RESUMEN
Liver ischaemia-reperfusion (IR) during hepatic surgeries can lead to liver cell death via oxidative stress and the activation of immune cells, the release of cytokines, and damage-associated molecular patterns. Ascorbic acid has been shown to confer potential protective effects against IR injury, mainly due to its antioxidant properties. This study evaluated the effect of ascorbic acid infusion at different time points during hepatic IR in rats. Thirty-six male Wistar rats were divided into control and experimental groups that received the same total ascorbic acid dose at three different infusion times: before ischaemia, before reperfusion, or before both ischaemia and reperfusion. All of the animals experienced hepatic IR injury. We measured the hepatic enzymes, cytokines, and portal blood flow. Animals receiving ascorbic acid before both ischaemia and reperfusion had lower liver enzyme levels, reduced inflammation, and better portal venous flow than other animals. Divided doses of ascorbic acid before IR may be beneficial for reducing liver injury associated with IR.
Asunto(s)
Ácido Ascórbico , Hígado , Ratas Wistar , Daño por Reperfusión , Animales , Ácido Ascórbico/farmacología , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Masculino , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Ratas , Antioxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos , Citocinas/metabolismo , Vena Porta , Modelos Animales de EnfermedadRESUMEN
PURPOSE: To evaluate the neuroprotective effect of resveratrol, urapidil, and a combined administration of these drugs against middle cerebral artery occlusion (MCAO) induced ischemia/reperfusion (IR) injury model in rats. METHODS: Thirty-five rats were divided into five groups of seven animals each. Animals in IR, IR resveratrol (IRr), IR urapidil (IRu), and IR + combination of resveratrol and urapidil (IRc) were exposed to MCAO induced cerebral ischemia reperfusion injury model. Rats in IRr and IRu groups received 30-mg/kg resveratrol and 5-mg/kg urapidil respectively. Animals in IRc received a combined treatment of both drugs. At the end of the study, brain tissues were used for oxidative stress (malondialdehyde, glutathione, and superoxide dismutase), pro-apoptotic caspase-3, anti-apoptotic Bcl-2, and pro-inflammatory tumor necrosis factor-α cytokine level measurements. RESULTS: The MCAO model successfully replicated IR injury with significant histopathological changes, elevated tissue oxidative stress, and upregulated apoptotic and inflammatory protein expression in IR group compared to control group (p < 0.001). All parameters were significantly alleviated in IRr group compared to IR group (all p < 0.05). In IRu group, all parameters except for caspase-3 and Bcl-2 were also significantly different than IR group (all p < 0.05). The IRc group showed the biggest difference compared to IR group in all parameters (all p < 0.001). The IRc had higher superoxide dismutase and Bcl-2 levels, and lower caspase-3 levels compared to both IRr and IRu groups (all p < 0.05). Also, the IRc group had lower MDA and TNF-α levels compared to IRu group (all p < 0.05). CONCLUSIONS: The results indicate that combined treatment of resveratrol and urapidil may be a novel strategy to downregulate neurodegeneration in cerebral IR injury.
Asunto(s)
Modelos Animales de Enfermedad , Fármacos Neuroprotectores , Estrés Oxidativo , Daño por Reperfusión , Resveratrol , Estilbenos , Animales , Resveratrol/farmacología , Resveratrol/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/farmacología , Masculino , Estrés Oxidativo/efectos de los fármacos , Estilbenos/uso terapéutico , Estilbenos/farmacología , Quimioterapia Combinada , Ratas Wistar , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Resultado del Tratamiento , Ratas , Factor de Necrosis Tumoral alfa/análisis , Superóxido Dismutasa/análisis , Superóxido Dismutasa/metabolismo , Malondialdehído/análisis , Malondialdehído/metabolismo , Reproducibilidad de los Resultados , Apoptosis/efectos de los fármacos , Distribución Aleatoria , Isquemia Encefálica/tratamiento farmacológico , Antioxidantes/uso terapéutico , Antioxidantes/farmacología , Caspasa 3/metabolismo , Caspasa 3/análisisRESUMEN
BACKGROUND: Despite the well-recognized effectiveness of Ruscus aculetus extract combined or not with ascorbic acid (AA) and hesperidine methyl chalcone (HMC) on ischemia reperfusion (I/R) injury protection, little is known about the contribution of each constituent for this effect. OBJECTIVE: To investigate the effects of AA and HMC combined or not with Ruscus extract on increased macromolecular permeability and leukocyte-endothelium interaction induced by I/R injury. METHODS: Hamsters were treated daily during two weeks with filtered water (placebo), AA (33, 100 and 300âmg/kg/day) and HMC (50, 150 and 450âmg/kg/day) combined or not with Ruscus extract (50, 150 and 450âmg/kg/day). On the day of experiment, the cheek pouch microcirculation underwent 30âmin of ischemia, and the number of rolling and adherent leukocytes and leaky sites were evaluated before ischemia and during 45âmin of reperfusion. RESULTS: Ruscus extract combined with AA and HMC (Ruscus extract mixture) significantly prevented post-ischemic increase in leukocyte rolling and adhesion and macromolecular permeability compared to placebo and these effects were more prominent than AA and HMC alone on leukocyte adhesion and macromolecular leakage. CONCLUSION: Ruscus extract mixture were more effective than its isolated constituents in protect the hamster cheek pouch microcirculation against I/R injury.
Asunto(s)
Ácido Ascórbico , Leucocitos , Extractos Vegetales , Daño por Reperfusión , Animales , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Daño por Reperfusión/metabolismo , Ácido Ascórbico/farmacología , Ácido Ascórbico/uso terapéutico , Leucocitos/efectos de los fármacos , Leucocitos/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Cricetinae , Masculino , Chalconas/farmacología , Chalconas/uso terapéutico , Mesocricetus , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Permeabilidad Capilar/efectos de los fármacos , Adhesión Celular/efectos de los fármacos , Hesperidina/análogos & derivadosRESUMEN
OBJECTIVE: Blood-brain barrier is a protective layer that regulates the influx and efflux of biological materials for cerebral tissue. The aim of this study was to investigate the effects of Biochanin A on cerebral histopathology and blood-brain barrier immunohistochemically. METHODS: A total of 24 rats were assigned to three groups: sham, ischemia-reperfusion, and ischemia-reperfusion+Biochanin A. Ischemia-reperfusion was performed by occluding the left carotid artery for 2/24 h. Notably, 20 mg/kg Biochanin A was administered to rats for 7 days after ischemia-reperfusion. Blood was collected for malondialdehyde and total oxidant/antioxidant status analysis. Cerebral tissues were processed for histopathology and further for immunohistochemical analysis. RESULTS: Malondialdehyde content with total oxidant status value was significantly increased and total antioxidant status values were significantly decreased in the ischemia-reperfusion group compared with the sham group. Biochanin A treatment significantly improved scores in the ischemia-reperfusion+Biochanin A group. The normal histological appearance was recorded in the cerebral sections of the sham group. Degenerated neurons and vascular structures with disrupted integrity of the cerebral cortex were observed after ischemia-reperfusion. Biochanin A alleviated the histopathology in the cerebrum in the ischemia-reperfusion+Biochanin A group. Ischemia-reperfusion injury decreased the expression of blood-brain barrier in the ischemia-reperfusion group compared to the sham group. Administration of Biochanin A upregulated the blood-brain barrier immunoreactivity in the cerebrum by restoring blood-brain barrier. CONCLUSION: Cerebral ischemia-reperfusion caused an increase in oxidative stress and pathological lesions in the cerebrum. Biochanin A treatment restored the adverse effects of ischemia-reperfusion injury by restoring blood-brain barrier.
Asunto(s)
Barrera Hematoencefálica , Genisteína , Malondialdehído , Daño por Reperfusión , Animales , Genisteína/farmacología , Genisteína/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Barrera Hematoencefálica/efectos de los fármacos , Masculino , Malondialdehído/análisis , Ratas , Isquemia Encefálica/tratamiento farmacológico , Ratas Wistar , Antioxidantes/farmacología , Inmunohistoquímica , Estrés Oxidativo/efectos de los fármacos , Modelos Animales de EnfermedadRESUMEN
Acute kidney injury (AKI) often triggers physiological processes aimed at restoring renal function and architecture. However, this response can become maladaptive, leading to nephron loss and fibrosis. Although the therapeutic effects of resveratrol (RSV) are well established, its impact after AKI and for subsequent chronic kidney disease (CKD) remains unclear. This study assessed whether transient administration of RSV following ischaemia-reperfusion injury (IRI) could prevent the progression to CKD. Forty-one male Wistar rats were assigned randomly to sham surgery, bilateral renal ischaemia for 30 min (IR) or IR+RSV. The RSV treatment commenced 24 h after IRI and continued for 10 days. The rats were studied for either 10 days or 5 months, after which kidney function and structure were evaluated. Mitochondrial homeostasis, oxidant defence and renal inflammation state were also evaluated. Despite having the same severity of AKI, rats receiving RSV for 10 days after IRI exhibited significant improvement in kidney histological injury and reduced inflammation, although renal haemodynamic recovery was less pronounced. Resveratrol effectively prevented the elevation of tubular injury-related molecules and profibrotic signalling with reduced myofibroblast proliferation. Furthermore, RSV substantially improved the antioxidant response and mitochondrial homeostasis. After 5 months, RSV prevented the transition to CKD, as evidenced by the prevention of progressive proteinuria, renal dysfunction and tubulointerstitial fibrosis. This study demonstrates that a brief treatment with RSV following IRI is enough to prevent maladaptive repair and the development of CKD. Our findings highlight the importance of the early days of reperfusion, indicating that maladaptive responses can be reduced effectively following severe AKI. KEY POINTS: Physiological processes activated after acute kidney injury (AKI) can lead to maladaptive responses, causing nephron loss and fibrosis. Prophylactic renoprotection with resveratrol (RSV) has been described in experimental AKI, but its impact after AKI and for subsequent chronic kidney disease (CKD) remains unclear. In this study, we found that histological tubular injury persists 10 days after ischaemia-reperfusion injury and contributes to a failed repair phenotype in proximal tubular cells. Short-term RSV intervention influenced the post-ischaemic repair response and accelerated tubular recovery by reducing oxidative stress and mitochondrial damage. Furthermore, RSV targeted inflammation and profibrotic signalling during the maladaptive response, normalizing both processes. Resveratrol effectively prevented AKI-to-CKD transition even 5 months after the intervention. The study serves as a proof of concept, proposing RSV as a valuable candidate for further translational clinical studies to mitigate AKI-to-CKD transition.
Asunto(s)
Lesión Renal Aguda , Insuficiencia Renal Crónica , Daño por Reperfusión , Ratas , Masculino , Animales , Resveratrol/farmacología , Resveratrol/uso terapéutico , Ratas Wistar , Riñón/patología , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/etiología , Insuficiencia Renal Crónica/patología , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/prevención & control , Lesión Renal Aguda/patología , Inflamación/complicaciones , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Daño por Reperfusión/complicaciones , FibrosisRESUMEN
PURPOSE: Cerebral ischemia-reperfusion (I/R) is a neurovascular disorder that leads to brain injury. In mice, Fasudil improves nerve injury induced by I/R. However, it is unclear if this is mediated by increased peroxisome proliferator-activated receptor-α (PPARα) expression and reduced oxidative damage. This study aimed to investigate the neuroprotective mechanism of action of Fasudil. METHODS: MCAO (Middle cerebral artery occlusion) was performed in male C57BL/6J wild-type and PPARα KO mice between September 2021 to April 2023. Mice were treated with Fasudil and saline; 2,3,5-Triphenyltetrazolium chloride (TTC) staining was performed to analyze cerebral infarction. PPARα and Rho-associated protein kinase (ROCK) expression were detected using Western blot, and the expression of NADPH subunit Nox2 mRNA was detected using real-time polymerase chain reaction. The NADPH oxidase activity level and reactive oxygen species (ROS) content were also investigated. RESULTS: After cerebral ischemia, the volume of cerebral necrosis was reduced in wild-type mice treated with Fasudil. The expression of PPARα was increased, while ROCK was decreased. Nox2 mRNA expression, NADPH oxidase activity, and ROS content decreased. There were no significant changes in cerebral necrosis volumes, NADPH oxidase activity, and ROS content in the PPARα KO mice treated with Fasudil. CONCLUSIONS: In mice, the neuroprotective effect of Fasudil depends on the expression of PPARα induced by ROCK-PPARα-NOX axis-mediated reduction in ROS and associated oxidative damage.
Asunto(s)
Isquemia Encefálica , Daño por Reperfusión , Ratones , Masculino , Animales , PPAR alfa/fisiología , Especies Reactivas de Oxígeno/metabolismo , Neuroprotección , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Daño por Reperfusión/genética , Ratones Endogámicos C57BL , Isquemia , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/prevención & control , NADPH Oxidasas/genética , NADPH Oxidasas/metabolismo , Reperfusión , Necrosis , ARN MensajeroRESUMEN
PURPOSE: To investigate the role of puerarin on renal fibrosis and the underlying mechanism in renal ischemia and reperfusion (I/R) model. METHODS: Rats were intraperitoneally injected with puerarin (50 or 100 mg/kg) per day for one week before renal I/R. The level of renal collagen deposition and interstitial fibrosis were observed by hematoxylin and eosin and Sirius Red staining, and the expression of α-smooth muscle actin (α-SMA) was examined by immunohistochemical staining. The ferroptosis related factors and TLR4/Nox4-pathway-associated proteins were detected by Western blotting. RESULTS: Puerarin was observed to alleviate renal collagen deposition, interstitial fibrosis and the α-SMA expression induced by I/R. Superoxide dismutase (SOD) activities and glutathione (GSH) level were decreased in I/R and hypoxia/reoxygenation (H/R), whereas malondialdehyde (MDA) and Fe2+ level increased. However, puerarin reversed SOD, MDA, GSH and Fe2+ level changes induced by I/R and H/R. Besides, Western blot indicated that puerarin inhibited the expression of ferroptosis related factors in a dose-dependent manner, which further demonstrated that puerarin had the effect to attenuate ferroptosis. Moreover, the increased expression of TLR/Nox4-pathway-associated proteins were observed in I/R and H/R group, but puerarin alleviated the elevated TLR/Nox4 expression. CONCLUSIONS: Our results suggested that puerarin inhibited oxidative stress and ferroptosis induced by I/R and, thus, delayed the progression of renal fibrosis, providing a new target for the treatment of renal fibrosis.
Asunto(s)
Ferroptosis , Enfermedades Renales , Daño por Reperfusión , Ratas , Animales , Receptor Toll-Like 4/metabolismo , Estrés Oxidativo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Daño por Reperfusión/metabolismo , Isquemia , Fibrosis , Superóxido Dismutasa/metabolismo , NADPH Oxidasa 4/metabolismoRESUMEN
PURPOSE: To explore the protection of naringenin against oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT22 cell injury, a cell model of cerebral ischemia/reperfusion (I/R) injury in vitro, focusing on SIRT1/FOXO1 signaling pathway. METHODS: Cytotoxicity, apoptosis, reactive oxygen species (ROS) generation, malondialdehyde (MDA) content, 4-hydroxynonenoic acid (4-HNE) level, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were measured by commercial kits. Inflammatory cytokines levels were determined by enzyme-linked immunosorbent assay (ELISA). The protein expressions were monitored by Western blot analysis. RESULTS: Naringenin significantly ameliorated OGD/R-induced cytotoxicity and apoptosis in HT22 cells. Meanwhile, naringenin promoted SIRT1 and FOXO1 protein expressions in OGD/R-subjected HT22 cells. In addition, naringenin attenuated OGD/R-induced cytotoxicity, apoptosis, oxidative stress (the increased ROS, MDA and 4-HNE levels, and the decreased SOD, GSH-Px and CAT activities) and inflammatory response (the increased tumor necrosis factor-α, interleukin [IL]-1ß, and IL-6 levels and the decreased IL-10 level), which were blocked by the inhibition of the SIRT1/FOXO1 signaling pathway induced by SIRT1-siRNA transfection. CONCLUSIONS: Naringenin protected HT22 cells against OGD/R injury depending on its antioxidant and anti-inflammatory activities via promoting the SIRT1/FOXO1 signaling pathway.
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Isquemia Encefálica , Daño por Reperfusión , Humanos , Antioxidantes/metabolismo , Apoptosis , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/prevención & control , Proteína Forkhead Box O1 , Glucosa , Estrés Oxidativo , Oxígeno/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Daño por Reperfusión/metabolismo , Transducción de Señal , Sirtuina 1/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
Ovarian torsion can be defined as the bending of the ovaries on the supporting ligament, disrupting both venous and arterial blood circulation. Insufficient blood flow causes ovarian tissue hypoxia and leads to ischemia. This study aimed to investigate whether tocilizumab has a protective effect on ischemia-reperfusion injury due to ovarian torsion in rats. Eighteen female Wistar albino rats were divided into three equal groups (Sham (SG), ischemia-reperfusion (OIR), and ischemia-reperfusion+tocilizumab (OIRT)). Degeneration, necrosis, vascular dilatation/congestion, interstitial edema, hemorrhage, and polymorphonuclear lymphocyte (PMNL) infiltration scores were significantly different between the groups (p=0.001 for all parameters). Moreover, the OIRT group had a significant improvement in these criteria compared to the OIR group (p<0.05). Additionally, there was a considerable difference between OIRT and OIR groups in the number of primordial, developing, and atretic follicles groups (p<0.05), while there was no difference in the number of corpus luteum (p=0.052). Stress markers or cytokines, such as MDA, tGSH, NF-κB, TNF-α, IL-1ß, and IL-6, were significantly different between groups (p<0.05). Furthermore, a significant improvement was found in the measured variables when the OIRT group was compared with the OIR group (p<0.05). Tocilizumab may be an alternative option for treating ischemia-reperfusion injury due to ovarian torsion.
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Enfermedades del Ovario , Daño por Reperfusión , Animales , Humanos , Ratas , Femenino , Enfermedades del Ovario/tratamiento farmacológico , Enfermedades del Ovario/prevención & control , Enfermedades del Ovario/complicaciones , Torsión Ovárica/complicaciones , Ratas Wistar , Isquemia/complicaciones , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Daño por Reperfusión/etiología , Reperfusión/efectos adversos , Antioxidantes/farmacologíaRESUMEN
SUMMARY: One of the reasons for acute kidney damage is renal ischemia. Nevertheless, there are limited protective and therapeutic approaches for this problem. Diacerein is an anti-inflammatory drug characterized by numerous biological activities. We aimed to determine the ameliorative impact of diacerein on renal ischemia/reperfusion injury (I/R) condition, exploring the underlying mechanisms. Twenty-four male rats were allotted into four groups (n= 6): sham group; Diacerein (DIA) group; I/R group, in which a non-crushing clamp occluded the left renal pedicle for 45 min, and the right kidney was nephrectomized for 5 min before the reperfusion process; I/R + diacerein group, injected intraperitoneally with 50 mg diacerein/kg i.m 30 minutes prior to I/R operation. Ischemia/ reperfusion was found to affect renal function and induce histopathological alterations. The flow cytometry analysis demonstrated an elevated expression of innate and mature dendritic cells in I/R renal tissues. Moreover, upregulation in the expression of the inflammatory genes (TLR4, Myd88, and NLRP3), and overexpression of the pro-inflammatory cytokines (IL-1β), apoptotic (caspase-3) and pyroptotic (caspase-1) markers were observed in I/R-experienced animals. The aforementioned deteriorations were mitigated by pre-I/R diacerein treatment. Diacerein alleviated I/R-induced inflammation and apoptosis. Thus, it could be a promising protective agent against I/R.
La isquemia renal es una de los motivos del daño renal agudo. Sin embargo, los enfoques protectores y terapéuticos para este problema son limitados. La diacereína es un fármaco antiinflamatorio caracterizado por numerosas actividades biológicas. Nuestro objetivo fue determinar el impacto de mejora de la diacereína en la condición de lesión por isquemia/ reperfusión renal (I/R), explorando los mecanismos subyacentes. Veinticuatro ratas macho se distribuyeron en cuatro grupos (n= 6): grupo simulado; grupo de diacereína (DIA); grupo I/R, en el que una pinza no aplastante ocluyó el pedículo renal izquierdo durante 45 min, y el riñón derecho fue nefrectomizado durante 5 min antes del proceso de reperfusión; Grupo I/R + diacereína, inyectado por vía intraperitoneal con 50 mg de diacereína/kg i.m. 30 min antes de la operación I/R. Se encontró que la isquemia/ reperfusión afecta la función renal e induce alteraciones histopatológicas. El análisis de citometría de flujo demostró una expresión elevada de células dendríticas innatas y maduras en tejidos renales I/R. Además, se observó una regulación positiva en la expresión de los genes inflamatorios (TLR4, Myd88 y NLRP3) y una sobreexpresión de las citoquinas proinflamatorias (IL-1β), marcadores apoptóticos (caspasa-3) y piroptóticos (caspasa-1) en animales con experiencia en I/R. Los deterioros antes mencionados fueron mitigados por el tratamiento previo a la diacereína I/R. La diacereína alivió la inflamación y la apoptosis inducidas por I/R. Por lo tanto, podría ser un agente protector prometedor contra I/R.
Asunto(s)
Animales , Ratas , Daño por Reperfusión/tratamiento farmacológico , Antraquinonas/administración & dosificación , Enfermedades Renales/tratamiento farmacológico , Antiinflamatorios/administración & dosificación , Células Dendríticas/efectos de los fármacos , Daño por Reperfusión/inmunología , Transducción de Señal , FN-kappa B/metabolismo , Antraquinonas/inmunología , Apoptosis/efectos de los fármacos , Estrés Oxidativo , Receptor Toll-Like 4/metabolismo , Interleucina-1beta/metabolismo , Citometría de Flujo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamación , Inyecciones Intraperitoneales , Enfermedades Renales/inmunologíaRESUMEN
Metabolic syndrome (MetS) is a cluster of factors that increase the risk of developing diabetes, stroke, and heart failure. The pathophysiology of injury by ischemia/reperfusion (I/R) is highly complex and the inflammatory condition plays an important role by increasing matrix remodeling and cardiac apoptosis. Natriuretic peptides (NPs) are cardiac hormones with numerous beneficial effects mainly mediated by a cell surface receptor named atrial natriuretic peptide receptor (ANPr). Although NPs are powerful clinical markers of cardiac failure, their role in I/R is still controversial. Peroxisome proliferator-activated receptor α agonists exert cardiovascular therapeutic actions; however, their effect on the NPs' signaling pathway has not been extensively studied. Our study provides important insight into the regulation of both ANP and ANPr in the hearts of MetS rats and their association with the inflammatory conditions caused by damage from I/R. Moreover, we show that pre-treatment with clofibrate was able to decrease the inflammatory response that, in turn, decreases myocardial fibrosis, the expression of metalloprotease 2 and apoptosis. Treatment with clofibrate is also associated with a decrease in ANP and ANPr expression.
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Síndrome Metabólico , Daño por Reperfusión , Ratas , Animales , Factor Natriurético Atrial/metabolismo , PPAR alfa/agonistas , Clofibrato/farmacología , Síndrome Metabólico/complicaciones , Síndrome Metabólico/tratamiento farmacológico , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Receptores del Factor Natriurético Atrial/metabolismo , Péptidos Natriuréticos , Isquemia , Arritmias Cardíacas , Inflamación/tratamiento farmacológicoRESUMEN
BACKGROUND: Testicular torsion is a condition in which a testis rotates around its longitudinal axis and twists the spermatic cord. This in turn results in a significant decrease in blood flow and perfusion of testicular tissue. During Testicular torsion, the testicular tissue is affected by ischemia, heat stress, hypoxia, and oxidative and nitrosative stress. The testicular torsion should be considered an emergency condition and surgical intervention (testicular detorsion ) as the sole treatment option in viable cases involves counter-rotation on twisted testes associated, when possible, to orchipexy, in order to avoid recurrence. Possible testicular detorsion side-effects occur due to reperfusion and endothelial cells injury, microcirculation disturbances, and intense germ cells loss. OBJECTIVES: To discuss testicular torsion surgery-based methods, different time frames for testicular torsion induction, and the associated pathophysiology by emphasizing cellular and molecular events as well as different therapeutic agent applications for testicular torsion. MATERIALS AND METHODS: We reviewed all original research and epidemiological papers related to testicular torsion condition. RESULTS: Testicular torsion causes germ cell necrosis, arrested spermatogenesis, and diminished testosterone levels, with consequent infertility. Among different involved pathophysiological impacts, testicular torsion/detorsion-induced ischemia seems to play the key role by leading the tissue toward other series of events in testis. Numerous studies have used adjuvant antioxidants, calcium channel blockers, anti-inflammatory agents, or vasodilating agents in order to decrease these effects. DISCUSSION AND CONCLUSION: To the best of our knowledge, no previously conducted study examined therapeutical agents' beneficial effects post clinical I/R condition in humans. Different agents targeting different pathophysiological conditions were used to ameliorate the ischemia/reperfusion-induced condition in animal models, however, none of the administrated agents were tested in human cases. Although considering testicular detorsion surgery is still the golden method to reverse the testicular torsion condition and the surgical approach is undeniable, the evaluated agents with beneficial effects, need to be investigated furthermore in clinical conditions. Thus, furthermore clinical studies and case reports are required to approve the animal models proposed agents' beneficial impacts.
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Daño por Reperfusión , Torsión del Cordón Espermático , Ratas , Masculino , Animales , Humanos , Torsión del Cordón Espermático/complicaciones , Células Endoteliales , Ratas Sprague-Dawley , Daño por Reperfusión/tratamiento farmacológico , TestículoRESUMEN
Animal models of cerebral ischemia have improved our understanding of the pathophysiology and mechanisms involved in stroke, as well as the investigation of potential therapies. The potential of zebrafish to model human diseases has become increasingly evident. The availability of these models allows for an increased understanding of the role of chemical exposure in human conditions and provides essential tools for mechanistic studies of disease. To evaluate the potential neuroprotective properties of minocycline against ischemia and reperfusion injury in zebrafish and compare them with other standardized models. In vitro studies with BV-2 cells were performed, and mammalian transient middle cerebral artery occlusion (tMCAO) was used as a comparative standard with the zebrafish stroke model. Animals were subjected to ischemia and reperfusion injury protocols and treated with minocycline. Infarction size, cytokine levels, oxidative stress, glutamate toxicity, and immunofluorescence for microglial activation, and behavioral test results were determined and compared. Administration of minocycline provided significant protection in the three stroke models in different parameters analyzed. Both experimental models complement each other in their particularities. The proposal also strengthens the findings in the literature in rodent models and allows the validation of alternative models so that they can be used in further research involving diseases with ischemia and reperfusion injury.
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Isquemia Encefálica , Fármacos Neuroprotectores , Daño por Reperfusión , Accidente Cerebrovascular , Animales , Humanos , Pez Cebra , Minociclina/farmacología , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Isquemia Encefálica/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Daño por Reperfusión/tratamiento farmacológico , Modelos Animales de Enfermedad , MamíferosRESUMEN
Purpose:Tau hyperphosphorylation is a modification frequently observed after brain ischemia which has been related to the aggregation of this protein, with subsequent cytoskeletal damage, and cellular toxicity. The present study tests the hypothesis of using glucosamine, an agent that increases protein O-GlcNAcylation, to decrease the levels of phosphorylation in Tau during ischemia-reperfusion.Material and methods: Transient focal ischemia was artificially induced in male Wistar rats by occlusion of the middle cerebral artery (MCAO) with an intraluminal monofilament. A single dose of intraperitoneal glucosamine of 200 mg/kg diluted in normal saline (SSN) was administered 60 min before ischemia. Histological brain sections were processed using indirect immunofluorescence with primary antibodies (anti-O-GlcNAc and anti pTau-ser 396). The Image J software was used to calculate the immunofluorescence signal intensity.Results: The phosphorylation of Tau at the serine residue 396 had a significant decrease with the administration of glucosamine during ischemia-reperfusion compared with the administration of placebo.Conclusions: These results show that glucosamine can reduce the phosphorylation levels of Tau in rodents subjected to ischemia and cerebral reperfusion, which implies a neuroprotective role of glucosamine.
Asunto(s)
Isquemia Encefálica , Fármacos Neuroprotectores , Daño por Reperfusión , Ratas , Animales , Masculino , Glucosamina/farmacología , Proteínas tau/metabolismo , Fosforilación , Ratas Wistar , Isquemia Encefálica/tratamiento farmacológico , Isquemia , Reperfusión , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Fármacos Neuroprotectores/farmacologíaRESUMEN
OBJECTIVE: None of studies have been conducted in terms of demonstrating the same effect with the low dose in cordycepin. In our study, we analyzed the histopathological and biochemical changes of low-dose Cordycepin(c) on a rat model in the kidney. MATERIALS AND METHODS: Twenty-four male Wistar Albino rats were randomly allocated to three groups (n = 8): the sham-control group (Group 1), the renal I/R-untreated (Group 2) group, and the I/R-C-treated (Group 3) group. Cordyceps was administered intraperitoneally at 5 mg/kg twice. Renal histological changes were compared and the relevant parameters of oxidative stress and inflammation were detected. RESULTS: In blood and tissue biochemistry, it was observed that IL-1 Beta, IL 6, TNF alpha, MDA, TOS, and OSI increased in Group 2 and decreased in Group 3. It was determined that TAS values were increased in Group 3, and decreased in Group 2. In the histopathological evaluation, while Group 1 was evaluated as normal, significant kidney damage was detected in Group 2. It was determined that there was a significant decrease in kidney damage in Group 3. CONCLUSION: These results suggest that low dose Cordycepin was as effective as normal dose on renal ischemic reperfusion and reduction of damage.
OBJETIVO: Ninguno de los estudios se ha realizado en términos de demostrar el mismo efecto con la dosis baja de cordicepina. En nuestro estudio, analizamos los cambios histopatológicos y bioquímicos de Cordycepin(c) en dosis bajas en un modelo de rata con isquemia-reperfusión (I/R) inducida en el riñón. MATERIALES Y MÉTODOS: Veinticuatro ratas macho Wistar Albino se asignaron al azar a tres grupos (n = 8): el grupo de control simulado (Grupo 1), el grupo sin tratamiento I/R renal (Grupo 2) y el grupo tratado con I/R-C (Grupo 3). Cordyceps se administró por vía intraperitoneal a 5 mg/kg dos veces. Se compararon los cambios histológicos renales y se detectaron los parámetros relevantes de estrés oxidativo e inflamación. RESULTADOS: En bioquímica sanguínea y tisular se observó que IL-1 Beta, IL 6, TNF alfa, MDA, TOS y OSI aumentaron en el Grupo 2 y disminuyeron en el Grupo 3. Se determinó que los valores de TAS aumentaron en el Grupo 3, y disminuyó en el Grupo 2. En la evaluación histopatológica, mientras que el Grupo 1 fue evaluado como normal, se detectó daño renal significativo en el Grupo 2. Se determinó que hubo una disminución significativa del daño renal en el grupo 3. CONCLUSIÓN: Estos resultados sugieren que la cordicepina en dosis bajas fue tan efectiva como la dosis normal en la reperfusión isquémica renal y la reducción del daño.
Asunto(s)
Cordyceps , Daño por Reperfusión , Animales , Ratas , Riñón , Ratas Wistar , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & controlRESUMEN
Liver ischemia-reperfusion (IR) injury is associated with poor outcome after liver transplantation and liver resections. Hexafluoroisopropanol (HFIP) is a tri-fluorinated metabolites of volatile anesthetics and has modulatory effects on inflammation that have been observed mainly in cell culture experiments. In this survey, we investigated the effects of HFIP in a rat model of normothermic hepatic ischemia-reperfusion injury. Twenty-four male Wistar rats were randomized into three groups: (1) control in which animals were submitted to 30 min of partial liver ischemia with resection of non-ischemic liver lobes immediate after reperfusion, (2) pre-ischemia (PI) group in which animals received intravenous HFIP (67 mg/kg) 5 min before liver ischemia, and (3) pre-reperfusion (PR) group in which animals received intravenous HFIP (67 mg/kg) 5 min before reperfusion. Four hours after reperfusion, all animals were euthanized for sample collection. Aspartate and alanine transaminases, glucose, and high mobility group box-1 (HMGB-1) protein concentrations showed a significant decreased, and malondialdehyde was increased in the PR group compared with control and PI groups. Interleukin 6 (IL-6) was increased in the PI group compared with control and PR groups. IL-10 and -12 were increased in the PR and PI groups, respectively, when compared with the control group. Glucose decreased in the PR when compared with the control group. Post-conditioning with HFIP led to a decrease in hepatocellular injury and was associated with a downregulation of HMGB-1. The HFIP resulted in a better control of inflammatory response to ischemia-reperfusion even without causing a reduction in oxidative stress.
Asunto(s)
Daño por Reperfusión , Animales , Masculino , Ratas , Regulación hacia Abajo , Glucosa/metabolismo , Isquemia/complicaciones , Isquemia/metabolismo , Hígado/metabolismo , Ratas Wistar , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/etiología , Daño por Reperfusión/metabolismoRESUMEN
Ischemia-reperfusion injury (IRI) drives graft rejection and is the main cause of mortality after liver transplantation. During IRI, an intense inflammatory response marked by chemokine production and neutrophil recruitment occurs. However, few strategies are available to restrain this excessive response. Here, we aimed to interfere with chemokine function during IRI in order to disrupt neutrophil recruitment to the injured liver. For this, we utilized a potent glycosaminoglycan (GAG)-binding peptide containing the 30 C-terminal amino acids of CXCL9 (MIG30) that is able to inhibit the binding of chemokines to GAGs in vitro. We observed that mice subjected to IRI and treated with MIG30 presented significantly lower liver injury and dysfunction as compared to vehicle-treated mice. Moreover, the levels of chemokines CXCL1, CXCL2 and CXCL6 and of proinflammatory cytokines TNF-α and IL-6 were significantly reduced in MIG30-treated mice. These events were associated with a marked inhibition of neutrophil recruitment to the liver during IRI. Lastly, we observed that MIG30 is unable to affect leukocytes directly nor to alter the stimulation by either CXCL8 or lipopolysaccharide (LPS), suggesting that its protective properties derive from its ability to inhibit chemokine activity in vivo. We conclude that MIG30 holds promise as a strategy to treat liver IRI and inflammation.
Asunto(s)
Quimiocinas , Daño por Reperfusión , Animales , Quimiocinas/metabolismo , Isquemia/metabolismo , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Péptidos/metabolismo , Péptidos/farmacología , Reperfusión/efectos adversos , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/etiología , Daño por Reperfusión/prevención & controlRESUMEN
AIMS: The lung is an important target organ damage in intestinal ischemia/reperfusion (II/R), but mechanisms involved in II/R-induced pulmonary artery (PA) dysfunction, as well as its treatment, are not clear. The present study aimed to investigate the mechanisms involved in the II/R-induced PA dysfunction and a possible protective role of acute simvastatin pretreatment. MAIN METHODS: Male Wistar rats were subjected to occlusion of the superior mesenteric artery for 45 min followed by 2 h reperfusion (II/R) or sham-operated surgery (sham). In some rats, simvastatin (20 mg/kg, oral gavage) was administrated 1 h before II/R. KEY FINDINGS: II/R reduced acetylcholine-induced relaxation and phenylephrine-induced contraction of PA segments, which were prevented by acute simvastatin pretreatment in vivo or restored by inducible nitric oxide synthase (iNOS) inhibition in situ with 1400 W. Elevated reactive oxygen species (ROS) levels and higher nuclear translocation of nuclear factor kappa B (NFκB) subunit p65 were observed in PA of II/R rats and prevented by simvastatin. Moreover, simvastatin increased superoxide dismutase (SOD) activity and endothelial nitric oxide synthase (eNOS) expression in PA of the II/R group as well as prevented the increased levels of interleukin (IL)-1ß and IL-6 in lung explants following II/R. SIGNIFICANCE: The study suggests that pretreatment with a single dose of simvastatin prevents the II/R-induced increase of inflammatory factors and oxidative stress, as well as PA endothelial dysfunction and adrenergic hyporreactivity. Therefore, acute simvastatin administration could be therapeutic for pulmonary vascular disease in patients suffering from intestinal ischemic events.
Asunto(s)
Enfermedades Intestinales , Isquemia Mesentérica , Daño por Reperfusión , Animales , Enfermedades Intestinales/tratamiento farmacológico , Enfermedades Intestinales/prevención & control , Isquemia , Masculino , Óxido Nítrico Sintasa de Tipo II/metabolismo , Arteria Pulmonar/metabolismo , Ratas , Ratas Wistar , Reperfusión , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & control , Simvastatina/farmacologíaRESUMEN
Dexmedetomidine (DEX) is known to provide neuroprotection against cerebral ischemia and reperfusion injury (CIRI), but the exact mechanisms remain unclear. This study was conducted to investigate whether DEX pretreatment conferred neuroprotection against CIRI by inhibiting neuroinflammation through the JAK2/STAT3 signaling pathway. Middle cerebral artery occlusion (MCAO) was performed to establish a cerebral ischemia/reperfusion (I/R) model. Specific-pathogen-free male Sprague-Dawley rats were randomly divided into Sham, I/R, DEX, DEX+IL-6, and AG490 (a selective inhibitor of JAK2) groups. The Longa score, TTC staining, and HE staining were used to evaluate brain damage. ELISA was used to exam levels of TNF-α. Western blotting was used to assess the levels of JAK2, phosphorylated-JAK2 (p-JAK2), STAT3, and phosphorylated-STAT3 (p-STAT3). Our results suggested that both pretreatment with DEX and AG490 decreased the Longa score and cerebral infarct areas following cerebral I/R. After treatment with IL-6, the effects of DEX on abrogating these pathological changes were reduced. HE staining revealed that I/R-induced neuronal pathological changes were attenuated by DEX application, consistent with the AG490 group. However, these effects of DEX were abolished by IL-6. Furthermore, TNF-α levels were significantly increased in the I/R group, accompanied by an increase in the levels of the p-JAK2 and p-STAT3. DEX and AG490 pretreatment down-regulated the expressions of TNF-α, p-JAK2, and p-STAT3. In contrast, the down-regulation of TNF-α, p-JAK2, and p-STAT3 induced by DEX was reversed by IL-6. Collectively, our results indicated that DEX pretreatment conferred neuroprotection against CIRI by inhibiting neuroinflammation via negatively regulating the JAK2/STAT3 signaling pathway.
Asunto(s)
Isquemia Encefálica , Dexmedetomidina , Daño por Reperfusión , Animales , Apoptosis , Isquemia Encefálica/complicaciones , Dexmedetomidina/farmacología , Dexmedetomidina/uso terapéutico , Interleucina-6/metabolismo , Janus Quinasa 2/metabolismo , Janus Quinasa 2/farmacología , Masculino , Enfermedades Neuroinflamatorias , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/complicaciones , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/farmacología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
INTRODUCTION: Medical improvements are needed to prevent ischemia-reperfusion injury in thoracoabdominal aortic surgery. The aim of this study was to determine the antioxidant effects of thymoquinone, silymarin, and curcumin against ischemia-reperfusion injury associated with abdominal aorta. METHODS: Twenty-five Wistar albino rats were included in the study. Sham, control, and treatment (thymoquinone, silymarin, and curcumin) groups were set in equal numbers. Ischemia-reperfusion was applied by clamping (120 minutes) and de-clamping (60 minutes) the infrarenal aorta of all groups, except the sham group. Before reperfusion, thymoquinone, silymarin, and curcumin were given intraperitoneally to the treatment groups. After reperfusion, blood samples were taken from the right ventricle. Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were studied in serum samples and histopathological examination was performed on the gastrocnemius muscle. RESULTS: There was a significant difference in TOS and OSI values between the control and sham groups. Both values were found higher in the control group than in the sham group (P<0.05). OSI values were found to be lower in the thymoquinone group compared to the control group (P<0.05). All three parameters were found to be lower in the silymarin group than in the control group (P<0.05). TAS and TOS levels were found to be higher in the curcumin group than in the control group (P<0.05). There was no histopathological difference between the groups. CONCLUSION: Silymarin and thymoquinone administration decreases oxidative stress in experimental aortic ischemia-reperfusion injury. Antioxidant effect of curcumin was lower than silymarin and thymoquinone.