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1.
Biol. Res ; 53: 27, 2020. graf
Article in English | LILACS | ID: biblio-1124212

ABSTRACT

BACKGROUND: Circular RNA (circRNA) is highly expressed in the brain tissue, but its molecular mechanism in cerebral ischemia-reperfusion remains unclear. Here, we explored the role and underlying mechanisms of circRNA antisense non-coding RNA in the INK4 locus (circ_ANRIL) in oxygen-glucose deprivation and reoxygenation (OGD/R)-induced cell injury. RESULTS: The expression of circ_ANRIL in OGD/R-induced human brain microvascular endothelial cells (HBMECs) was significantly up-regulated, while that of miR-622 was significantly down-regulated. Overexpression of circ_ANRIL significantly inhibited the proliferation of OGD/R-induced HBMECs and aggravated OGD/R-induced cell apoptosis. Moreover, circ_ANRIL overexpression further increased the secretion of interleukin (IL)-1ß, IL-6, tumor necrosis factor-a, and monocyte chemoattractant protein-1 in OGD/R-treated HBMECs. The results of bioinformatics analysis and luciferase reporter assay indicated that circ_ANRIL served as an miR-622 sponge to negatively regulate the expression of miR-622 in OGD/R-treated HBMECs. Additionally, circ_ANRIL silencing exerted anti-apoptotic and anti-inflammatory effects by positively regulating the expression of miR-622. Furthermore, inhibition of OGD/R-induced activation of the nuclear factor (NF)-kB pathway by circ_ANRIL silencing was significantly reversed by treatment with miR-622 inhibitor. CONCLUSIONS: Knockdown of circ_ANRIL improved OGD/R-induced cell damage, apoptosis, and inflammatory responses by inhibiting the NF-κB pathway through sponging miR-622.


Subject(s)
Humans , Reperfusion Injury/metabolism , Hypoxia, Brain/metabolism , MicroRNAs/physiology , MicroRNAs/genetics , RNA, Circular , Oxygen , Brain , Apoptosis , Cyclin-Dependent Kinase Inhibitor p16 , Endothelial Cells , RNA, Long Noncoding , Glucose/metabolism , Inflammation
2.
Chinese Medical Journal ; (24): 2599-2609, 2020.
Article in English | WPRIM | ID: wpr-877854

ABSTRACT

Mitochondrial injury and endoplasmic reticulum (ER) stress are considered to be the key mechanisms of renal ischemia-reperfusion (I/R) injury. Mitochondria are membrane-bound organelles that form close physical contact with a specific domain of the ER, known as mitochondrial-associated membranes. The close physical contact between them is mainly restrained by ER-mitochondria tethering complexes, which can play an important role in mitochondrial damage, ER stress, lipid homeostasis, and cell death. Several ER-mitochondria tethering complex components are involved in the process of renal I/R injury. A better understanding of the physical and functional interaction between ER and mitochondria is helpful to further clarify the mechanism of renal I/R injury and provide potential therapeutic targets. In this review, we aim to describe the structure of the tethering complex and elucidate its pivotal role in renal I/R injury by summarizing its role in many important mechanisms, such as mitophagy, mitochondrial fission, mitochondrial fusion, apoptosis and necrosis, ER stress, mitochondrial substance transport, and lipid metabolism.


Subject(s)
Endoplasmic Reticulum/metabolism , Endoplasmic Reticulum Stress , Humans , Mitochondria , Mitochondrial Membranes/metabolism , Mitophagy , Reperfusion Injury/metabolism
3.
Acta cir. bras ; 34(11): e201901102, Nov. 2019. tab, graf
Article in English | LILACS | ID: biblio-1054682

ABSTRACT

Abstract Purpose: To investigate the effect of Picroside II on testicular ischemia and reperfusion (l/R) injury and the underlying mechanism. Methods: Sprague-Dawley rats were randomly divided into 4 groups: sham operated group (Sham), Sham with Picroside II treatment group (Sham+ Pic II), l/R group (l/R) and l/R with Picroside II treatment group (I/R+ Pic II). l/R model was established by rotating the left testis 720° in a clock-wise direction for 4 hours. The histopathologic and spermatogenetic evaluation was performed. The apoptosis changes and the levels of HO-1 (heme oxygenase-1), MPO (myeloperoxidase), NOX (NADPH oxidase), SOD (superoxide dismutase), XO (xanthine oxidase) and NOS (nitric oxide synthase) were measured. Results: The seminiferous tubules were damaged in l/R rats, but Picroside II alleviated the changes induced by l/R. The increased level of apoptosis was decreased by Picroside II (P=0.01, 9.05±0.35 vs. 4.85±0.25). The activities of HO-1, MPO, NOX, XO and MDA content were increased and the SOD activity was decreased in l/R (P<0.05) and could be reversed by Picroside II (P=0.03, 405.5±7.5 vs. 304±17U/mgprot; P=0.02, 0.99±0.05 vs. 0.52±0.04 mgprot; P=0.01, 260+7 vs. 189±2 mgprot; P=0.04, 10.95+0.55 vs. 8.75+0.35 U/mgprot; P=0.045, 6.8+0.7 vs. 3.75+0.35 mgprot; P=0.04, 44.5+3.5 vs. 57.5+3.5 mgprot). Western blot showed that the expression of iNOS, nNOS and eNOS were increased in l/R (P<0.05); however, they were decreased after Picroside II treatment (P<0.05). Conclusion: Picroside II attenuated testicular I/R injury in rats mainly through suppressing apoptosis and oxidative stress through reduction of nitric oxide synthesis.


Subject(s)
Animals , Male , Testis/blood supply , Reperfusion Injury/prevention & control , Cinnamates/pharmacology , Apoptosis/drug effects , Oxidative Stress/drug effects , Iridoid Glucosides/pharmacology , Nitric Oxide/biosynthesis , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Random Allocation , Blotting, Western , Rats, Sprague-Dawley , Peroxidase/analysis , In Situ Nick-End Labeling , Heme Oxygenase-1/analysis , Malondialdehyde/analysis , NADP/analysis
4.
Acta cir. bras ; 34(10): e201901003, Oct. 2019. tab, graf
Article in English | LILACS | ID: biblio-1054672

ABSTRACT

Abstract Purpose: To evaluate that Connexin (Cx43) plays a role in lesions after hepatic ischemia/reperfusion (IR) injury. Methods: We use Cx43 deficient model (heterozygotes mice) and compared to a wild group. The groups underwent 1 hour ischemia and 24 hours reperfusion. The heterozygote genotype was confirmed by PCR. We analyzed the hepatic enzymes (AST, ALT, GGT) and histology. Results: The mice with Cx43 deficiency showed an ALT mean value of 4166 vs. 307 in the control group (p<0.001); AST mean value of 7231 vs. 471 in the control group (p<0.001); GGT mean value of 9.4 vs. 1.7 in the control group (p=0.001); histology showed necrosis and inflammation in the knockout group. Conclusions: This research demonstrated that the deficiency of Cx43 worses the prognosis for liver injury. The topic is a promising target for therapeutics advancements in liver diseases and procedures.


Subject(s)
Animals , Reperfusion Injury/metabolism , Connexin 43/deficiency , Disease Models, Animal , Liver/blood supply , Aspartate Aminotransferases/analysis , Reference Values , Time Factors , Reperfusion Injury/pathology , Polymerase Chain Reaction , Mice, Knockout , Connexin 43/analysis , Alanine Transaminase/analysis , Genotyping Techniques , gamma-Glutamyltransferase/analysis , Liver/pathology , Necrosis
5.
Acta cir. bras ; 34(1): e20190010000005, 2019. graf
Article in English | LILACS | ID: biblio-983682

ABSTRACT

Abstract Purpose: To investigate the role of PI3k/Akt signal pathway in the protective effects of propofol on intestinal and lung injury induced by intestinal ischemia/reperfusion(I/R). Methods: Male Sprague-Dawley rats were subjected to 45 min of ischemia by occluding the superior mesenteric artery and to 2h of reperfusion to establish the model of I/R. Twenty four rats were randomly divided into four groups: Sham, intestinal I/R (II/R), propofol (P), wortmannin (W). In groups P, W, propofol was injected intravenously and continuously at the onset of reperfusion via infusion pump. PI3K inhibitor (wortmannin) was administered intravenously in group W 25 min before ischemia. Intestinal tissues and lung tissues were obtained for determination of histologic injury, wet/dry weight ratio, malondialdehyde (MDA) levels, superoxide dismutase (SOD) and myeloperoxidase (MPO) activities. Meanwhile, the expressions of caspase-3 and phosphorylated Akt (p-Akt) in intestines and lungs were detected by western blot. Results: Propofol treatment alleviated intestinal and lung morphological changes which were observed in II/R group,Moreover, wet/dry weight ratio, the MDA level, MPO activity and expression of caspase-3 were significantly decreased whereas the SOD activity and p-Akt expression were significantly increased. Notably, the protections were significantly reversed by pretreatment of wortmannin. Conclusion: PI3K/Akt pathway activation play a critical role in the protective effects of propofol on intestinal and lung injury induced by ischemia/reperfusion.


Subject(s)
Animals , Male , Rats , Reperfusion Injury/drug therapy , Propofol/pharmacology , Anesthetics, Intravenous/pharmacology , Phosphatidylinositol 3-Kinases/physiology , Proto-Oncogene Proteins c-akt/physiology , Lung Injury/prevention & control , Mesenteric Ischemia/drug therapy , Reperfusion Injury/metabolism , Signal Transduction/physiology , Rats, Sprague-Dawley , Disease Models, Animal , Mesenteric Ischemia/metabolism
6.
Biol. Res ; 52: 32, 2019. graf
Article in English | LILACS | ID: biblio-1038783

ABSTRACT

BACKGROUND: Long non-coding RNA H19 (H19) plays an important role by regulating protein expression in different tissues and organs of the body. However, whether H19 induces hypoxia/reoxygenation (h/R) injury via increase of autophagy in the hepatoma carcinoma cells is unknown. RESULTS: H19 was expressed in the hepatoma carcinoma cells (Hep G2 and HCCLM3 cells) and its expression was most in 8 h/24R. The knockdown of H19 and 3-MA (an autophagy inhibitor) protected against h/R-induced apoptosis, cell damage, the expression of cleaved caspase-3 and cleaved caspase-9, the release of cytochrome c (Cyt c). The knockdown of H19 and 3-MA also decreased the autophagic vesicles (AVs) and the expression of Beclin-1 and the ration of LC3-II/LC3-I, and increased cell viability, the expression of Bcl-2 and P62 and the phosphorylation of PI3K, Akt and mTOR. In addition, chloroquine (CQ, an inhibitor of autophagy flux) markedly decreased formation of autophagy flux (the ration of LC3-II/LC3-I). The results of the knockdown of H19 group were similar to those of the 3-MA (or CQ) group. Rapamycin (a mTOR inhibitor, an autophagy activator) further down-regulated h/R-induced decrease of the phosphorylated PI3K, Akt and mTOR. The knockdown of H19 cancelled the effect of rapamycin. The overexpression of H19 further expanded h/R-induced increase of the ration of LC3-II/LC3-I and decrease of the phosphorylated PI3K, Akt and mTOR. CONCLUSIONS: Our results suggest that the long non-coding RNA H19 induces h/R injury by up-regulation of autophagy via activation of PI3K-Akt-mTOR pathway in the hepatoma carcinoma cells.


Subject(s)
Humans , Reperfusion Injury/metabolism , Carcinoma, Hepatocellular/metabolism , RNA, Long Noncoding/metabolism , Liver Neoplasms/metabolism , Hypoxia/metabolism , Oxygen/metabolism , Autophagy/drug effects , Up-Regulation/physiology , Brain Ischemia/metabolism , Apoptosis/physiology , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology
7.
Acta cir. bras ; 33(12): 1043-1051, Dec. 2018. graf
Article in English | LILACS | ID: biblio-973484

ABSTRACT

Abstract Purpose: To analyze the effect of methylene blue (MB) therapy during the liver ischemia-reperfusion injury (I/R) process. Methods: Thirty-five male Wistar rats were used, (70%) submitted to partial ischemia (IR) or not (NIR) (30%) were obtained from the same animal. These animals were divided into six groups: 1) Sham (SH), 2) Sham with MB (SH-MB); 3) I/R, submitted to 60 minutes of partial ischemia and 15 minutes of reperfusion; 4) NI/R, without I/R obtained from the same animal of group I/R; 5) I/R-MB submitted to I/R and MB and 6) NI/R-MB, without I/R. Mitochondrial function was evaluated. Osmotic swelling of mitochondria as well as the determination of malondialdehyde (MDA) was evaluated. Serum (ALT/AST) dosages were also performed. MB was used at the concentration of 15mg/kg, 15 minutes before hepatic reperfusion. Statistical analysis was done by the Mann Whitney test at 5%. Results: State 3 shows inhibition in all ischemic groups. State 4 was increased in all groups, except the I/R-MB and NI/R-MB groups. RCR showed a decrease in all I/R and NI/R groups. Mitochondrial osmotic swelling showed an increase in all I/R NI/R groups in the presence or absence of MB. About MDA, there was a decrease in SH values in the presence of MB and this decrease was maintained in the I/R group. AST levels were increased in all ischemic with or without MB. Conclusions: The methylene blue was not able to restore the mitochondrial parameters studied. Also, it was able to decrease lipid peroxidation, preventing the formation of reactive oxygen species.


Subject(s)
Humans , Animals , Male , Reperfusion Injury/prevention & control , Enzyme Inhibitors/therapeutic use , Liver/blood supply , Methylene Blue/therapeutic use , Oxygen Consumption , Aspartate Aminotransferases/blood , Reference Values , Time Factors , Mitochondria, Liver/drug effects , Mitochondria, Liver/metabolism , Lipid Peroxidation/drug effects , Reperfusion Injury/metabolism , Reproducibility of Results , Reactive Oxygen Species/analysis , Reactive Oxygen Species/metabolism , Rats, Wistar , Cell Respiration , Alanine Transaminase/blood , Enzyme Inhibitors/pharmacology , Mitochondrial Membranes/drug effects , Mitochondrial Membranes/metabolism , Liver/metabolism , Malondialdehyde/analysis , Methylene Blue/pharmacology , Mitochondrial Swelling/drug effects
8.
Acta cir. bras ; 33(10): 889-895, Oct. 2018. tab
Article in English | LILACS | ID: biblio-973469

ABSTRACT

Abstract Purpose: To investigate the role of the exogenous supply of adenosine triphosphate (ATP) in the expression of Bax and Bcl2L1 genes in intestinal ischemia and reperfusion (IR) in rats. Methods: The study was designed as a randomized controlled trial with a blinded assessment of the outcome. Eighteen adult male Wistar-EPM1 rats were housed under controlled temperature and light conditions (22-23°C, 12 h light/dark cycle). The animals were randomly divided into 3 groups: 1. Sham group (SG): no clamping of the superior mesenteric artery; 2. Ischemia and reperfusion group (IRG): 3. Ischemia and reperfusion plus ATP (IRG + ATP). ATP was injected in the femoral vein before and after ischemia. Afterwards, intestinal segments were appropriately removed and processed for Endothelial Cell Biology Rat RT2 Profiler PCR Array. Results: ATP promoted the upregulation of Bcl2L1 gene expression, whereas it did not have significant effects on Bax gene expression. In addition, the relation of Bax/Bcl2L1 gene expression in the IRG group was 1.39, whereas it was 0.43 in the IRG + ATP group. Bcl2L1 plays a crucial role in protecting against intestinal apoptosis after ischemia and reperfusion. Increased Bcl2L1 expression can inhibit apoptosis while decreased Bcl2L1 expression can trigger apoptosis. Conclusion: Adenosine triphosphate was associated with antiapoptotic effects on the rat intestine ischemia and reperfusion by upregulating of Bcl2L1 gene expression.


Subject(s)
Animals , Male , Rats , Adenosine Triphosphate/pharmacology , Apoptosis/drug effects , Genes, bcl-2 , bcl-2-Associated X Protein/genetics , Ischemia/genetics , Reperfusion Injury/etiology , Reperfusion Injury/genetics , Reperfusion Injury/metabolism , Reperfusion Injury/drug therapy , Random Allocation , Gene Expression , Up-Regulation , Rats, Wistar , Proto-Oncogene Proteins c-bcl-2/metabolism , Disease Models, Animal , bcl-2-Associated X Protein/drug effects , bcl-2-Associated X Protein/metabolism , bcl-X Protein , Intestines , Ischemia/complications
9.
Acta cir. bras ; 33(9): 753-761, Sept. 2018. graf
Article in English | LILACS | ID: biblio-973501

ABSTRACT

Abstract Purpose: To evaluate the oxidative stress, resulting from ischemia and hepatic reperfusion, in mice with non-alcoholic hepatic steatosis and steatohepatitis. Methods: C57BL/6 male mice were used. Part of them were ob/ob mice, and the other part was fed with standard or MCD diets - this last used to develop steatohepatitis. The animals - MCD-I/R, ob/ob-I/R and I/R groups - were submitted to 30 minutes of partial hepatic ischemia, followed by reperfusion for 24 hours. The blood was collected, for biochemical analysis of AST, and the liver removed for assessment of TBARS and nitrite, and of histology. Results: After the I/R, the animal fed with MCD diet presented higher AST levels (MCD-I/R: 967±349U/L / ob/ob-I/R: 606±18 U/L / I/R: 311±172 U/L), TBARS (MCD-I/R: 7±1 nM/mg protein / ob/ob-I/R: 3±1 nM/mg protein / I/R: 3±1 nM/mg protein) and nitrite (MCD-I/R: 614±87 µg/mL / ob/ob-I/R: 512±81 µg/mL / I/R: 459±29 µg/mL) than the ob/ob mice, when both groups were compared to animals fed with standard diet. Regarding histology, the steatosis level (azonal macrovesicular steatosis of level 3 - >66%) and hepatic fibrosis (periportal and perisinusoidal of level 2) was also more intense, but both animal models presented lobular inflammation of level 3 (>66%). Conclusions: The murine model fed with MCD diet is suitable for the assessment of oxidative stress in hepatic I/R injury associated with the nonalcoholic fatty liver disease. Although both murine models showed inflammatory infiltrate and macro and micro vesicular steatosis.


Subject(s)
Animals , Male , Rats , Lipid Peroxidation/physiology , Reperfusion Injury/metabolism , Oxidative Stress/physiology , Non-alcoholic Fatty Liver Disease/metabolism , Nitrites/metabolism , Reperfusion Injury/pathology , Disease Models, Animal , Non-alcoholic Fatty Liver Disease/pathology , Mice, Inbred C57BL
10.
Acta cir. bras ; 33(8): 723-735, Aug. 2018. tab, graf
Article in English | LILACS | ID: biblio-949372

ABSTRACT

Abstract It is well known that during hepatic operative procedures, it is often critical that the irrigation is interrupted to avoid possible bleeding, blood transfusions, variable intensities, and their short and long-term consequences. It was believed in the past that the flow interruption should not exceed 20 minutes, which limited the use of this maneuver. However, it has been postulated that ischemia could be maintained for more than 60 minutes in healthy livers. The present paper review includes: 1) A brief introduction to justify the rationale of the review design; 2) Aspects of the pathophysiology of the three stages of the liver ischemia-reperfusion injury; 3) The innate and acquired immunity; 4) Oxidative stress; 5) Apoptosis and autophagy, Some essential biomarkers (Tumor Necrosis Factor-α, nitric oxide, metalloproteinases); and, finally; 6) Preventive ("cheating") strategies, non-pharmacological and pharmacological options to treat the liver IR injury.


Subject(s)
Humans , Reperfusion Injury/physiopathology , Reperfusion Injury/therapy , Ischemic Preconditioning/methods , Ischemia/physiopathology , Ischemia/therapy , Liver/blood supply , Time Factors , Mitochondria, Liver/metabolism , Reperfusion Injury/metabolism , Tumor Necrosis Factor-alpha/metabolism , Cell Death/physiology , Oxidative Stress/physiology , Matrix Metalloproteinases/metabolism , Ischemia/metabolism , Nitric Oxide/metabolism
11.
Acta cir. bras ; 33(8): 652-663, Aug. 2018. graf
Article in English | LILACS | ID: biblio-949377

ABSTRACT

Abstract Purpose: To evaluate histopathological and ultrastructural changes and expression of proteins related to apoptosis CASPASE 3 and XIAP after experimental induction of temporary focal cerebral ischemia (90 minutes) due to obstruction of the middle cerebral artery in alcoholism model. Methods: Forty adult Wistar rats were used, subdivided into 5 experimental groups: control group (C); Sham group (S); Ischemic group (I); Alcoholic group (A); and Ischemic and Alcoholized group (I+A): animals submitted to the same treatment of group A and after four weeks were submitted to focal cerebral ischemia during 90 minutes, followed by reperfusion of 48 hours. Were processed for histopathological analysis and immunohistochemistry (for the protein expression of CASPASE -3 and XIAP). Results: Greater histopathological changes were observed in the animals of groups I and I+A in the three areas analyzed. The neuronal loss was higher in the medial striatum region of the animals of groups I and I + A. The protein expression of CASPASE -3 was higher than that of XIAP in the groups I and I + A for both proteins. Conclusion: The expression of XIAP was slightly higher where the histopathological changes and expression of CASPASE -3 was less evident.


Subject(s)
Animals , Male , Ischemic Attack, Transient/pathology , Alcoholism/pathology , Inhibitor of Apoptosis Proteins/analysis , Caspase 3/analysis , Time Factors , Immunohistochemistry , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Random Allocation , Ischemic Attack, Transient/metabolism , Rats, Wistar , Apoptosis , Middle Cerebral Artery , Microscopy, Electron, Transmission , Alcoholism/metabolism , Edema , Electromyography/methods , Mitochondria/pathology
12.
Acta cir. bras ; 33(5): 462-471, May 2018. tab, graf
Article in English | LILACS | ID: biblio-949341

ABSTRACT

Abstract Purpose: To evaluate the effect of hyperbaric oxygenation (HBO) on the expression of the genes antioxidant glutathione peroxidase 4 (Gpx4) and lactoperoxidase (Lpo) in the lung of mice subjected to intestinal ischemia and reperfusion (IIR). Methods: Control group (CG) in which were subjected to anesthesia, laparotomy and observation for 120 minutes; an ischemia and reperfusion group (IRG) subjected to anesthesia, laparotomy, small bowel ischemia for 60 minutes and reperfusion for 60 minutes; and three groups treated with HBO during ischemia (HBOG + I), during reperfusion (HBOG + R) and during ischemia and reperfusion (HBOG + IR). Studied 84 genes of oxidative stress by the method (RT-qPCR). Genes with expression levels three times below or above the threshold cycle were considered significantly hypoexpressed or hyperexpressed, respectively (Student's t-test p<0.05). Results: Gpx4 and Lpo were hiperexpressed on IRG, showing a correlation with these genes with lung oxidative stress. Treated with HBO, there was a significant reduction on genic expression on HBOG+I. Conclusion: Hyperbaric oxygenation showed to be associated with decreased expression of these antioxidant genes, suggesting a beneficial effect on the mechanism of pulmonary oxidative stress whenever applied during the ischemia.


Subject(s)
Animals , Rats , Reperfusion Injury/metabolism , Oxidative Stress/genetics , Glutathione Peroxidase/metabolism , Hyperbaric Oxygenation/methods , Lactoperoxidase/genetics , Lung/metabolism , Oxidative Stress/drug effects , Disease Models, Animal , Intestines/blood supply , Ischemia/metabolism , Antioxidants/metabolism , Antioxidants/pharmacology
13.
Acta cir. bras ; 33(2): 117-124, Feb. 2018. tab, graf
Article in English | LILACS | ID: biblio-886260

ABSTRACT

Abstract Purpose: To observe the efficacy of phosphocreatine pre-administration (PCr-PA) on X-linked inhibitor of apoptosis protein (XIAP), the second mitochondia-derived activator of caspase (Smac) and apoptosis in the ischemic penumbra of rats with focal cerebral ischemia-reperfusion injury (CIRI). Methods: A total of 60 healthy male Sprague Dawley (SD) rats were randomly divided into three groups (n=20): group A (the sham operation group), group B <intraperitoneally injected with 20 mg/kg (10 mg/ml) of saline before preparing the ischemia-reperfusion (IR) model>, and group C <intraperitoneally injected with 20 mg/kg (10 mg/ml) of PCr immediately before preparing the IR model>. After 24 h for reperfusion, the neurological function was evaluated and the tissue was sampled to detect expression of XIAP, Smac and caspase-3 positive cells in the ischemic penumbra so as to observe the apoptosis. Results: Compared with group B, neurological deficit scores, numbers of apoptotic cells, expression of Smac,caspase-9 and the numbers of Caspase-3 positive cells were decreased while expression of XIAP were increased in the ischemic penumbra of group C. Conclusions: Phosphocreatine pre-administration may elicit neuroprotective effects in the brain by increasing expression of X-linked inhibitor of apoptosis protein, reducing expression of second mitochondia-derived activator of caspase, and inhibiting the apoptosis in the ischemic penumbra.


Subject(s)
Humans , Animals , Male , Rats , Phosphocreatine/pharmacology , Cardiotonic Agents/pharmacology , Reperfusion Injury/metabolism , Brain Ischemia/metabolism , Mitochondrial Proteins/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , X-Linked Inhibitor of Apoptosis Protein/metabolism , Random Allocation , Brain Ischemia/prevention & control , Rats, Sprague-Dawley , Apoptosis/drug effects , Neuroprotective Agents/pharmacology , Disease Models, Animal , Drug Evaluation, Preclinical , Apoptosis Regulatory Proteins , Caspase 3/metabolism
14.
Braz. j. med. biol. res ; 51(5): e7319, 2018. graf
Article in English | LILACS | ID: biblio-889079

ABSTRACT

MicroRNAs play a crucial role in the progression of spinal cord ischemia/reperfusion injury (SCII). The role of miR-448 and SIRT1 in SCII was investigated in this study, to provide further insights into prevention and improvement of this disorder. In this study, expressions of miR-448 and SIRT1 protein were determined by qRT-PCR and western blot, respectively. Flow cytometry was used to analyze cell apoptosis. The endogenous expression of genes was modulated by recombinant plasmids and cell transfection. Dual-luciferase reporter assay was performed to determine the interaction between miR-448 and SIRT1. The Basso, Beattie, and Bresnahan score was used to measure the hind-limb function of rat. The spinal cord ischemia reperfusion injury model of adult rats was developed by abdominal aorta clamping, and the nerve function evaluation was completed by motor deficit index score. In SCII tissues and cells treated with hypoxia, miR-448 was up-regulated while SIRT1 was down-regulated. Hypoxia treatment reduced the expression of SIRT1 through up-regulating miR-448 in nerve cells. Up-regulation of miR-448 induced by hypoxia promoted apoptosis of nerve cells through down-regulating SIRT1. Down-regulated miR-448 improved neurological function and hind-limb motor function of rats with SCII by up-regulating SIRT1. Down-regulated miR-448 inhibited apoptosis of nerve cells and improved neurological function by up-regulating SIRT1, which contributes to relieving SCII.


Subject(s)
Animals , Male , Rats , Reperfusion Injury/metabolism , Spinal Cord Ischemia/metabolism , MicroRNAs/metabolism , Sirtuin 1/metabolism , Transfection , Reperfusion Injury/physiopathology , Down-Regulation/physiology , Up-Regulation/physiology , Blotting, Western , Rats, Sprague-Dawley , Apoptosis , Reverse Transcriptase Polymerase Chain Reaction , Spinal Cord Ischemia/physiopathology , Disease Models, Animal , Flow Cytometry
15.
Acta cir. bras ; 32(11): 913-923, Nov. 2017. tab, graf
Article in English | LILACS | ID: biblio-886181

ABSTRACT

Abstract Purpose: To investigate the effects of hyperbaric oxygenation (HBO) on intestinal ischemia and reperfusion (IR) injury, we evaluated the expression of 84 genes related to oxidative stress and the antioxidant response in mouse hearts. Methods: Four groups were subjected to 60 minutes of intestinal ischemia followed by 60 minutes of reperfusion: IRG, ischemia and reperfusion group without HBO; HBO-IG, which received HBO during ischemia; HBO-RG, which received HBO during reperfusion; and HBO-IRG, which received HBO during ischemia and reperfusion. The control group (CG) underwent anesthesia and laparotomy and was observed for 120 minutes. The (RT-qPCR) method was applied. Genes with expression levels three times below or above the threshold cycle were considered significantly hypoexpressed or hyperexpressed, respectively (Student's t-test p<0.05). Results: Eight genes (9.52%) were hyperexpressed in the IRG. When the HBO groups were compared to the IRG, we found a decrease in the expression of eight genes in the HBO-IG, five genes in the HBO-RG, and seven genes in the HBO-IRG. Conclusion: The reduction in the expression of genes related to oxidative stress and antioxidant defense following HBO in mouse hearts resulting from intestinal IR injury was more favorable during the ischemic period than during the reperfusion period.


Subject(s)
Animals , Male , Mice , Reperfusion Injury/prevention & control , Gene Expression , Oxidative Stress/genetics , Hyperbaric Oxygenation/methods , Intestines/blood supply , Reperfusion Injury/metabolism , Polymerase Chain Reaction , Oxidative Stress/drug effects , NADPH Oxidases/metabolism , Coronary Vessels/enzymology , Disease Models, Animal , Heart , Heart Diseases , Ischemia/metabolism , Mice, Inbred C57BL , Antioxidants/metabolism , Antioxidants/pharmacology
16.
Acta cir. bras ; 32(6): 429-439, June 2017. graf
Article in English | LILACS | ID: biblio-886202

ABSTRACT

Abstract Purpose: To determine whether dexmedetomidine (DEX) could attenuate acute kidney injury (AKI) induced by ischemia/reperfusion (I/R) in streptozotocin (STZ)-induced diabetic rats. Methods: Four groups each containing six rats were created (sham control(S), diabetes-sham (DS), diabetes I/R (DI/R), and diabetes-I/R-dexmedetomidine (DI/R-DEX). In diabetes groups, single-dose (65 mg/kg) STZ was administered intraperitoneally (i.p.). In Group DI/R, ischemia reperfusion was produced via 25 min of bilateral renal pedicle clamping followed by 48 h of reperfusion. In Group DI/R-DEX, 50 μg/kg dexmedetomidine was administered intraperitoneally 30 minutes before ischemia. Renal function, histology, apoptosis, the levels of TNF-α, IL-1β, and oxidative stress in diabetic kidney were determined. Moreover, expression of P38 mitogen-activated protein kinase (P38-MAPK), phosphorylated-P38-MAPK(p-P38-MAPK) and thioredoxin-interacting protein (TXNIP) were assessed. Results: The degree of renal I/R injury was significantly increased in DI/R group compared with S group and DS group. The levels of TNF-α, IL-1β, oxidative stress and apoptosis were found significantly higher in DI/R Group when compared with S Group and DS Group. The protein expression of p-P38-MAPK and TXNIP were significantly increased after I/R. All these changes were reversed by DEX treatment. Conclusion: The renoprotective effects of DEX-pretreatment which attenuates I/R-induced AKI were partly through inhibition of P38-MAPK activation and expression of TXINP in diabetic kidney.


Subject(s)
Animals , Male , Rats , Reperfusion Injury/drug therapy , Protective Agents/therapeutic use , Dexmedetomidine/therapeutic use , Diabetes Mellitus, Experimental/complications , Kidney/drug effects , Reperfusion Injury/etiology , Reperfusion Injury/metabolism , Signal Transduction/drug effects , Carrier Proteins/drug effects , Carrier Proteins/metabolism , Rats, Sprague-Dawley , Streptozocin , p38 Mitogen-Activated Protein Kinases/drug effects , p38 Mitogen-Activated Protein Kinases/metabolism , Kidney/injuries , Kidney/pathology
17.
Acta cir. bras ; 32(6): 459-466, June 2017. tab, graf
Article in English | LILACS | ID: biblio-886207

ABSTRACT

Abstract Purpose: To investigate the effects of dexmedetomidine (DEX) on amino acid contents and the cerebral ultrastructure of rats with cerebral ischemia-reperfusion injury (I/R). Methods: Thirty-six, male, Wistar rats were randomly divided into three groups: the sham operation group (group C), the ischemia-reperfusion group (group I/R), and the DEX group (group D). The middle cerebral artery occlusion model was prepared by the modified Longa method. The time of ischemia was 180 min, and 120 min after reperfusion, the amount of glutamate (Glu), and γ-aminobutyric acid (GABA) in the brain were measured, and the ultrastructure-level changes in the cerebral cortex were examined using electron microscopy. Results: Compared to group C, Glu contents in group D, and I/R significantly increased. Compared to group I/R, Glu contents in group D significantly decreased. Compared to group C, GABA contents in group D, and I/R significantly increased, and those in group D significantly increased, as compared to group I/R. The cerebral ultrastructure was normal in group C. Vacuolar degeneration in the plastiosome and nervous processes, was more critical than in group D. Vascular endothelial cells (VEC) were damaged. On the contrary, these changes in group D significantly improved. Conclusion: Dexmedetomidine is capable of decreasing glutamergic content, and increasing GABAergic content, in order to decrease the injury of the cerebral ultrastructure, following cerebral ischemia-reperfusion injury.


Subject(s)
Animals , Male , Rats , Reperfusion Injury/metabolism , Cerebral Cortex/chemistry , Brain Ischemia/drug therapy , Neuroprotective Agents/pharmacology , Dexmedetomidine/pharmacology , Glutamine/metabolism , Cerebral Cortex/ultrastructure , Brain Ischemia/metabolism , Rats, Wistar , gamma-Aminobutyric Acid/drug effects , gamma-Aminobutyric Acid/metabolism , Amino Acids/drug effects , Amino Acids/metabolism
18.
Acta cir. bras ; 32(3): 229-235, Mar. 2017. tab, graf
Article in English | LILACS | ID: biblio-837690

ABSTRACT

Abstract Purpose: To evaluate the effects of tramadol hydrochloride associated to remote ischemic perconditioning on oxidative stress. Methods: Twenty five male rats (Wistar) underwent right nephrectomy and were distributed into five groups: Sham group (S); Ischemia/Reperfusion group (I/R) with 30 minutes of renal ischemia; Remote ischemic perconditioning group (Per) with three cycles of 10 minutes of I/R performed during kidney ischemia; Tramadol group (T) treated with tramadol hydrochloride (40mg/kg); remote ischemic perconditioning + Tramadol group (Per+T) with both treatments. Oxidative stress was assessed after 24 hours of reperfusion. Results: Statistical differences were observed in MDA levels between I/R group with all groups (p<0.01), in addition there was difference between Tramadol with Sham, Per and Per+T groups (p<0.05), both in plasma and renal tissue. Conclusion: Remote ischemic perconditioning was more effective reducing renal ischemia-reperfusion injury than administration of tramadol or association of both treatments.


Subject(s)
Animals , Male , Tramadol/pharmacology , Reperfusion Injury/prevention & control , Oxidative Stress/drug effects , Ischemic Preconditioning/methods , Protective Agents/pharmacology , Ischemia/prevention & control , Kidney/blood supply , Time Factors , Reperfusion Injury/metabolism , Random Allocation , Reproducibility of Results , Treatment Outcome , Rats, Wistar , Combined Modality Therapy/methods , Oxidative Stress/physiology , Ischemia/metabolism , Kidney/metabolism , Malondialdehyde/analysis
19.
Braz. j. med. biol. res ; 50(6): e5954, 2017. tab, graf
Article in English | LILACS | ID: biblio-839306

ABSTRACT

Salvianolic acid B (SAB) is one the major phytocomponents of Radix Salvia miltiorrhiza and exhibit numerous health promoting properties. The objective of the current study was to examine whether SAB exerts a renoprotective effect by attenuating oxidative stress and inflammatory response through activating phosphatidylinositol 3-kinase/serine-threonine kinase B (PI3K/Akt) signaling pathway in a renal ischemic reperfusion rat model. Forty Sprague-Dawley male rats (250–300 g) were obtained and split into four groups with ten rats in each group. The right kidney of all rats was removed (nephrectomy). The rats of the Control group received only saline (occlusion) and served as a sham control group, whereas rats subjected to ischemic reperfusion (IR) insult by clamping the left renal artery served as a postitive control group. The other 2 groups of rats were pretreated with SAB (20 and 40 mg·kg-1·day-1) for 7 days prior IR induction and served as treatment groups (SAB 20+IR; SAB 40+IR). Renal markers creatinine (Cr) and blood urea nitrogen (BUN) were significantly lower in the groups that received SAB. Pretreatment with SAB appears to attenuate oxidative stress by suppressing the production of lipid peroxidation products like malondialdehyde as well as elevating antioxidant activity. The concentration of inflammatory markers and neutrophil infiltration (myeloperoxidase) were significantly decreased. Meanwhile, PI3K protein expression and pAkt/Akt ratio were significantly upregulated upon supplementation with SAB, indicating its renoprotective activity. Taken together, these results indicate that SAB can therapeutically alleviate oxidative stress and inflammatory process via modulating PI3K/Akt signaling pathway and probably ameliorate renal function and thus act as a renoprotective agent.


Subject(s)
Animals , Male , Benzofurans/pharmacology , Drugs, Chinese Herbal/pharmacology , Oxidative Stress/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Protective Agents/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Reperfusion Injury/drug therapy , Blood Urea Nitrogen , Creatinine/metabolism , Inflammation/metabolism , Kidney/pathology , Lipid Peroxidation/drug effects , Peroxidase/drug effects , Rats, Sprague-Dawley , Reperfusion Injury/metabolism , Signal Transduction
20.
Acta cir. bras ; 31(12): 807-812, Dec. 2016. graf
Article in English | LILACS | ID: biblio-837655

ABSTRACT

ABSTRACT PURPOSE: To investigate the role of bradykinin in a rat lung transplantation (LTx) model and preliminarily discuss the relationship between bradykinin and CD26/DPP-4. METHODS: Rats were randomly divided into four groups: Control (CON), Sham, low potassium dextranglucose (LPD), and AB192 (n=15/group). Orthotopic single LTx was performed in the LPD and AB192 groups. The donor lungs were flush-perfused and preserved with low potassium dextranglucose (LPD) or LPD+CD26/DPP-4 catalytic inhibitor (AB192). LTx was performed after 18 h cold ischemia time and harvested two days post-LTx. Blood gas analysis (PO2), wet/dry weight ratio (W/D), myeloperoxidase activity (MPO), and lipid peroxidation (MDA) were analyzed at 48 hr after transplantation. Immunohistochemical (IHC) analysis was performed in the same sample and validated by Western-Blot. RESULTS: Compared to the LPD group, the AB192 group showed higher PO2, lower W/D ratio, and decreased MPO and MDA. IHC studies showed strong bradykinin β2 receptor (B2R) staining in the LPD group, especially in inflammatory cells, alveolar macrophages, and respiratory epithelial cells. Expression of B2R by Western-Blot was significantly different between the AB192 and LPD groups. CONCLUSION: Bradykinin may be a competitive substrate of DPP-4, and decreased bradykinin levels may enhance protective effects against ischemia/reperfusion injury during LTx.


Subject(s)
Animals , Male , Rats , Bradykinin/physiology , Reperfusion Injury/pathology , Lung Transplantation , Dipeptidyl Peptidase 4/physiology , Primary Graft Dysfunction/pathology , Lung/blood supply , Immunohistochemistry , Lipid Peroxidation , Reperfusion Injury/physiopathology , Reperfusion Injury/metabolism , Random Allocation , Blotting, Western , Disease Models, Animal , Primary Graft Dysfunction/physiopathology , Bradykinin B2 Receptor Antagonists/metabolism , Lung/drug effects
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