scholarly journals Montelukast protects against testes ischemia/reperfusion injury in rats

2013 ◽  
Vol 4 (3) ◽  
pp. 174
Author(s):  
Hulya Ozturk ◽  
Hayrettin Ozturk ◽  
Kaan Gideroglu ◽  
Hakan Terzi ◽  
Guler Bugdayci
Keyword(s):  
Testicular Torsion ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Treated Group ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Group 3 ◽  
Group 2 ◽  
Examen Histologique ◽  
Testicular Injury

Introduction: In this study, we investigate the effect of montelukaston histologic damage induced by testicular torsion-detorsion in rats.Methods: Twenty-one male Sprague-Dawley rats were separatedinto 3 groups, each containing 7 rats. A sham operation was performedin group 1 (control). In group 2 (ischemia-reperfusion [IR]/untreated), 1-hour detorsion of the testis was performed after6 hours of unilateral testicular torsion. In group 3 (I-R/dextroamphetamine),after performing the same surgical procedures as ingroup 2, montelukast was given intraperitoneally. In all experimentalrats, ipsilateral orchiectomies were performed for histologicalexamination and tissue malondialdehyde (MDA), glutathioneand myeloperoxidase assays.Results: Montelukast treatment significantly decreased the I-Rinducedelevation in testes tissue MDA and glutathione levelswere found to be preserved. The level of myeloperoxidase (MPO)activity was significantly increased in the testes tissue of the IR/untreated group. However, in I-R/montelukast treatment groupsignificantly decreased testes tissue MPO level. Histopathologically,the in the group 2 rats, edema, congestion, hemorrhage betweenseminiferous tubules and necrosis of the germinal cells were predominantfeatures in sections. However, most of the specimensin the montelukast treated group 3 showed grades-I and II injury.Additionally, the testicular injury score was lower in group 3 ratscompared with group 2.Conclusion: The current findings demonstrate that the montelukastdecreased the severity of testicular injury by reversing the oxidativeeffects of testes I-R.Introduction : Dans cette étude, nous examinons l’effet du montélukastsur les lésions tissulaires provoquées par torsion-détorsiontesticulaire chez le rat.Méthodologie : Vingt-et-un rats Sprague-Dawley mâles ont étérépartis en trois groupes de 7 rats. Une opération fictive a étéréalisée dans le groupe 1 (groupe témoin). Dans le groupe 2(ischémie-reperfusion / non traité), une détorsion testiculaire d’uneheure a été réalisée après 6 heures de torsion testiculaire unilatérale.Dans le groupe 3 (ischémie-reperfusion / dextroamphétamine),on a administré du montélukast par voie intrapéritonéaleaprès les mêmes interventions chirurgicales que pour le groupe 2.Chez tous les rats, une orchidectomie homolatérale a été effectuéeen vue d’un examen histologique et de mesures du malonaldéhyde,du glutathion et de la myéloperoxidase dans les tissus.Résultats : Le traitement par montélukast a significativement réduitl’élévation dans les tissus testiculaires provoquée par l’ischémiereperfusion,mais les taux de malonaldéhyde et de glutathion sontdemeurés les mêmes. Le niveau d’activité de la myéloperoxidase(MPO) a significativement augmenté dans les tissus testiculairesdu groupe ayant subi l’ischémie-reperfusion sans traitement subséquent.Cependant, dans le groupe ayant subi l’ischémiereperfusionavec traitement par montélukast, le taux de MPO dansles tissus testiculaires avait significativement diminué. Selon les examensd’histopathologie, dans le groupe 2, de l’oedème, de la congestion,des hémorragies entre les tubules séminifères et une nécrosedes cellules germinales étaient les caractéristiques prédominantesobservées dans les coupes. Par comparaison, la plupart des échantillonsdu groupe 3 (traité par montélukast) présentaient des lésionsde stade I et II. En outre, le score de lésions testiculaires était plusfaible dans le groupe 3 que dans le groupe 2.Conclusion : Les observations actuelles montrent que l’administrationde montélukast diminue la gravité des lésions testiculaires enannulant les effets oxydatifs de l’ischémie-reperfusion des testicules.

scholarly journals Change and significance of the expression of c-kit and SCF following recovery from unilateral testicular torsion in rats

2008 ◽  
Vol 31 (3) ◽  
pp. 98 ◽  
Author(s):  
Yi Guan ◽  
XinMin Zheng ◽  
ZhiWei Yang ◽  
ShiWen Li
Keyword(s):  
Germ Cells ◽  
Testicular Torsion ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Torsion Group ◽  
Treated Group ◽  
Pcr Analysis ◽  
Control Group ◽  
Sham Operation ◽  
Expression Levels

Purpose: To investigate the change in expression levels of c-kit and SCF, and the protective effects of FSH on ischemia-reperfusion injury due to testicular torsion-detorsion. Methods: 24 adult male SD rats were divided into three groups of 8: control group, testicular torsion group and FSH-treated group. The control group was treated with sham-operation. Animals in the testicular torsion and FSH-treated groups were subjected to unilateral 720°counterclockwise testicular torsion for 2 hours and then reperfusion was allowed after detorsion. The FSH-treated group received intraperitoneal injection of FSH 15min before detorsion. Then, the rats were sacrificed and the testes were harvested. Histopathological changes were observed by light microscope, and the expression levels of c-kit, SCF in testicular tissue in the different groups were detected by Immunohistochemical assay and Quantitative Real-time RT-PCR analysis. Finally, the relative proportions of germ cells were measured by FCM. Results: c-kit and SCF were positive expressed in 52.58% and 61.16% of testicular cells of control tissues, respectively. Decreases of c-kit and SCF positive cells (15.01% and 9.18%) were found in the testicular torsion group. After being treated by FSH, the number of positive cells increased (31.25% and 20.01%). Moreover, the c-kit and SCF mRNA expression was increased dramatically (P < 0.01) in response to FSH stimulation. Furthermore, the number of haploid, diploid and tetraploid cells has also increased significantly in drug-treated testes (P < 0.01). Conclusion: The mechanism of tissue damage in the testicular torsion model, includes changes in the expression of c-kit and SCF following torsion. Also, FSH has a protective effect on germ cells after unilateral testicular torsion, which was reflected by increased c-kit and SCF levels.

scholarly journals Melatonin attenuates ovarian ischemia reperfusion injury in rats by decreasing oxidative stress index and peroxynitrite

2020 ◽  
Vol 50 (6) ◽  
pp. 1513-1522
Author(s):  
Şenol KALYONCU ◽  
Bülent YILMAZ ◽  
Mustafa DEMİR ◽  
Meltem TUNCER ◽  
Zehra BOZDAĞ ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Stress Index ◽  
Oxidative Stress Index ◽  
Group 6 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background/aim: To evaluate the protective effect of melatonin on ovarian ischemia reperfusion injury in a rat model. Materials and methods: Forty-eight rats were separated equally into 6 groups. Group 1: sham; Group 2: surgical control with 3-h bilateral ovarian torsion and detorsion; Group 3: intraperitoneal 5% ethanol (1 mL) just after detorsion (as melatonin was dissolved in ethanol); Group 4: 10 mg/kg intraperitoneal melatonin 30 min before 3-h torsion; Group 5:10 mg/kg intraperitoneal melatonin just after detorsion; Group 6:10 mg/kg intraperitoneal melatonin 30 min before torsion and just after detorsion. Both ovaries and blood samples were obtained 7 days after detorsion for histopathological and biochemical analysis.Results: In Group 1, serum levels of total oxidant status (TOS) (μmol H2O2 equivalent/g wet tissue)were significantly lower than in Group2 (P = 0.0023), while tissue TOS levels were lower than in Group 3 (P = 0.0030). Similarly, serum and tissue levels of peroxynitrite in Group 6were significantly lower than those ofGroup 2 (P = 0.0023 and P = 0.040, respectively). Moreover, serum oxidative stress index (OSI) (arbitrary unit) levels were significantly increased in Group 2 when compared to groups 1 and 6 (P = 0.0023 and P= 0.0016, respectively) and in Group 3 with respect to groups 1, 4, 5, and 6 (P = 0.0023, P = 0.0026, P = 0.0008, and P = 0.0011, respectively). Furthermore, there was a significant decrease in histopathological scores including follicular degeneration, vascular congestion, hemorrhage, and inflammation in the melatonin and sham groups in comparison with control groups. Additionally, primordial follicle count was significantly higher in Group 6 than in Group 2 (P = 0.0002).Conclusion: Melatonin attenuates ischemia reperfusion damage in a rat torsion/detorsion model by improving histopathological and biochemical findings including OSI and peroxynitrite.

Abstract 331: Activation of the Safe Pathway Against Cardiac Ischemia-Reperfusion Injury Goes Beyond the Risk Pathway in the Late Pregnancy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jingyuan Li ◽  
Mansoureh Eghbali
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Late Pregnancy ◽  
Treated Group ◽  
Pi3k Inhibitor ◽  
Pi3k Inhibitor Ly294002 ◽  
Risk Pathway ◽  
Group 2 ◽  
Phosphoinositide 3 Kinase

Introduction: We have recently shown that the heart of late pregnant (LP) rodent is more prone to ischemia/reperfusion (I/R) injury compared to non-pregnant. We also reported that post-ischemic adminstartion of (ITLD) protects the LP hearts against I/R injury. Here we investigated Survivor Activating Factor Enhancement (SAFE) pathway, which requires the activation of the signal transducer and activator of transcription 3 (STAT-3) and it can successfully lessen cardiomyocyte death at the time of reperfusion, independently of the activation of the already well-described Reperfusion Injury Salvage Kinase (RISK) pathway (which includes activation of phosphoinositide 3-kinase (PI3K) signaling pathways) in ITLD-induced cardioprotetion. Methods: Isolated LP mouse hearts were subjected to 20 min ischemia followed by 40 reperfusion with 1) Krebs Henseleit buffer (CTRL group), 2) 1% intralipid (ITLD group) or 3) ITLD+STAT3 inhibitor Stattic (20 μM, Stattic group), and 4) ITLD+PI3K inhibitor LY294002 (45 μM). Hemodynamics and myocardial infarction were measured. Two-way and one-way ANOVA was used for statistical analysis. The data are from four to six mice in each group. P<0.05 was considered statistically significant. Values are expressed as mean± SE. Results: The Intralipid-induced cardioprotection was only partially abolished by PI3K inhibitor, LY294002, whereas it was fully abolished when stattic was applied at the end of 40 min reperfusion. The RPP was significantly lower in LY294002 treated group compared to the group treated with Intralipid alone, but still significantly higher than ITLD+Stattic: RPP=8881±1331 mmHg*beats/min in ITLD vs. 5212±1955 mmHg*beats/min in ITLD+LY, p<0.05; 1186±563 mmHg*beats/min in ITLD+Stattic vs. 5212±1955 mmHg*beats/min in ITLD+LY, p<0.05. The infarct size was also larger in LY294002 treated group when compared to Intralipid alone (32.8±3.1% in ITLD+LY vs. 21.7±2.6% in ITLD, p<0.05), but lower than ITLD+Stattic group (32.8±3.1% in ITLD+LY vs 47.9±2.5% ITLD+Stattic, p<0.05). Conclusion: Intralipid protects the heart of late pregnant mice against I/R injury mainly through SAFE-STAT3 pathway.

Hepatic Stellate Cells Play a Functional Role in Exacerbating Ischemia-Reperfusion Injury in Rat Liver

2019 ◽  
Vol 60 (1-2) ◽  
pp. 74-85 ◽  
Author(s):  
Tomokazu Takahashi ◽  
Masato Yoshioka ◽  
Hiroshi Uchinami ◽  
Yasuhiko Nakagawa ◽  
Naohiko Otsuka ◽  
...  
Keyword(s):  
Rat Liver ◽  
Hepatic Stellate Cells ◽  
Functional Role ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Stellate Cells ◽  
Treated Group ◽  
Sprague Dawley ◽  
Perfusion Rate ◽  
Sprague Dawley Rats

Purpose: The involvement of hepatic stellate cells (HSCs) with ischemia-reperfusion (I/R) injury in rat liver was examined using gliotoxin, which is known to induce HSC apoptosis. Methods: Male Sprague-Dawley rats were used. HSC was represented by a glial fibrillary acidic protein (GFAP)-positive cell. Liver ischemia was produced by cross-clamping the hepatoduodenal ligament. The degree of I/R injury was evaluated by a release of aminotransferases. Sinusoidal diameter and sinusoidal perfusion rates were examined using intravital fluorescence microscopy. Results: Gliotoxin significantly decreased the number of GFAP-positive cells 48 h after dosing (2.50 ± 0.19% [mean ± SD] in the nontreated group vs. 1.91 ± 0.46% in the gliotoxin-treated group). Liver damage was significantly suppressed by the pretreatment with gliotoxin. Sinusoidal diameters in zone 3 were wider in the gliotoxin group (10.25 ± 0.35 µm) than in the nontreated group (8.21 ± 0.50 µm). The sinusoidal perfusion rate was maintained as well in the gliotoxin group as in normal livers, even after I/R. Conclusions: Pretreatment with gliotoxin significantly reduced the number of HSCs in the liver and further suppressed liver injury following I/R. It is strongly suggested that HSCs play a functional role in exacerbating the degree of I/R injury of the liver.

scholarly journals Probucol Reduces Testicular Torsion/Detorsion-Induced Ischemia/Reperfusion Injury in Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Si-Ming Wei ◽  
Yu-Min Huang ◽  
Jian Zhou
Keyword(s):  
Reactive Oxygen Species ◽  
Protein Expression ◽  
Testicular Torsion ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Treated Group ◽  
Myeloperoxidase Activity ◽  
Oxygen Species ◽  
Neutrophil Accumulation

This study investigated the effect of probucol, a potent antioxidant, on testicular torsion/detorsion-induced ischemia/reperfusion injury attributable to excess reactive oxygen species released by neutrophils. Sixty male Sprague-Dawley rats were randomly divided into sham-operated control, ischemia-reperfusion, and probucol-treated groups. In the ischemia-reperfusion group, testicular detorsion was performed after 2 hours of left testicular torsion. In the probucol-treated group, after performing the same surgical procedures as in the ischemia-reperfusion group, probucol was given intraperitoneally at testicular detorsion. Orchiectomy was performed to evaluate protein expression of E-selectin which is an endothelial cell adhesion molecule and mediates neutrophil adhesion to vascular endothelium, myeloperoxidase activity (a mark of neutrophil accumulation in the testis), malondialdehyde level (an indicator of reactive oxygen species), and spermatogenesis. E-selectin protein expression, myeloperoxidase activity, and malondialdehyde level were significantly increased, and testicular spermatogenesis was significantly decreased in the ipsilateral testes in the ischemia-reperfusion group, compared with the control group. The probucol-treated group showed significant decreases in E-selectin protein expression, myeloperoxidase activity, and malondialdehyde level and significant increase in testicular spermatogenesis in the ipsilateral testes, compared with the ischemia-reperfusion group. These findings indicate that probucol can protect testicular spermatogenesis by reducing overgeneration of reactive oxygen species by inhibiting E-selectin protein expression and neutrophil accumulation in the testis.

scholarly journals The influence of Theranekron® on glucose-6-phosphate dehydrogenase activity in rat ovaries, intact and with ischemia-reperfusion injury

2021 ◽  
Vol 91 (1) ◽  
pp. 81-88
Author(s):  
Tolunay Kozlu ◽  
◽  
Fatma Güler ◽  
Pınar Peker Akalın ◽  
Filiz Kazak ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Dehydrogenase Activity ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Control Group ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Glucose 6 Phosphate Dehydrogenase

The effect of Theranekron® on rat ovaries was evaluated in healthy and ischemia-reperfusion injury models. The rats were divided into four groups: group 1: control, group 2: Theranekron® (single dose of 0.3 mg/kg intraperitoneally), group 3: torsion + detorsion, and group 4: torsion + detorsion + Theranekron® (single dose 0,3 mg/kg, intraperitoneally). The ovaries were homogenized by sonication before the analysis and supernatant glucose-6-phosphate dehydrogenase activity, reduced nicotinamide adenine dinucleotide phosphate, reduced glutathione and total protein levels were evaluated spectrophotometrically. Ovary tissues were histologically examined. In group 2, glucose-6-phosphate dehydrogenase activity was significantly reduced (P<0.01) compared to the control group and an increased number of atretic follicles, and hyperaemic and haemorrhagic regions were seen histologically; in group 3, although glucose-6-phosphate dehydrogenase activity was not changed, intense hyperaemia and hemorrhage was observed in the veins of the medulla region and in the cortex. Group 4 showed a decrease in glucose-6-phosphate dehydrogenase activity compared to the control group (P<0.01). Histologically, when compared to group 3, group 4 showed fewer atretic follicles and decreased hyperaemia and hemorrhage in the ovaries, excluding the medulla region. There were no significant differences regarding reduced glutathione and reduced nicotinamide adenine dinucleotide phosphate levels between the groups. The Theranekron® dose applied had some negative effects, such as reduced glucose-6-phosphate dehydrogenase activity, an increased number of atretic follicles, and hyperemia in the corpus luteum and medulla region in intact rat ovaries. Although it reduced glucose-6-phosphate dehydrogenase activity, Theranekron® may have had slight remedial effects on rat ovaries with ischemia-reperfusion injury.

scholarly journals Protective Effect of Lycopene against Reperfusion Injury in Rats with Ovarian Torsion: A Biochemical and Histopathological Evaluation

2020 ◽  
Vol 12 (01) ◽  
pp. 32-37
Author(s):  
Emsal Pinar Topdagi Yilmaz ◽  
Harun Un ◽  
Betul Gundogdu ◽  
Elif Polat ◽  
Seda Askin ◽  
...  
Keyword(s):  
Tissue Damage ◽  
Ischemia Reperfusion ◽  
Ovarian Torsion ◽  
Female Rats ◽  
Sham Operation ◽  
Dependent Manner ◽  
Conservative Approach ◽  
Group 4 ◽  
Group 3 ◽  
Group 2

Abstract Objective The aim of our study was to evaluate the effect of two different doses of lycopene, an antioxidant, on experimentally induced ovarian ischemia/reperfusion (IR) injury in rat model. Materials and Methods Twenty-four female rats were randomly divided into four groups: sham operation (group 1), 3-hour ischemia, 3-hour reperfusion (IR) (group 2), and IR + 100 mg/kg lycopene (PO) (group 3), IR + 200 mg/kg of lycopene (group 4). The rats’ superoxide dismutase (SOD), myeloperoxidase (MPO) activities, malondialdehyde (MDA), and glutathione (GSH) levels were calculated. Ovarian tissue damage was assessed using a histopathological scoring system. Results Serum parameter levels and histological scores showed that treatment with lycopene may be conservative approach to prevent IR injury after the ovarian detorsion procedure.The improvement with lycopene was higher at 200 mg than at 100 mg. The MPO and MDA values were significantly lower in groups 3 and 4 as compared with group 2 (p < 0.05), whereas the MPO and MDA values were lower in group 4 as compared with group 3.The SOD and GSH values were significantly higher in groups 3 and 4 as compared with group 2 (p < 0.05), whereas the SOD and GSH values were higher in group 4 as compared with group 3.Tissue damage scores were elevated in the IR group compared with the sham group, but the treatment with different lycopene doses after reperfusion improved the histopathological tissue damage scores. Conclusion The results showed that lycopene treatment reduced ovarian IR damage. Antioxidant activity was found to increase in a dose-dependent manner. Lycopene treatment may be conservative approach for ovarian torsion patients after the detorsion procedure to prevent IR damage.

scholarly journals Electroacupuncture Ameliorates Cerebral Ischemia-Reperfusion Injury by Regulation of Autophagy and Apoptosis

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Shi Shu ◽  
Chun-Ming Li ◽  
Yan-Li You ◽  
Xiao-Lu Qian ◽  
Shuang Zhou ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Cerebral Infarction ◽  
Neurological Deficit ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Beclin 1 ◽  
Male Rats ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Sham Operation Group

Background. The therapeutic mechanisms of cerebral ischemia treatment by acupuncture are yet not well addressed.Objective. We investigated the effects of electroacupuncture (EA) at GV26 observing the expression of autophagy-related proteins Beclin-1 and LC3B and proportion of apoptotic cells and Bcl-2 positive cells in MCAO/R model rats.Methods. Sprague-Dawley (SD) male rats were randomly assigned to 7 groups: model groups (M6h, M24h, and M72h), EA treatment groups (T6h, T24h, and T72h), and sham operation group (S). Neurological deficit and cerebral infarction volume were measured to assess the improvement effect, while the expression of Beclin-1 and LC3B and proportion of Tunel-positive and Bcl-2 positive cells were examined to explore EA effect on autophagy and apoptosis.Results. EA significantly decreased neurological deficit scores and the volume of cerebral infarction. Beclin-1 was significantly decreased in T24h, while LC3B-II/LC3B-I ratio markedly reduced in 6th hour. EA groups markedly reduced the number of Tunel positive cells, especially in T24h. Meanwhile, the number of Bcl-2 positive cells obviously increased after EA treatment, especially in T6h and T24h.Conclusions. The alleviation of inadequate autophagy and apoptosis may be a key mechanism involved in the reflex regulation of EA at GV26 to treat cerebral ischemia.

scholarly journals Attenuating of NF-Κb/VCAM-1 Expression in Middle Cerebral Artery Occlusion (MCAO) Model by Viola Odorata: Protection Against Injury Ischemia- Reperfusion Injury in Rats

2021 ◽  
Author(s):  
Kiana Karimifar ◽  
◽  
Hiva Alipanah ◽  
Ava Soltani Hekmat ◽  
Mohammad Reza Bigdeli ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Treated Group ◽  
Artery Occlusion ◽  
Control Group ◽  
Neuroprotective Effects ◽  
Inflammatory Processes ◽  
Group 5 ◽  
Group 2

Background: The death of neurons and cerebral edema are the main consequences of stroke. However, inflammatory processes play a key role in aggravating cerebral damage following stroke. The aim of this study was to investigate the effects of Viola odorant extract (VOE) on infarct volume (IV), neurologic deficits (ND), and expression of NF-κB and VCAM-1 in the MCAO model. Method: The animals were randomly separated into 5 groups: (1) control group, (2) vehicle-treated group, (3) MCAO group, (4) VOE25 group, (5) VOE50 group, (6) VOE75 group (n=12). VOE (25, 50, and 75 mg/kg) or distilled water were administered daily for 30 days. Two hours after the last gavage, rats were exposed to 60 minutes of MCAO. Twenty-four hours later, the IV, ND, and NF-κB/VCAM-1 expression were evaluated. Results: V. odorata extract (VOE) exhibited excellent neuroprotective effects by reducing infarct volume (mainly in the core and sub-cortex areas), and induced down-regulation of NF-kB and VCAM-1 expression. Conclusion: This finding suggests that V. odorata could also activate intracellular pathways, which ultimately reduces the expression of NF-κB and VCAM-1 and be useful for developing a novel medical herbs for treating cerebral ischemia.

Irisin Protects Brain against Ischemia/Reperfusion Injury through Suppressing TLR4/MyD88 Pathway

2020 ◽  
Vol 49 (4) ◽  
pp. 346-354
Author(s):  
Qian Yu ◽  
Guangyao Li ◽  
Qian Ding ◽  
Lei Tao ◽  
Jiangjing Li ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Neuronal Damage ◽  
Ischemia Reperfusion ◽  
Score Test ◽  
Artery Occlusion ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Mobility Shift ◽  
Protein Levels ◽  
Myd88 Pathway

Background: Inflammatory response exerts an important role in ischemia/reperfusion (I/R) injury. TLR4 and myeloid differentiation factor 88 (MyD88) are key components in inflammation and are involved in the cerebral I/R injury. Irisin is a skeletal muscle-derived myokine produced after exercise, which was found to suppress inflammation. In this study, we investigated whether irisin could protect the brain from I/R injury through the TLR4/MyD88 pathway. Methods: Male Sprague Dawley rats (20 months, 190 ∼ 240 g) were pretreated with irisin at 10, 50, or 100 mg/kg for consecutive 3 days and then subjected to surgery of middle cerebral artery occlusion or sham operation. Infarct size and neuron loss were measured to evaluate brain damage. The mRNA and protein levels of TLR4 and MyD88 were measured by in situ hybridization and immunohistochemistry, respectively. NF-κB activation was assessed by electrophoretic mobility shift assay. Neurological function was evaluated by neurobehavior score test and passive avoidance test. Results: Irisin could reduce neuronal damage and neurofunctional impairment after I/R injury. This effect was mediated by downregulating the TLR4/MyD88 and inhibiting NF-κB activation. Conclusion: Irisin plays a beneficial effect in I/R injury through regulating the TLR4/MyD88 pathway.

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