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1.
Acta Cir Bras ; 35(5): e202000506, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32638845

RESUMO

PURPOSE: To examine effects of resveratrol on renal ischemia/ reperfusion injury (I/R) in a streptozotocin (STZ)-induced diabetic rat model. METHODS: Twenty-four male Sprague Dawley rats were treated with STZ injection for the development of diabetes, and divided into the following groups: Sham group, I/R group and Resveratrol group (n=8). Resveratrol (RSV) was administered at a dose of 10 mg.kg-1.d-1 fourteen days prior to suffering from I/R. Renal function, histology, SOD, MDA, TUNEL assay and expression of TNF-α, IL-1ß, NF-κB-P65, COX-2 and Caspase3, Bcl2 and Bax were analyzed. RESULTS: Administration of RSV significantly reduced the serum levels of renal dysfunction and injury markers, including creatinine, blood urea nitrogen and MDA; in the other hand, it significantly increased the serum levels of SOD. The protective effect of RSV was also reflected on histologic evaluation. RSV reduced the number of apoptotic cells as determined by TUNEL assay. RSV significantly reduced the protein expression of TNF-α, IL-1ß, NF-κB-P65, COX-2 and Caspase3, and Bax. Meanwhile, RSV significantly increased the protein expression of Bcl2. CONCLUSION: RSV attenuated I/R-induced renal injury in diabetic rats through the modulation of oxidative stress and TNF-α-stimulated inflammation.


Assuntos
Antioxidantes , Diabetes Mellitus Experimental , Traumatismo por Reperfusão , Resveratrol , Animais , Antioxidantes/farmacologia , Inflamação , Rim , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/prevenção & controle , Resveratrol/farmacologia , Fator de Necrose Tumoral alfa
2.
J Stroke Cerebrovasc Dis ; 29(8): 104977, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32689608

RESUMO

BACKGROUND: Ischemic stroke is a severe neurological disorder that affected millions of people worldwide. Neuro-inflammation and apoptosis play an essential role in the pathogenesis of neuronal death during ischemic stroke. Alpha-pinene is a bicyclic terpenoid with anti-inflammatory and anti-apoptotic activities. Accordingly, the main purpose of this study was to assess the protective effect of α-pinene in ischemic stroke. MATERIALS AND METHODS: To induce ischemic stroke in male Wistar rats, the middle cerebral artery was occluded for 60 min followed by 24 h reperfusion. Alpha-pinene was injected intraperitoneally at the beginning of reperfusion. A day after reperfusion, the neurological deficits, volume of infarct area, and blood-brain barrier (BBB) permeability were evaluated. The mRNA expression of inflammatory cytokines as well as pro- and anti-apoptotic genes was assessed by using reverse transcription-polymerase chain reaction. The protein levels of inflammatory cytokines were also measured by ELISA method. RESULTS: The results showed that α-pinene (50 and 100 mg/kg) significantly improved sensorimotor function and decreased the volume of infarct area in the brain. The high permeability of BBB was also alleviated by α-pinene (50 and 100 mg/kg) in ischemic areas. Besides, α-pinene (100 mg/kg) attenuated neuro-inflammation through decreasing both the gene and protein expression of TNF-α and IL-1ß in the hippocampus, cortex, and striatum. Besides, α-pinene (100 mg/kg) suppressed apoptosis via downregulation of the pro-apoptotic Bax mRNA expression with a concomitant upregulation of anti-apoptotic Bcl-2 gene expression. CONCLUSIONS: Overall, it was concluded that α-pinene exerts neuroprotective effect during ischemic stroke through attenuating neuroinflammation and inhibition of apoptosis.


Assuntos
Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Monoterpenos Bicíclicos/farmacologia , Encéfalo/efeitos dos fármacos , Citocinas/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Mediadores da Inflamação/metabolismo , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Comportamento Animal/efeitos dos fármacos , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Permeabilidade Capilar/efeitos dos fármacos , Citocinas/genética , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/fisiopatologia , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Transdução de Sinais , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
3.
Am J Chin Med ; 48(5): 1159-1178, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32668973

RESUMO

Hepatic ischemia-reperfusion (IR) injury remains the major cause of liver damage post-liver surgery or transplantation. Diminishing oxidative stress and inflammatory responses is a powerful channel to reduce the rate of morbidity and mortality. Gastrodin (GSTD), a bioactive compound extracted from the traditional Chinese herbal agent with a long history of clinical application in nervous system diseases, is suggested to possess anti-oxidative effects on liver diseases, such as nonalcoholic fatty liver disease. However, the therapeutic potential of GSTD in liver IR injury remains unclear. In this paper, we performed surgery to set up the 70% hepatic IR injury models in mice after a three-day pretreatment of GSTD. We found the administration of GSTD reduced liver damage, which correlated with lower histological Suzuki's score, lower serum alanine transaminase (AST) and alanine transaminase (ALT) levels, less oxidative stress, and cell apoptosis in a dose-responsive manner, as compared to the parallel control. Meanwhile, we observed a great induction of heme oxygenase-1 (HO-1) and an activation of the p38 mitogen-activated protein kinases/nuclear factor erythroid 2-related factor 2 (p38MAPK/Nrf2) pathway in response to the GSTD pretreatment, while the protective effects upon GSTD diminished in mice with HO-1 heterozygous mutation. In addition, GSTD inhibited IR induced toll-like receptor (TLR) 4, but not TLR2 in a HO-1 dependent manner, leading to a down-regulation of cytokines, such as interleukin (IL)-6 and TNF-[Formula: see text]. Collectively, our findings revealed GSTD attenuated liver IR injury via activation of the HO-1 pathway, providing a novel therapeutic strategy to minimize the IR induced oxidative stress in the process of liver transplantation.


Assuntos
Antioxidantes , Álcoois Benzílicos/administração & dosagem , Álcoois Benzílicos/farmacologia , Glucosídeos/administração & dosagem , Glucosídeos/farmacologia , Fígado , Fator 2 Relacionado a NF-E2/metabolismo , Fitoterapia , Traumatismo por Reperfusão/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Medicamentos de Ervas Chinesas , Heme Oxigenase-1/metabolismo , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Cuidados Pré-Operatórios , Receptor 4 Toll-Like/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
4.
Rev. int. androl. (Internet) ; 18(2): 55-62, abr.-jun. 2020. ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-193760

RESUMO

INTRODUCTION AND OBJECTIVES: Testicular ischemia/reperfusion (I/R) injury develops after torsion and following detorsion of the testis. Reactive oxygen species were produced and oxidative damage begins to occur due to I/R process. Nimesulide, which is a specific cyclooxygenase-2 inhibitor drug, have antioxidant, antiinflammatory, analgesics and antipyretic effects. We aimed to investigate biochemically and histopathologically effect of nimesulide on testis I/R injury in rats induced by the testicular torsion-detorsion. MATERIAL AND METHODS: In this study, 24 albino Wistar male rats were divided into four groups (6 rats in each group): ischemia/reperfusion applied+50mg/kg nimesulide administrated (NIM-50), ischemia/reperfusion applied+100mg/kg nimesulide administrated (NIM-100), ischemia/reperfusion applied (IR) and Sham surgery (SS) groups. Nimesulide was administered to NIM-50 and NIM-100 groups at the 50mg/kg and 100mg/kg doses before 2h applied I/R procedures. The IR group were applied only I/R procedures, no drug treatment was applied. Animals were sacrificed under high dose anesthesia and left testes were extracted. Testes were examined biochemically and histopathologically. RESULTS: Total glutathione (tGSH) and cyclooxygenase-1 (COX-1) levels were increased in the NIM-50 and NIM-100 groups compared to IR group. The levels of COX-2, malondialdehyde (MDA), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were lower in the NIM-50 and NIM-100 groups than in the IR group. Some histopathological changes seen in IR group. This findings were decreased in NIM-50 group and prevented in NIM-100 group. CONCLUSION: Nimesulide prevented inflammation and oxidative stress. Our results suggest that nimesulide may be have a protective effect on testicular I/R injury


INTRODUCCIÓN Y OBJETIVOS: La lesión de isquemia y reperfusión testicular (I/R) se desarrolla después de la torsión y la consiguiente detorsión del testículo. Se produjeron especies reactivas de oxígeno y el daño oxidativo comienza a producirse debido al proceso de I/R. La nimesulida, que es un fármaco inhibidor específico de la ciclooxigenasa 2, tiene efectos antioxidantes, antiinflamatorios, analgésicos y antipiréticos. El objetivo fue investigar el efecto bioquímico e histopatológico de la nimesulida sobre la lesión testicular I/R en ratas inducida por la torsión-detorsión testicular. MATERIAL Y MÉTODOS: En este estudio se dividió a 24 ratas albinas Wistar macho en 4 grupos (6 ratas en cada grupo): isquemia y reperfusión aplicada+50mg/kg de nimesulida administrada (NIM-50), isquemia y reperfusión aplicada+100mg/kg de nimesulida administrada (NIM-100), isquemia y reperfusión aplicada (IR) y cirugía simulada (SS). La nimesulida se administró a los grupos NIM-50 y NIM-100 a las dosis de 50 y 100mg/kg, respectivamente, 2h antes de aplicar los procedimientos de I/R. Al grupo IR se aplicó solo procedimientos I/R, no se aplicó tratamiento farmacológico. Los animales se sacrificaron con anestesia a dosis altas y se extrajeron los testículos izquierdos. Los testículos se examinaron bioquímicamente e histopatológicamente. RESULTADOS: Los niveles totales de glutatión (tGSH) y ciclooxigenasa-1 (COX-1) aumentaron en los grupos NIM-50 y NIM-100 en comparación con el grupo IR. Los niveles de COX-2, malondialdehído (MDA), interleucina 1β (IL-1β) y factor de necrosis tumoral-α (TNF-α) fueron menores en los grupos NIM-50 y NIM-100 que en el grupo IR. Se vieron algunos cambios histopatológicos en el grupo IR. Estos hallazgos disminuyeron en el grupo NIM-50 y se evitaron en el grupo NIM-100. CONCLUSIÓN: La nimesulida previno la inflamación y el estrés oxidativo. Nuestros resultados sugieren que la nimesulida puede tener un efecto protector sobre la lesión testicular I/R


Assuntos
Animais , Masculino , Camundongos , Traumatismo por Reperfusão/prevenção & controle , Anti-Inflamatórios não Esteroides/administração & dosagem , Sulfonamidas/administração & dosagem , Ratos Wistar , Modelos Animais de Doenças , Traumatismo por Reperfusão/patologia
5.
Life Sci ; 256: 117982, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32562693

RESUMO

AIMS: This study was designed to evaluate the protective and therapeutic efficacy of platelet-rich plasma (PRP) against testicular degeneration and germ cell apoptosis after induced spermatic cord torsion/detorsion (TD) in rats. MATERIALS: Forty rats were allocated into 5 groups: 1) control, 2) short torsion/detorsion (STD), 3) long torsion detorsion (LTD), 4) protective (PRP/P) and 5) treatment (PRP/T). Testicular ischemia was induced by twisting the right testis 1080° clockwise for 2.5 h. PRP (10 µl) was injected intra-testicular 5 min before (PRP/P) and 3 h after (PRP/T) detorsion. At the end of the experiment, rats were euthanized at 2, 30, 2, and 30 days for groups 2-5 respectively. Nitric oxide, malondialdehyde, catalase, total antioxidant capacity, reduced glutathione, glutathione-S-transferase, interleukin1 beta, tumor necrosis factor, caspase-3, and B-cell lymphoma 2 expressions were assessed in the testes. Moreover, histological examination was performed. KEY FINDINGS: PRP treatment significantly mitigated the torsion-detorsion induced testicular degeneration. Particularly, by improving the state of oxidative stress (NO, P = 0.0001) and antioxidant markers (TAC, GSH, GST, P = 0.0001-0.01) and decreasing the expression of IL-1ß, TNF-α and cas 3 and increase the BCL2 fold changes (P = 0.0001). The protective use of PRP is superior to the therapeutic use of PRP in the restoration of the testicular histoarchitecture following TD. SIGNIFICANCE: This study illustrates the cyto-protective role of PRP against TD induced testicular cell injury that highlight possible application of PRP as a complementary therapy in different testicular degenerative diseases which might attribute to its ability to ameliorate the oxidative stress and inhibit induced apoptosis.


Assuntos
Plasma Rico em Plaquetas/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Torção do Cordão Espermático/metabolismo , Torção do Cordão Espermático/prevenção & controle , Testículo/metabolismo , Animais , Modelos Animais de Doenças , Masculino , Estresse Oxidativo/fisiologia , Ratos , Ratos Wistar , Traumatismo por Reperfusão/patologia , Torção do Cordão Espermático/patologia , Testículo/patologia , Resultado do Tratamento
6.
Life Sci ; 256: 117987, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32569778

RESUMO

AIMS: Ischemic stroke is the leading cause of severe disability and death worldwide. As the pathogenesis of stroke has not been clearly elucidated and the ability of current therapeutic drugs on crossing the blood-brain barrier (BBB) is extremely low, there is no effective strategy to treat stroke. We aim at investigating the specific advantages of using plasma exosomes (Pla-Exo) for targeting ischemic brain and exploring its underlying mechanism in neuroprotection. MAIN METHODS: Pla-Exo was obtained by a gradient ultracentrifugation of fresh plasma. The quantification of penetrated Pla-Exo through BBB was investigated in vitro BBB model, furthermore, the effects of Pla-Exo and exosomal HSP70 on cerebral ischemia/reperfusion injury were evaluated. KEY FINDINGS: Pla-Exo enhanced BBB crossing by specific interaction between Pla-Exo inherited heat shock protein 70 (HSP70) and endothelial Toll-like receptor 4 (TLR4). As expected, Pla-Exo increased HSP70 expression in the ischemic region through the transfer of HSP70, and led to HSP70 mediated suppression of ROS, thus alleviating cerebral ischemia/reperfusion (I/R) injury by attenuating the deterioration of BBB and preventing mitochondria damage. SIGNIFICANCE: These findings indicated that Pla-Exo can provide protection against ischemia-reperfusion injury via the regulation of HSP70 and it should be further studied as a potential candidate for protection against ischemic injury.


Assuntos
Isquemia Encefálica/metabolismo , Exossomos/metabolismo , Proteínas de Choque Térmico HSP70/administração & dosagem , Plasma/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Isquemia Encefálica/prevenção & controle , Endotélio Vascular/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/antagonistas & inibidores , Traumatismo por Reperfusão/prevenção & controle
7.
Updates Surg ; 72(3): 913-915, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32542560

RESUMO

Optimization of donor-recipient matching is a common concept in liver transplantation. In emergency transplant for acute liver failure, outcome is influenced by timing, patient clinical condition, and graft quality. Although factors like advanced donor age have been linked to a poorer outcome, use of suboptimal or marginal grafts can be inevitable in very unstable patients, if no other graft is available. We present a case of a liver transplant performed in an extremely sick patient suffering from HBV-related fulminant hepatitis, in which a compatible graft from a 76-year-old deceased donor became available only after 3 days of waiting time, during which his conditions further deteriorated. Given the suboptimal matching, normothermic machine perfusion was applied to minimize ischemia-reperfusion injury. Use of machine perfusion could find an indication to modulate the risk associated with an unfavorable donor-recipient matching in high-risk cases.


Assuntos
Sobrevivência de Enxerto , Hepatite B/cirurgia , Transplante de Fígado , Fígado/cirurgia , Preservação de Órgãos/métodos , Perfusão/métodos , Traumatismo por Reperfusão/prevenção & controle , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/métodos , Adulto , Humanos , Masculino , Índice de Gravidade de Doença
8.
Acta Cir Bras ; 35(4): e202000402, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32578722

RESUMO

PURPOSE: To investigate the effects of bradykinin on reperfusion injury in an experimental intestinal ischemia reperfusion model. METHODS: We used 32 Wistar-Albino rats. We composed 4 groups each containing 8 rats. Rats in sham group were sacrified at 100 minutes observation after laparotomy. Thirty minutes reperfusion was performed following 50 minutes ischaemia in control group after observing 20 minutes. Ischaemic preconditioning was performed in one group of the study. We performed the other study group pharmacologic preconditioning by infusional administration of 10 µg/kg/minute bradykinin intravenously. We sacrified all of the rats by taking blood samples to evaluate the lactate and lactate dehydrogenase (LDH) after resection of jejunum for detecting tissue myeloperoxidase (MPO) activity. RESULTS: Lactate and LDH levels were significantly higher in control and study groups than the sham group (P<0.001). There is no difference between the study groups statistically. (P>0.05). The results were the same for MPO levels. Although definitive cell damage was determinated in the control group by hystopatological evaluation, the damage in the study groups observed was lower in different levels. However, there was no significant difference between the study groups statistically (P>0.05). CONCLUSION: Either ischeamic preconditioning or pharmacologic preconditioning made by bradykinin reduced the ischemia reperfusion injury at jejunum.


Assuntos
Bradicinina/farmacologia , Modelos Animais de Doenças , Intestino Delgado/irrigação sanguínea , Precondicionamento Isquêmico/métodos , Traumatismo por Reperfusão/prevenção & controle , Vasodilatadores/farmacologia , Animais , Feminino , Laparotomia , Peroxidase/análise , Distribuição Aleatória , Ratos Wistar , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
9.
Medicine (Baltimore) ; 99(18): e19998, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358375

RESUMO

INTRODUCTION: Acute cerebral infarction is a clinically common cerebrovascular disease. Acute cerebral infarction is characterized by sudden onset, dangerous illness, high risk of death, and disability. Computed tomography perfusion imaging can detect abnormal brain tissue perfusion 30 minutes after the onset of cerebral ischemia, providing the earliest and most valuable information for clinical diagnosis and treatment. In recent years, the effect of traditional Chinese medicine on acute cerebral infarction has been remarkable. METHODS/DESIGN: This study plan randomly divided eligible acute cerebral infarction patients into two groups. Patients in the control group will be treated with conventional Western medicine; patients in the intervention group will be treated with traditional Chinese medicine cooperative therapy on the basis of conventional Western medicine. The curative effects will be selected before treatment, 2 weeks after treatment, and 3 months follow-up. The changes in CT imaging evaluation, NIHSS score, and BI index of the two groups of patients will be observed. DISCUSSION: We aim to provide higher evidence-based medical evidence for traditional Chinese medicine treatment of acute cerebral infarction. And clarify the application value of computed tomography perfusion imaging in the diagnosis and efficacy evaluation of acute cerebral infarction. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000030230, Registered on 03 March 2020.


Assuntos
Infarto Cerebral/terapia , Medicina Tradicional Chinesa/métodos , Traumatismo por Reperfusão/prevenção & controle , Doença Aguda , Circulação Cerebrovascular/fisiologia , Método Duplo-Cego , Humanos , Imagem de Perfusão , Tomografia Computadorizada por Raios X
10.
Gene ; 753: 144789, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32442578

RESUMO

BACKGROUND: This study determined the possible anti-inflammatory and antioxidant renal protective effect of genistein, a soy isoflavone, against kidney damage and functional disorders following renal ischemia/reperfusion (I/R) in male rats. MATERIALS AND METHODS: The animals were dedicated to five groups (n = 7 per group): Sham, Sham + Geni (genistein, 15 mg/kg in 1 ml 1% DMSO, i.p.), Sham + DMSO (1 ml 1% DMSO, i.p.), I/R (bilateral renal ischemia for 45 min followed by 24 h reperfusion), I/R + Geni (genistein, 15 mg/kg). 24-h urine samples, blood and tissue samples of the kidney were collected at the end of 24 h reperfusion period. RESULTS: Compared to sham, sham + Geni and sham + DMSO groups, IR injury (IRI) ended in kidney dysfunction (decreased creatinine clearance, and increased fractional excretion of sodium), increased levels of malondialdehyde, decreased activities of antioxidant enzymes (superoxide dismutase, gluthatione peroxidase, and catalase), increased gene expression levels of TLR4 (Toll-like receptor 4) and TNF-α (tumor necrosis factor-alpha), as well as histological damages in kidney tissue. Genistein administration decreased all the changes. Therefore, genistein apparently protects the kidney against IRI by mitigating both oxidative stress and inflammation. The antioxidant and anti-inflammatory properties of genistein probably exert important roles in improving functional disorders and offer renal protection against IRI.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Genisteína/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Lesão Renal Aguda/metabolismo , Animais , Antioxidantes/farmacologia , Catalase/metabolismo , Genisteína/metabolismo , Inflamação/metabolismo , Isquemia/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Superóxido Dismutase/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
11.
Transplantation ; 104(9): 1792-1803, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32371846

RESUMO

Because of the high demand of organs, the usage of marginal grafts has increased. These marginal organs have a higher risk of developing ischemia-reperfusion injury, which can lead to posttransplant complications. Ex situ machine perfusion (MP), compared with the traditional static cold storage, may better protect these organs from ischemia-reperfusion injury. In addition, MP can also act as a platform for dynamic administration of pharmacological agents or gene therapy to further improve transplant outcomes. Numerous therapeutic agents have been studied under both hypothermic (1-8°C) and normothermic settings. Here, we review all the therapeutics used during MP in different organ systems (lung, liver, kidney, heart). The major categories of therapeutic agents include vasodilators, mesenchymal stem cells, antiinflammatory agents, antiinfection agents, siRNA, and defatting agents. Numerous animal and clinical studies have examined MP therapeutic agents, some of which have even led to the successful reconditioning of discarded grafts. More clinical studies, especially randomized controlled trials, will need to be conducted in the future to solidify these promising results and to define the role of MP therapeutic agents in solid organ transplantation.


Assuntos
Preservação de Órgãos/métodos , Transplante de Órgãos/métodos , Perfusão/métodos , Animais , Anti-Inflamatórios/farmacologia , Terapia Genética , Humanos , Traumatismo por Reperfusão/prevenção & controle , Vasodilatadores/farmacologia
12.
Am J Physiol Renal Physiol ; 318(6): F1531-F1538, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32390514

RESUMO

Renal ischemia-reperfusion injury (I/R) usually occurs in renal transplantation and partial nephrectomy, which could lead to acute kidney injury. However, the effective treatment for renal I/R still remains limited. In the present study, we investigated whether inhibition of chromobox 7 (CBX7) could attenuate renal I/R injury in vivo and in vitro as well as the potential mechanisms. Adult male mice were subjected to right renal ischemia and reperfusion for different periods, both with and without the CBX7 inhibitor UNC3866. In addition, human kidney cells (HK-2) were subjected to a hypoxia/reoxygenation (H/R) process for different periods, both with or without the CBX7 inhibitor or siRNA for CBX7. The results showed that expression of CBX7, glucose regulator protein-78 (GRP78), phosphorylated eukaryotic translation initiation factor-2α (p-eIF2α), and C/EBP homologous protein (CHOP) were increased after extension of I/R and H/R periods. Moreover, overexpression of CBX7 could elevate the expression of CBX7, GRP78, p-eIF2α, and CHOP. However, CBX7 inhibition with either UNC3866 or genetic knockdown led to reduced expression of GRP78, p-eIF2α, and CHOP through nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 activation in I/R and H/R injury. Furthermore, ML385, the Nrf2 inhibitor, could elevate endoplasmic reticulum stress levels, abrogating the protective effects of UNC3866 against renal I/R injury. In conclusion, our results demonstrated that CBX7 inhibition alleviated acute kidney injury by preventing endoplasmic reticulum stress via the Nrf2/HO-1 pathway, indicating that CBX7 inhibitor could be a potential therapeutic target for renal I/R injury.


Assuntos
Lesão Renal Aguda/prevenção & controle , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Rim/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Oligopeptídeos/farmacologia , Complexo Repressor Polycomb 1/antagonistas & inibidores , Traumatismo por Reperfusão/prevenção & controle , Lesão Renal Aguda/enzimologia , Lesão Renal Aguda/genética , Lesão Renal Aguda/patologia , Animais , Hipóxia Celular , Linhagem Celular , Heme Oxigenase-1/genética , Humanos , Rim/enzimologia , Rim/patologia , Masculino , Proteínas de Membrana/genética , Camundongos , Fator 2 Relacionado a NF-E2/genética , Complexo Repressor Polycomb 1/genética , Complexo Repressor Polycomb 1/metabolismo , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologia , Transdução de Sinais
13.
Acta Cir Bras ; 35(2): e202000205, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32428061

RESUMO

Purpose To investigate the effects of induction of selective liver hypothermia in a rodent model. Methods Seven male Wistar rats were subjected to 90 minutes of partial 70% liver ischemia and topic liver 26°C hypothermia (H group). Other seven male Wistar rats were subjected to 90 minutes of partial 70% normothermic liver ischemia (N group). Five additional rats underwent a midline incision and section of liver ligaments under normothermic conditions and without any liver ischemia (sham group). All animals were sacrificed 24-h after reperfusion, and livers were sampled for analyses. Pathology sections were scored for sinusoidal congestion, ballooning, hepatocelllular necrosis and the presence of neutrophilic infiltrates. Results At the end of the experiment, liver tissue expressions of TNF-ɑ, IL-1ß, iNOS and TNF-ɑ/IL-10 ratio were significantly reduced in the H group compared to N group, whereas IL-10 and eNOS were significantly increased in H group. Histopathological injury scores revealed a significant decrease in ischemia/reperfusion (I/R) injuries in H group. Conclusion Selective liver hypothermia prevented I/R injury by inhibiting the release of inflammatory cytokines, preserves microcirculation, prevents hepatocellular necrosis and leukocyte infiltration, allowing maintenance of the liver architecture.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Hipotermia Induzida/métodos , Fígado/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Lesão Pulmonar Aguda/patologia , Animais , Temperatura Corporal , Citocinas/metabolismo , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Isquemia/patologia , Fígado/patologia , Masculino , Necrose/patologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Fator de Necrose Tumoral alfa
15.
J Stroke Cerebrovasc Dis ; 29(6): 104801, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32249206

RESUMO

BACKGROUND: Ischemic stroke is the leading cause of disability and death globally. Micro-RNAs (miRNAs) have been reported to play important roles in the development and pathogenesis of the nervous system. However, the exact function and mechanism of miRNAs have not been fully elucidated about brain damage caused by cerebral ischemia/reperfusion (I/R). METHODS: In this study, we explored the neuroprotective effects of miR-219a-5p on brain using an in vitro ischemia model (mouse neuroblastoma N2a cells treated with oxyglucose deprivation and reperfusion), and in vivo cerebral I/R model in mice. Western blot assay and Reverse Transcription-Polymerase Chain Reaction were used to check the expression of molecules involved. Flow cytometry and cholecystokinin were used to examine cell apoptosis, respectively. RESULTS: Our research shows that miR-219a-5p gradually decreases in cerebral I/R models in vivo and in vitro. In vitro I/R, we find that miR-219a-5p mimics provided evidently protection for cerebral I/R damage, as shown by increased cell viability and decreased the release of LDH and cell apoptosis. Mechanically, our findings indicate that miR-219a-5p binds to cAMP specific 3', 5'-cyclic phosphodiesterase 4D (PDE4D) mRNA in the 3'-UTR region, which subsequently leads to a decrease in Pde4d expression in I/R N2a cells. CONCLUSIONS: Our results provide new ideas for the study of the mechanism of cerebral ischemia/reperfusion injury, and lay the foundation for further research on the treatment of brain I/R injury. Upregulation of miR-219a-5p decreases cerebral ischemia/reperfusion injury by targeting Pde4d in vitro.


Assuntos
Apoptose , Encéfalo/enzimologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Infarto da Artéria Cerebral Média/enzimologia , MicroRNAs/metabolismo , Neurônios/enzimologia , Traumatismo por Reperfusão/enzimologia , Regiões 3' não Traduzidas , Animais , Sítios de Ligação , Encéfalo/patologia , Linhagem Celular Tumoral , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/genética , Infarto da Artéria Cerebral Média/patologia , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Neurônios/patologia , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/prevenção & controle , Transdução de Sinais
16.
J Dairy Sci ; 103(6): 4895-4906, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32229112

RESUMO

The objective of this study was to evaluate the protection conferred by lactoferrin, α-lactalbumin, and ß-lactoglobulin in cerebral ischemia reperfusion (I/R) injury. Rat pheochromocytoma (PC12) cells were used to construct an oxygen and glucose deprivation model in vitro, and ICR mice underwent carotid artery "ligation-relaxation" to construct a cerebral I/R injury model in vivo. The levels of toll-like receptor 4 (TLR4) and downstream factors including nuclear factor-κB, tumor necrosis factor-α, and IL-1ß were measured. Metabonomics detection and data mining were conducted to identify the specific metabolic sponsor of the 3 proteins. The results showed that lactoferrin, α-lactalbumin, and ß-lactoglobulin protected neurons from cerebral I/R injury by increasing the level of bopindolol and subsequently inhibiting the TLR4-related pathway to different degrees; ß-lactoglobulin had the strongest activity of the 3 proteins. In summary, this study is the first to investigate and compare the protective effects of lactoferrin, α-lactalbumin, and ß-lactoglobulin in a cerebral stroke model. The results implicate TLR4 as a novel target of the 3 bioactive proteins to prevent cerebral I/R injury.


Assuntos
Lactalbumina/uso terapêutico , Lactoferrina/uso terapêutico , Lactoglobulinas/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Animais , Glucose/metabolismo , Interleucina-1beta/metabolismo , Lactalbumina/metabolismo , Lactoferrina/metabolismo , Lactoglobulinas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Oxigênio/metabolismo , Células PC12 , Ratos , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
17.
Life Sci ; 253: 117705, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32334008

RESUMO

AIMS: Ischemia-reperfusion injury (IRI) is harmful to patients following kidney transplantation. Hypothermic machine perfusion (HMP) can be adopted to preserve grafts and reduce consequential injury. We hypothesized that aldehyde dehydrogenase 2 (ALDH2) partly mitigates kidney IRI via regulating excessive autophagy in HMP. MATERIALS AND METHODS: The rabbits were assigned to 5 groups: Normal, HMP, HMP + Alda-1, HMP + CYA and cold storage (CS). After the rabbit autologous kidney transplantation, renal pathology and function were evaluated by histological analysis, glomerular related proteins (desmin, nephrin), tubular injury factors (NGAL, Ki67), serum creatinine (Cr) and blood urea nitrogen (BUN). Oxidative stress molecular Malondialdehyde (MDA) and superoxide dismutase (SOD2) expression, as well as inflammatory cytokines (TNF-α, IL-6, IL-10) were assessed by immunohistochemistry. The expression of LC3, p62, ALDH2, p-Akt, mTOR, PTEN, p-PTEN, and 4-HNE were measured by immunohistochemistry, RT-PCR, Western blot analysis or ELISA. KEY FINDINGS: HMP was more effective than CS for kidney preservation, with p- ALDH2 expressed in greater quantities in HMP. The results of kidney pathology and function in HMP + Alda-1 were the best. The MDA & SOD2 and the Vyacheslav score were improved in HMP + CYA. ALDH2 reduced 4-HNE-induced oxidative stress, inflammatory infiltration, the expression of LC3, p62 and inhibited autophagy accompanied by activation of p-Akt and mTOR via p-PTEN/PTEN. SIGNIFICANCE: Akt-mTOR autophagy pathway is a novel target for ALDH2 to reduce renal IRI partly by inhibition of 4-HNE in HMP, then protecting the donated kidney received after cardiac death (DCD).


Assuntos
Hipotermia Induzida/métodos , Transplante de Rim/métodos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Serina-Treonina Quinases TOR/metabolismo , Aldeído-Desidrogenase Mitocondrial/metabolismo , Aldeídos/metabolismo , Animais , Autofagia/fisiologia , Creatinina/sangue , Citocinas/metabolismo , Rim/irrigação sanguínea , Rim/patologia , Rim/cirurgia , Masculino , Estresse Oxidativo/fisiologia , Coelhos
18.
Acta Cir Bras ; 35(1): e202000106, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32236320

RESUMO

PURPOSE: To explore the role of all-trans retinoic acid (ATRA) in renal ischemia/reperfusion injury of diabetic rats. METHODS: Sixty adult male rats were randomly divided into 6 groups, including sham group (S group), ischemia-reperfusion group (I/R group), ischemia-reperfusion+ATRA group (A group), diabetic group (D group), diabetic ischemia-reperfusion group (DI/R group), diabetic ischemia-reperfusion +ATRA group (DA group). The levels of creatinine (Cr), cystatin C (Cys-C) and ß2-microglobulin (ß2-MG) were measured. Morphology of renal tissue was observed under light microscope. RESULTS: DJ-1, Nrf2, HO-1 and caspase-3 were detected by western blot. DJ-1, Nrf2, HO-1 and caspase-3 in I/R group, D group and DI/R group was higher than that in S group. Compared with I/R group, Nrf2 and HO-1 in A group was decreased, but caspase-3 was increased. However, Nrf2 in DA group was higher than that in DI/R group, HO-1 and caspase-3 in DA group were lower than that in DI/R group. Compared with group S, Cr, Cys-C and ß2-MG in I/R group, A group, D group, and DI/R group were higher. Whereas the levels of Cr, Cys-C, ß2-MG and renal injury score in DA group were lower than those in DI/R group. CONCLUSION: ATRA has a protective effect on renal ischemia-reperfusion injury in diabetic rats, maybe relating to DJ/Nrf2 pathway.


Assuntos
Diabetes Mellitus Experimental/induzido quimicamente , Rim/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Tretinoína/uso terapêutico , Animais , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Rim/patologia , Masculino , Fator 2 Relacionado a NF-E2/farmacologia , Ratos , Traumatismo por Reperfusão/patologia , Estreptozocina , Tretinoína/farmacologia
19.
Transplant Proc ; 52(3): 1014-1019, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32115238

RESUMO

Renal ischemia-reperfusion injury (RIRI) occurs after several surgical procedures such as kidney transplantation and partial nephrectomy. Isoquercitrin (IQ) exhibited protective effects in cerebral ischemia-reperfusion injury. In the present study, we aimed to evaluate the effects of IQ on the prevention of RIRI. The mouse model of RIRI was induced by 30-minute clamping of the left renal pedicle after excising of the right kidney, followed by 24-hour reperfusion. Thirty mice were randomly divided into the following 3 groups: sham operation, RIRI model group, and IQ pretreatment + RIRI. Serum creatinine and blood urea nitrogen (BUN) were used for evaluating renal function. Kidney cell apoptosis was measured by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Moreover, the pro-inflammatory cytokines (TNF-α, IL-6), the oxidative stress associated factors (malondialdehyde, superoxide dismutase), and the apoptotic factors (Bcl-2, Bax) were assessed. After RIRI, BUN, creatinine, TNF-α, IL-6, malondialdehyde, and Bax were significantly increased, and levels of superoxide dismutase and Bcl-2/Bax ratio and Bcl-2 expression were decreased markedly. As expect, IQ reversed these changes. These data indicate that IQ plays a protective role during RIRI, which may be partially mediated through the actions of antioxidation, anti-inflammation, and antiapoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Inflamação/metabolismo , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Quercetina/análogos & derivados , Traumatismo por Reperfusão/prevenção & controle , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Quercetina/farmacologia
20.
Bratisl Lek Listy ; 121(3): 211-217, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32115979

RESUMO

OBJECTIVES: Betanin and copper sulphate have been previously indicated as beneficial agents for ischemia/reperfusion (I/R) as antioxidant compounds in various models. We investigated whether betanin and copper have any protective effects on the heart and lung against I/R injury in rats. METHODS: Spraque-Dawley rats were assigned in groups: Sham (laparotomy only), control (I/R only), betanin treatment (100 mg/kg of betanin administered intraperitoneally (i.p.) 60 minutes before I/R) and copper sulfate treatment group (0.1 mg/kg/day copper sulfate i.p. for 7 days before I/R). Ischemia was induced by clamping the aorta between the left renal artery and aortic bifurcation for 45 minutes. After 48-hour reperfusion, the rats were sacrificed and heart/lung tissues were harvested. Malondialdehyde (MDA), myeloperoxidase (MPO), interleukin 6 (IL-6) levels were determined. Apoptosis was determined via TUNEL assay. RESULTS: MDA, MPO, IL-6 levels and apoptotic cells were significantly increased in the I/R group. In both treatment groups, MDA and MPO levels were decreased. IL-6 was significantly decreased in response to betanin administration in the heart, but not in the lung; copper had no effect in either area. The numbers of apoptotic cells were significantly decreased in both treatment groups. CONCLUSION: Betanin and copper may have protective effects on I/R injury in the heart and lung in rats (Fig. 6, Ref. 39).


Assuntos
Betacianinas , Cobre , Traumatismo por Reperfusão , Animais , Betacianinas/farmacologia , Cobre/farmacologia , Coração/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Malondialdeído , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/prevenção & controle
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