-helpers (CD3+CD4+) were differentiated as target cells. IL-4 was considered a marker for the pro-M2 phenotype since IL-4 can activate M2 macrophage polarization; IFN-g was considered a marker for the pro-M1 phenotype. Time-related changes in the intracellular expression of IL-4 and IFN-g were studied using flow cytometry. Data were analyzed using nonparametric statistical tests (Mann-Whitney-Wilcoxon) in the R environment for statistical computing. Results and conclusions. Monocytes (like macrophages) underwent reprogramming during the development of modeled sJIA disease. In monocytes of doxycycline and dexamethasone treatment groups, pro-M2 effects were observed earlier (day 41) than in the control group. Pro-M1 effects were observed in monocytes of doxycycline and dexamethasone groups on day 55, as compared with the control group. Characteristic time-related changes of intracellular cytokine expression were described for different groups. Importantly, the differently directed phenotype polarization was observed in sJIA and treatment groups for both monocytes and T-helpers.

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