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1.
Arq Bras Cardiol ; 117(2): 290-297, 2021 08.
Artigo em Inglês, Português | MEDLINE | ID: mdl-34495221

RESUMO

BACKGROUND: Nucleus tractus solitarius (NTS) is a brain area that plays a key role in kidney and cardiovascular regulation via baroreceptors impulses. OBJECTIVES: The aim of this study was to evaluate the effect of naringin (NAR) and trimetazidine (TMZ) alone and their combination on NTS electrical activity and baroreceptor sensitivity (BRS) in renal ischemia- reperfusion (I/R) injury. METHODS: Forty male Sprague-Dawley rats (200- 250 g) were allocated into 5 groups with 8 in each. 1) Sham; 2) I/R; 3) TMZ 5 mg/kg; 4) NAR 100 mg/kg; and 5) TMZ5+ NAR100. The left femoral vein was cannulated to infuse saline solution or drug and the BRS was evaluated. I/R was induced by occlusion of renal pedicles for 45 min, followed by 4 hours of reperfusion. The NTS local electroencephalogram (EEG) was recorded before, during ischemia and throughout the reperfusion. Phenylephrine was injected intravenously to evaluate BRS at the end of reperfusion time. The data were analyzed by two-way repeated measurement ANOVA followed by Tukey's post hoc test. A p-value <0.05 was considered significant. RESULTS: NTS electrical waves did not change during ischemia time, while they significantly decreased during the entire reperfusion time. NTS electrical activity and BRS dramatically reduced in rats with I/R injury; however, administration of NAR, TMZ alone or their combination significantly improved these changes in rats with I/R injury. CONCLUSIONS: The results showed that I/R injury leads to reduced BRS and NTS electrical activity and there may be an association between I/R and decreased BRS. In addition, NAR and TMZ are promising agents to treat I/R complications.


Assuntos
Traumatismo por Reperfusão , Trimetazidina , Animais , Barorreflexo , Flavanonas , Rim , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Núcleo Solitário , Trimetazidina/farmacologia
2.
Acta Cir Bras ; 36(7): e360707, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34495142

RESUMO

PURPOSE: To clarify the best protocol for performing remote ischemic conditioning and to minimize the consequences of ischemia and reperfusion syndrome in brain, the present study aimed to evaluate different time protocols and the relation of the organs and the antioxidant effects of this technique. METHODS: The rat's left femoral artery was clamped with a microvascular clamp in times that ranged from 1 to 5 minutes, according to the corresponding group. After the cycles of remote ischemic conditioning and a reperfusion of 20 minutes, the brain and the left gastrocnemius were collected. The samples were used to measure glutathione peroxidase, glutathione reductase and catalase levels. RESULTS: In the gastrocnemius, the 4-minute protocol increased the catalase concentration compared to the 1-minute protocol, but the latter increased both glutathione peroxidase and glutathione reductase compared to the former. On the other hand, the brain demonstrated higher catalase and glutathione peroxidase in 5-minute group, and the 3-minute group reached higher values of glutathione reductase. CONCLUSIONS: Remote ischemic conditioning increases brain antioxidant capacity in a time-dependent way, while muscle presents higher protection on 1-minute cycles and tends to decrease its defence with longer cycles of intermittent occlusions of the femoral artery.


Assuntos
Antioxidantes , Traumatismo por Reperfusão , Animais , Encéfalo , Glutationa Peroxidase , Isquemia , Ratos , Traumatismo por Reperfusão/prevenção & controle
3.
Braz J Med Biol Res ; 54(11): e9941, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34495252

RESUMO

Acute kidney injury (AKI) is a common complication in seriously ill patients, while renal ischemia-reperfusion (I/R) injury is the most frequent event in this oxidative renal injury. N-acetylcysteine (NAC) is a small molecule containing a thiol group that has antioxidant properties, promoting detoxification and acting directly as a free radical scavenger. In this study, the protective effect of NAC was investigated in short-term (30 min) and long-term (45 min) ischemic AKI. This was achieved via clamping of the renal artery for 30 or 45 min in Wistar rats to induce I/R injury. AKI worsened with a longer period of ischemia (45 compared to 30 min) due to probable irreversible damage. Preconditioning with NAC in short-term ischemia improved renal blood flow and increased creatinine clearance by reducing oxidative metabolites and increasing antioxidant capacity. Otherwise, NAC did not change these parameters in the long-term ischemia. Therefore, this study demonstrated that the period of ischemia determines the severity of the AKI, and NAC presented antioxidant effects in short-term ischemia but not in long-term ischemia, confirming that there is a possible therapeutic window for its renoprotective effect.


Assuntos
Injúria Renal Aguda , Traumatismo por Reperfusão , Acetilcisteína/uso terapêutico , Injúria Renal Aguda/prevenção & controle , Animais , Humanos , Rim , Estresse Oxidativo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/prevenção & controle
4.
Khirurgiia (Mosk) ; (9): 71-76, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34480458

RESUMO

The ischemia-reperfusion syndrome complicates the course of a number of emergency conditions in various fields of clinical medicine, determines the course, prognosis and outcome of the disease. This review examines various aspects of the etiology, pathogenesis, and clinical manifestations of this syndrome. Particular attention is paid to its prevention and treatment. It is indicated that most of the studies devoted to this problem are of an experimental nature. The use of preparations based on succinic acid in the clinic is seen as the most promising direction in solving this issue.


Assuntos
Traumatismo por Reperfusão , Ácido Succínico , Humanos , Isquemia , Reperfusão , Traumatismo por Reperfusão/diagnóstico , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/prevenção & controle
5.
Int J Mol Sci ; 22(16)2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34445250

RESUMO

The combined impact of an increasing demand for liver transplantation and a growing incidence of nonalcoholic liver disease has provided the impetus for the development of innovative strategies to preserve steatotic livers. A natural oxygen carrier, HEMO2life®, which contains M101 that is extracted from a marine invertebrate, has been used for static cold storage (SCS) and has shown superior results in organ preservation. A total of 36 livers were procured from obese Zucker rats and randomly divided into three groups, i.e., control, SCS-24H and SCS-24H + M101 (M101 at 1 g/L), mimicking the gold standard of organ preservation. Ex situ machine perfusion for 2 h was used to evaluate the quality of the livers. Perfusates were sampled for functional assessment, biochemical analysis and subsequent biopsies were performed for assessment of ischemia-reperfusion markers. Transaminases, GDH and lactate levels at the end of reperfusion were significantly lower in the group preserved with M101 (p < 0.05). Protection from reactive oxygen species (low MDA and higher production of NO2-NO3) and less inflammation (HMGB1) were also observed in this group (p < 0.05). Bcl-1 and caspase-3 were higher in the SCS-24H group (p < 0.05) and presented more histological damage than those preserved with HEMO2life®. These data demonstrate, for the first time, that the addition of HEMO2life® to the preservation solution significantly protects steatotic livers during SCS by decreasing reperfusion injury and improving graft function.


Assuntos
Fígado Gorduroso/metabolismo , Hemoglobinas/farmacologia , Fígado/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Animais , Caspase 3/metabolismo , Ciclina D1/metabolismo , Fígado Gorduroso/patologia , Proteína HMGB1/metabolismo , Ácido Láctico/metabolismo , Masculino , Ratos , Ratos Zucker , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Transaminases/metabolismo
6.
Theriogenology ; 173: 241-248, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34399388

RESUMO

Oxidative stress, caused by extreme accumulation of un-scavenged reactive oxygen species, plays an integral role in the Ischemia-Reperfusion (I/R) injury to the testicles following testicular torsion. The current research aimed to examine the protective effects of crocin as a natural antioxidant on testicular I/R injury in rats. Animals were divided randomly into five groups (seven each): (1) sham group, (2) torsion/detorsion (T/D) group, (3) intact group with 100 mg/kg crocin, (4) and (5) T/D groups followed by treatment with two different doses of crocin (50 and 100 mg/kg (IP)). I/R injury was induced by 720° clockwise torsion of the left testicles for 2 h. After 24 h of reperfusion, blood samples and epididymal sperms were collected to measure biochemical (GPx, SOD, and MDA), hormonal (testosterone), and sperm parameters (total sperm recovery, motility, viability, and morphology). Moreover, affected testicles were subjected to histopathology examination. I/R injury caused a significant reduction in sperm characteristics (except for morphology) (P < 0.05), which could not be significantly improved by crocin administration at either dose (P > 0.05). Johnsen's testicular score, mean seminiferous tubular diameter, and germinal epithelial cell thickness were significantly decreased in the T/D group compared to the intact and sham groups. However, crocin could significantly improve the histopathological parameters in both treatment groups compared to the T/D group (P < 0.05). T/D reduced SOD and GPx activity and testosterone level significantly (except for GPx) compared to the sham group (P < 0.05). However, crocin administration could significantly reverse them. Also, crocin reduced the amount of MDA significantly in the high-dose treatment group in comparison to T/D group (P < 0.05). The results of the current study revealed that crocin could be a promising agent to protect against I/R injury following surgical correction of the testicular torsion.


Assuntos
Traumatismo por Reperfusão , Doenças dos Roedores , Torção do Cordão Espermático , Animais , Carotenoides/farmacologia , Masculino , Malondialdeído , Ratos , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/veterinária , Torção do Cordão Espermático/tratamento farmacológico , Torção do Cordão Espermático/veterinária , Testículo
7.
Int J Mol Sci ; 22(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34360532

RESUMO

Stroke is a major cause of death worldwide, leading to serious disability. Post-ischemic injury, especially in the cerebral ischemia-prone hippocampus, is a serious problem, as it contributes to vascular dementia. Many studies have shown that in the hippocampus, ischemia/reperfusion induces neuronal death through oxidative stress and neuronal zinc (Zn2+) dyshomeostasis. Glutathione (GSH) plays an important role in protecting neurons against oxidative stress as a major intracellular antioxidant. In addition, the thiol group of GSH can function as a principal Zn2+ chelator for the maintenance of Zn2+ homeostasis in neurons. These lines of evidence suggest that neuronal GSH levels could be a key factor in post-stroke neuronal survival. In neurons, excitatory amino acid carrier 1 (EAAC1) is involved in the influx of cysteine, and intracellular cysteine is the rate-limiting substrate for the synthesis of GSH. Recently, several studies have indicated that cysteine uptake through EAAC1 suppresses ischemia-induced neuronal death via the promotion of hippocampal GSH synthesis in ischemic animal models. In this article, we aimed to review and describe the role of GSH in hippocampal neuroprotection after ischemia/reperfusion, focusing on EAAC1.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Glutationa/farmacologia , Hipocampo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Homeostase , Humanos , Estresse Oxidativo
8.
J Biol Regul Homeost Agents ; 35(Spec Issue on Internal Medicine n.1)2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34350748

RESUMO

LINC00665 has been reported to participate in several human diseases. However, the role of LINC00665 in cerebral ischemia-reperfusion (CI/R) is still unknown. This study is designed to investigate the role of LINC00665 in rats with CI/R injury. We established middle cerebral artery occlusion/ reperfusion (MCAO/R) rats model in vivo. PC12 cells treated with oxygen-glucose deprivation/reperfusion (OGD/R) were used to establish in vitro I/R model. RT-qPCR assay was adopted to assess the mRNA expression of LINC00665 and miR-744-5p. MTT assay was used to determine cell viability. The protein expression of Bax and Bcl-2 were detected by Western blot assay. The relationship between LINC00665 and miR-744-5p was confirmed by dual luciferase reporter assay and RNA immunoprecipitation (RIP). In this study, we found that LINC00665 was sharply up regulated in MCAO/R rats and PC12 cells treated with I/R. Functionally, LINC00665 knockdown attenuated oxidative damage in PC12 cells treated with I/R. Moreover, LINC00665 knockdown promoted cell viability, while inhibited cell apoptosis in PC12 cells treated with I/R. In addition, miR-744-5p was confirmed to be a target of LINC00665. LINC00665 knockdown was validated to project CI/R injury by sponging miR-744-5p expression.


Assuntos
Isquemia Encefálica , MicroRNAs , Traumatismo por Reperfusão , Animais , Apoptose , Isquemia Encefálica/genética , Infarto da Artéria Cerebral Média/genética , MicroRNAs/genética , Ratos , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/prevenção & controle
9.
Biomed Pharmacother ; 138: 111539, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34311537

RESUMO

OBJECTIVE: Morin (MRN), a known natural flavonol, has demonstrated its shielding aptitude against ischemia/reperfusion (I/Re) lesion in various organs. Nonetheless, its potential influence on hepatic I/Re-induced injury modulation has not been fully elucidated. Consequently, the current study strived to investigate the mechanistic maneuvering of MRN against hepatic I/Re. Furthermore, the effects of MRN on Nrf2, TLR4, and NLRP3 proteins were evaluated via molecular docking studies. METHODS: For fulfilling this aim, Sprague-Dawley rats were allotted into 4 groups; Sham-operated (ShG), hepatic I/Re (30 min/24 h), and 10 days orally pre-treated MRN (50 and 100 mg/kg). KEY FINDINGS: MRN mechanistic maneuver disclosed its ability to safeguard the hepatocytes partially due to antioxidant aptitude through intensifying the expression/content of Nrf2/HO-1 trajectory accompanied by total antioxidant capacity boosting besides MDA lessening. In addition, MRN anti-inflammatory attribute was affirmed by downsizing the expression/content of TLR4/NF-κB trajectory accompanied by a sequent lessening of TNF-α, IL-1ß, IL-6, and ICAM-1 content. Moreover, MRN action entangled NLRP3 inhibitory character with subsequent MPO rebating. Furthermore, MRN anti-apoptotic trait verified by diminishing the pro-apoptotic and the executioner markers; Bax and caspase-3 levels, respectively. On the other hand, MRN administration proved its shielding action by improving the histopathological deterioration and lessening the serum ALT and AST levels. Finally, in silico studies exhibited moderate to promising binding affinities of MRN with the selected proteins ranging from -4.23 to -6.09 kcal mol-1. CONCLUSION: Higher and lower doses of MRN purveyed plausible defensive mechanisms and abated episodes concomitant with hepatic I/Re mischief in part, by modifying oxidative status and inflammation by the impact on Nrf2/HO-1, TLR4/ NF-κB, and NLRP3 pathway.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Flavonoides/farmacologia , Hepatopatias/prevenção & controle , Fígado/efeitos dos fármacos , Simulação de Acoplamento Molecular , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Receptor 4 Toll-Like/metabolismo , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Fígado/metabolismo , Fígado/patologia , Hepatopatias/metabolismo , Hepatopatias/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ligação Proteica , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Transdução de Sinais
10.
Braz J Med Biol Res ; 54(10): e11028, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34287581

RESUMO

Engeletin is a natural derivative of Smilax glabra rhizomilax that exhibits anti-inflammatory activity and suppresses lipid peroxidation. In the present study, we sought to elucidate the mechanistic basis for the neuroprotective and pro-angiogenic activity of engeltin in a human umbilical vein endothelial cells (HUVECs) oxygen-glucose deprivation and reoxygenation (OGD/R) model system and a middle cerebral artery occlusion (MCAO) rat model of cerebral ischemia and reperfusion injury. These analyses revealed that engeletin (10, 20, or 40 mg/kg) was able to reduce the infarct volume, increase cerebral blood flow, improve neurological function, and bolster the expression of vascular endothelial growth factor (VEGF), vasohibin-2 (Vash-2), angiopoietin-1 (Ang-1), phosphorylated human angiopoietin receptor tyrosine kinase 2 (p-Tie2), and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) in MCAO rats. Similarly, engeletin (100, 200, or 400 nM) markedly enhanced the migration, tube formation, and VEGF expression of HUVECs in an OGD/R model system, while the VEGF receptor (R) inhibitor axitinib reversed the observed changes in HUVEC tube formation activity and Vash-2, VEGF, and CD31 expression. These data suggested that engeletin exhibited significant neuroprotective effects against cerebral ischemia and reperfusion injury in rats, and improved cerebrovascular angiogenesis by modulating the VEGF/vasohibin and Ang-1/Tie-2 pathways.


Assuntos
Isquemia Encefálica , Traumatismo por Reperfusão , Angiopoietina-1 , Animais , Isquemia Encefálica/prevenção & controle , Células Endoteliais , Flavonóis , Glicosídeos , Infarto da Artéria Cerebral Média , Ratos , Traumatismo por Reperfusão/prevenção & controle , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular
11.
Int J Mol Sci ; 22(12)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201112

RESUMO

The Semax (Met-Glu-His-Phe-Pro-Gly-Pro) peptide is a synthetic melanocortin derivative that is used in the treatment of ischemic stroke. Previously, studies of the molecular mechanisms underlying the actions of Semax using models of cerebral ischemia in rats showed that the peptide enhanced the transcription of neurotrophins and their receptors and modulated the expression of genes involved in the immune response. A genome-wide RNA-Seq analysis revealed that, in the rat transient middle cerebral artery occlusion (tMCAO) model, Semax suppressed the expression of inflammatory genes and activated the expression of neurotransmitter genes. Here, we aimed to evaluate the effect of Semax in this model via the brain expression profiling of key proteins involved in inflammation and cell death processes (MMP-9, c-Fos, and JNK), as well as neuroprotection and recovery (CREB) in stroke. At 24 h after tMCAO, we observed the upregulation of active CREB in subcortical structures, including the focus of the ischemic damage; downregulation of MMP-9 and c-Fos in the adjacent frontoparietal cortex; and downregulation of active JNK in both tissues under the action of Semax. Moreover, a regulatory network was constructed. In conclusion, the suppression of inflammatory and cell death processes and the activation of recovery may contribute to the neuroprotective action of Semax at both the transcriptome and protein levels.


Assuntos
Hormônio Adrenocorticotrópico/análogos & derivados , Isquemia Encefálica/prevenção & controle , Encéfalo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/farmacologia , Proteoma/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Transcriptoma/efeitos dos fármacos , Hormônio Adrenocorticotrópico/farmacologia , Animais , Encéfalo/metabolismo , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Modelos Animais de Doenças , Masculino , RNA-Seq , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia
12.
Int J Mol Sci ; 22(14)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34299322

RESUMO

Clinical treatments for ischemic stroke are limited. Neural stem cell (NSC) transplantation can be a promising therapy. Clinically, ischemia and subsequent reperfusion lead to extensive neurovascular injury that involves inflammation, disruption of the blood-brain barrier, and brain cell death. NSCs exhibit multiple potentially therapeutic actions against neurovascular injury. Currently, tissue plasminogen activator (tPA) is the only FDA-approved clot-dissolving agent. While tPA's thrombolytic role within the vasculature is beneficial, tPA's non-thrombolytic deleterious effects aggravates neurovascular injury, restricting the treatment time window (time-sensitive) and tPA eligibility. Thus, new strategies are needed to mitigate tPA's detrimental effects and quickly mediate vascular repair after stroke. Up to date, clinical trials focus on the impact of stem cell therapy on neuro-restoration by delivering cells during the chronic stroke stage. Also, NSCs secrete factors that stimulate endogenous repair mechanisms for early-stage ischemic stroke. This review will present an integrated view of the preclinical perspectives of NSC transplantation as a promising treatment for neurovascular injury, with an emphasis on early-stage ischemic stroke. Further, this will highlight the impact of early sub-acute NSC delivery on improving short-term and long-term stroke outcomes.


Assuntos
AVC Isquêmico/terapia , Células-Tronco Neurais/transplante , Transplante de Células-Tronco/métodos , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Isquemia Encefálica/metabolismo , Isquemia Encefálica/terapia , Fibrinolíticos/administração & dosagem , Humanos , AVC Isquêmico/metabolismo , Metaloendopeptidases/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/terapia , Transplante de Células-Tronco/tendências , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/terapia , Ativador de Plasminogênio Tecidual/uso terapêutico
13.
J Stroke Cerebrovasc Dis ; 30(9): 105987, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34273708

RESUMO

OBJECTIVES: The 10-O-(N N-dimethylaminoethyl)-ginkgolide B methane-sulfonate (XQ-1H) is an effective novel drug for the treatment of ischemic cerebrovascular disease derived from Ginkgolide B, a traditional Chinese medicine, has been widely used in the treatment of cardiovascular and cerebrovascular diseases. However, whether XQ-1H exerts neuroprotective effect via regulating neuronal apoptosis and the underlying mechanism remain to be elucidated. MATERIALS AND METHODS: This study was aimed to investigate the neuroprotective effect of XQ-1H in rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) and the oxygen glucose deprivation/reoxygenation (OGD/R) induced neuronal apoptosis on pheochromocytoma (PC-12) cells. RESULTS: The results showed that administration of XQ-1H at different dosage (7.8, 15.6, 31.2 mg/kg) reduced the brain infarct and edema, attenuated the neuro-behavioral dysfunction, and improved cell morphology in brain tissue after MCAO/R in rats. Moreover, incubation with XQ-1H (1 µM, 3 µM, 10 µM, 50 µM, 100 µM) could increase the cell viability, and showed no toxic effect to PC-12 cells. XQ-1H at following 1 µM, 10 µM, 100 µM decreased the lactate dehydrogenase (LDH) activity and suppressed the cell apoptosis in PC-12 cells exposed to OGD/R. In addition, XQ-1H treatment could significantly inhibit caspase-3 activation both in vivo and in vitro, reciprocally modulate the expression of apoptosis related proteins, bcl-2, and bax via activating PI3K/Akt signaling pathway. For mechanism verification, LY294002, the inhibitor of PI3K/Akt pathway was introduced the expressions of bcl-2 and phosphorylated Akt were down-regulated, the expression of bax was up-regulated, indicating that XQ-1H could alleviate the cell apoptosis through activating the PI3K/Akt pathway. CONCLUSIONS: Our findings demonstrated that XQ-1H treatment could provide a neuroprotective effect against ischemic stroke induced by cerebral ischemia/reperfusion injury in vivo and in vitro through regulating neuronal survival and inhibiting apoptosis. The findings of the study confirmed that XQ-1H could be develop as a potential drug for treatment of cerebral ischemic stroke.


Assuntos
Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Ginkgolídeos/farmacologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Lactonas/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Edema Encefálico/metabolismo , Edema Encefálico/patologia , Edema Encefálico/prevenção & controle , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/fisiopatologia , Masculino , Atividade Motora/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Células PC12 , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Transdução de Sinais
14.
Kidney Int ; 100(3): 597-612, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34181969

RESUMO

Acute kidney injury (AKI) carries high morbidity and mortality, and effective treatments are lacking. Preclinical models support involvement of micro-RNAs (miRs) in AKI pathogenesis, although effects on the kidney transcriptome are unclear. We previously showed that injection of cord blood endothelial colony forming cell-derived exosomes, enriched in miR-486-5p, prevented ischemic AKI in mice. To further define this, we studied direct effects of miR-486-5p in mice with kidney ischemia-reperfusion injury. RNA-Seq was used to compare the impact of miR-486-5p and exosomes on the transcriptome of proximal tubules and kidney endothelial cells 24 hours after ischemia-reperfusion. In mice with AKI, injection of miR-486-5p mimic increased its levels in proximal tubules and endothelial cells, and improved plasma creatinine, histological injury, neutrophil infiltration, and apoptosis. Additionally, miR-486-5p inhibited expression of its target phosphatase and tensin homolog, and activated protein kinase B. In proximal tubules, miR-486-5p or exosomes reduced expression of genes associated with ischemic injury and the tumor necrosis factor (TNF) pathway, and altered distinct apoptotic genes. In endothelial cells, genes associated with metabolic processes were altered by miR-486-5p or exosomes, although TNF pathway genes were not affected. Thus, our results suggest that miR-486-5p may have therapeutic potential in AKI.


Assuntos
Injúria Renal Aguda , MicroRNAs , Traumatismo por Reperfusão , Injúria Renal Aguda/genética , Injúria Renal Aguda/prevenção & controle , Animais , Apoptose , Células Endoteliais , Isquemia , Rim , Camundongos , MicroRNAs/genética , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/prevenção & controle , Transcriptoma
15.
Ann Palliat Med ; 10(6): 6726-6735, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34154355

RESUMO

BACKGROUND: At present, liver cancer deaths of China account for about half of the global liver cancer deaths. The most common physiological change in anesthesia surgery for liver cancer is liver ischemia-reperfusion injury (LIRI). METHODS: The Chinese and English medical databases were searched using a combination of the following search terms: "propofol", "liver cancer", "anesthesia surgery", and "ischemia reperfusion injury" in Chinese or English language, respectively. The articles taking patients received propofol intravenous anesthesia surgery for LIRI in the experimental group and patients received intravenous anesthesia with non-propofol drugs for LIRI in the control group were searched. Rev Man 5.3 software was used for meta-analysis. RESULTS: A total of 18 articles were included, and most were considered to have low-risk bias (that is, medium- and high-quality publications). The meta-analysis results indicated that the superoxide dismutase (SOD) levels from the blockage of the hepatic hilum (B-HH) to the 15-minute opening of the hepatic hilum (O-HH) showed a mean deviation (MD) of -0.33 nU/mL and 95% confidential interval (CI) of -1.81 to 1.15 nmol/L (P<0.05). The levels of malondialdehyde (MDA) from B-HH to O-HH showed a MD of 1.80 nmol/L and 95% CI of 1.53 to 2.07 nmol/l (P<0.05). The MD of alanine transaminase (ALT) levels from B-HH to O-HH was 8.24 IU/L with 95% CI 6.43 to 10.06 IU/L (P<0.05). The MD of aspartate transaminase (AST) levels from B-HH to O-HH was -11.73 IU/L with 95% CI -14.04 to -9.43 IU/L (P<0.05). The RevMan5.3 software was used to draw the funnel chart for each indicator from B-HH to OHH. The results revealed that the circles in some articles were concentrated on the midline and were basically symmetrical with the midline, indicating that the research accuracy was high and there was no bias in publication. DISCUSSION: This meta-analysis confirmed that propofol exerted a protective effect on LIRI during anesthesia surgery with hepatic hilar blockade.


Assuntos
Anestesia , Carcinoma Hepatocelular , Neoplasias Hepáticas , Propofol , Traumatismo por Reperfusão , Carcinoma Hepatocelular/cirurgia , China , Humanos , Fígado , Neoplasias Hepáticas/cirurgia , Propofol/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle
16.
Andrologia ; 53(8): e14117, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34081348

RESUMO

This study aimed to investigate the protective effect of sinapic acid (SA) on biochemical and histopathological changes in an experimental testicular torsion-detorsion rat model. Twenty-four rats were randomised into four groups: sham group, ischemia/reperfusion (IR) group subjected to testicular torsion for 2 hr and then detorsion for 4 hr, and two groups treated with SA1 and SA2 (10 mg/kg and 20 mg/kg, by single intraperitoneal injection, 30 min before reperfusion). Serum testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured by an autoanalyzer, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), protein carbonyl (PC), and nitric oxide (NO) oxidative stress parameters by spectrophotometric methods, and tumour necrosis factor (TNF-α), interleukin-1 beta (IL-1ß), and interleukin 6 (IL-6) parameters by the Elisa method. In addition, immunohistochemical and histopathological examinations were performed on testicular tissues. There was no significant difference between the groups in terms of serum testosterone, FSH and LH levels (p > .05). SA significantly reduced increased testicular damage, oxidative stress, inflammation, cell death and also restored decreased antioxidant enzyme activities (p < .05). Pre-treatment of rats with SA reduced testicular dysfunction and morphological changes IRI. SA's antioxidant, anti-inflammatory, and antiapoptotic properties were found to be protective against testicular IR.


Assuntos
Traumatismo por Reperfusão , Torção do Cordão Espermático , Animais , Ácidos Cumáricos/farmacologia , Ácidos Cumáricos/uso terapêutico , Humanos , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Torção do Cordão Espermático/complicações , Torção do Cordão Espermático/tratamento farmacológico , Torção do Cordão Espermático/metabolismo , Testículo/metabolismo
17.
Andrologia ; 53(8): e14128, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34091938

RESUMO

This experimental study aims to evaluate the efficacy of milrinone against ischaemia-reperfusion injury due to testicular torsion/detorsion. Group 1 was defined as the control group. Testicular torsion/detorsion model was performed in Group 2. Group 3 had similar procedures to the rats in Group 2. In addition, 0.5 mg/kg of milrinone was administered intraperitoneally immediately after testicular torsion in Group 3. Histopathological examinations indicated a dramatic improvement in terms of inflammation, haemorrhage, oedema, congestion, Cosentino and Johnson scores in Group 3 compared to Group 2 (p = .037, p = .045, p = .018, p = .040, p = .033 and p = .03 respectively). Blood biochemical analyses, superoxide dismutase (SOD), glutathione peroxidase (GSH-px) activity and total antioxidant status (TAS) levels increased significantly in Group 3 compared to Group 2 (p = .001, p = .024 and p < .001). Malondialdehyde (MDA), protein carbonyl (PC), interleukin 1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and total oxidant status (TOS) levels decreased in Group 3 compared to Group 2 (p = .001, p = .018, p < .001, p = .036 and p = .002 respectively). Tissue biochemical analyses determined an increase in SOD and GSH-px activity in Group 3 compared to Group 2, while PC and MDA levels were reduced (p = .001, p < .001, p = .038 and p < .001 respectively). Milrinone attenuates ischaemia-reperfusion injury that causes highly harmful effects due to testicular torsion/detorsion.


Assuntos
Traumatismo por Reperfusão , Torção do Cordão Espermático , Animais , Humanos , Masculino , Malondialdeído , Milrinona , Ratos , Ratos Wistar , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Torção do Cordão Espermático/complicações , Torção do Cordão Espermático/tratamento farmacológico , Testículo
18.
Andrologia ; 53(8): e14143, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34115392

RESUMO

This study was designed to investigate the effects of separate and combined administration of hypothermia and pentoxifylline to preserve the effects on the testicles in an experimental model of testicular torsion/ detorsion injuries in rats. Forty male adult Wistar rats were randomly divided into five groups, control, torsion/detorsion (TD), torsion/detorsion/hypothermia (TD+ICE), torsion/detorsion received of pentoxifylline (40mg/kg, ip) (TD+PTX) and torsion/detorsion/hypothermia/PTX (TD+ICE+PTX). Left testicular torsion (TT) was performed for 4 and half hours, and ice fragments have been used at the beginning of torsion. After the reperfusion period (a week), oxidative maker's serum levels, testosterone hormone, sperm parameters, and histopathological and gene expression evaluations have been performed. Significant adverse changes were observed in the TD group for histological variables, sperm count, oxidative marker, testosterone hormone, Bax, BCL2 and caspase-3 expression. The parameters studied in the group receiving PTX improved in comparison with the TD group, while macroscopical parameters of both the hypothermia and PTX+ICE groups were not different compared with the TD group. The results revealed that PTX, as an antioxidant component, was protective against testicular torsion, while hypothermia and hypothermia plus PTX did not exhibit this property, which may have been due to the duration of hypothermia (4 hr) or reperfusion period.


Assuntos
Hipotermia , Pentoxifilina , Traumatismo por Reperfusão , Torção do Cordão Espermático , Animais , Feminino , Humanos , Hipotermia/metabolismo , Masculino , Malondialdeído/metabolismo , Torção Ovariana , Estresse Oxidativo , Pentoxifilina/uso terapêutico , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Torção do Cordão Espermático/metabolismo , Torção do Cordão Espermático/terapia , Testículo/metabolismo
19.
Int J Mol Sci ; 22(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068301

RESUMO

Maintaining organ viability between donation and transplantation is of critical importance for optimal graft function and survival. To date in pancreas transplantation, static cold storage (SCS) is the most widely practiced method of organ preservation. The first experiments in ex vivo perfusion of the pancreas were performed at the beginning of the 20th century. These perfusions led to organ oedema, hemorrhage, and venous congestion after revascularization. Despite these early hurdles, a number of factors now favor the use of perfusion during preservation: the encouraging results of HMP in kidney transplantation, the development of new perfusion solutions, and the development of organ perfusion machines for the lung, heart, kidneys and liver. This has led to a resurgence of research in machine perfusion for whole organ pancreas preservation. This review highlights the ischemia-reperfusion injuries assessment during ex vivo pancreas perfusion, both for assessment in pre-clinical experimental models as well for future use in the clinic. We evaluated perfusion dynamics, oedema assessment, especially by impedance analysis and MRI, whole organ oxygen consumption, tissue oxygen tension, metabolite concentrations in tissue and perfusate, mitochondrial respiration, cell death, especially by histology, total cell free DNA, caspase activation, and exocrine and endocrine assessment.


Assuntos
Preservação de Órgãos/métodos , Transplante de Pâncreas , Pâncreas/fisiologia , Traumatismo por Reperfusão/prevenção & controle , Sobrevivência de Tecidos , Animais , Humanos
20.
Clinics (Sao Paulo) ; 76: e2513, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33978073

RESUMO

OBJECTIVES: The current study compared the impact of pretreatment with melatonin and N-acetylcysteine (NAC) on the prevention of rat lung damage following intestinal ischemia-reperfusion (iIR). METHODS: Twenty-eight Wistar rats were subjected to intestinal ischemia induced by a 60 min occlusion of the superior mesenteric artery, followed by reperfusion for 120 min. Animals were divided into the following groups (n=7 per group): sham, only abdominal incision; SS+iIR, pretreated with saline solution and iIR; NAC+iIR, pretreated with NAC (20 mg/kg) and iIR; MEL+iIR, pretreated with melatonin (20 mg/kg) and iIR. Oxidative stress and inflammatory mediators were measured and histological analyses were performed in the lung tissues. RESULTS: Data showed a reduction in malondialdehyde (MDA), myeloperoxidase (MPO), and TNF-alpha in the animals pretreated with NAC or MEL when compared to those treated with SS+iIR (p<0.05). An increase in superoxide dismutase (SOD) levels in the NAC- and MEL-pretreated animals as compared to the SS+iIR group (34±8 U/g of tissue; p<0.05) was also observed. TNF-α levels were lower in the MEL+iIR group (91±5 pg/mL) than in the NAC+iIR group (101±6 pg/mL). Histological analysis demonstrated a higher lung lesion score in the SS+iIR group than in the pretreated groups. CONCLUSION: Both agents individually provided tissue protective effect against intestinal IR-induced lung injury, but melatonin was more effective in ameliorating the parameters analyzed in this study.


Assuntos
Lesão Pulmonar Aguda , Melatonina , Traumatismo por Reperfusão , Acetilcisteína/uso terapêutico , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/prevenção & controle , Animais , Isquemia , Melatonina/uso terapêutico , Ratos , Ratos Wistar , Reperfusão , Traumatismo por Reperfusão/prevenção & controle
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