scholarly journals Local anesthetic Ropivacaine protects rats from myocardial ischemia/reperfusion injury by inhibition of COX-2

2021 ◽  
Author(s):  
Zhou Yu ◽  
Sufang Sun ◽  
Fang Hu
Keyword(s):  
Oxidative Stress ◽  
Creatine Kinase ◽  
Ischemia Reperfusion ◽  
Inos Expression ◽  
Ischaemic Injury ◽  
Cardiac Tissues ◽  
Tnf Α ◽  
Creatine Kinase Mb ◽  
Cellular Apoptosis ◽  
Cox 2

IntroductionMyocardial ischaemia/reperfusion (I/R) injury is the leading cause of morbidity and mortality worldwide. Despite novel advances in therapeutics, the management of myocardial I/R is still an unmet medical need. Therefore, in the present study, we have demonstrated the protective effect of ropivacaine (RPC) on the myocardial infarction in rats and its underlying mechanism.Material and methodsInitially, the effect of RPC was determined on the infarct size and histopathology of cardiac tissues. The effect of RPC was also determined on the levels of various cardiac biomarkers such as creatine kinase (CK), creatine kinase MB (CK-MB), alanine aminotransferase (ALT), asparganine aminotransferase (AST), and lactate dehydrogenase (LDH), and biomarkers of oxidative stress (MDA, SOD, and GSH) and inflammation (tumour necrosis factor-α (TNF-α), interleukin 1β (IL-1β), and IL-6). RPC effect was also quantified on cellular apoptosis and COX-2 and iNOS expression via western blot analysis. The RPC was further docked into the active site of COX-2.ResultsIt has been found that RPC reduces the improves haemodynamics of (LVSP and ± dp/dtmax, and LVEDP), infarct percentage and architecture of cardiac tissues of rats. It also reduces the level of studies cardiac injury biomarkers together with a reduction of oxidative stress (MDA, SOD, and GSH) and inflammation (TNF-α, IL-1β, and IL-6). Upon administration of RPC, the rate of cellular apoptosis was found to be greatly reduced, with a reduction in COX-2 and iNOS expression. In docking analysis, RPC creates van der Waals forces and pi-interactions with Tyr381, Arg106, Val102, Leu345, Val509, Ser339, Leu338, Val335, Ala513, His75, and Leu517 at the catalytic site of COX-2.ConclusionsCollectively, our results demonstrated that ropivacaine showed significant benefit against myocardial ischaemic injury.

scholarly journals RNAi-Mediated Down-Regulation of CD47 Protects against Ischemia/Reperfusion-Induced Myocardial Damage via Activation of eNOS in a Rat Model

2016 ◽  
Vol 40 (5) ◽  
pp. 1163-1174 ◽  
Author(s):  
Hui-bo Wang ◽  
Jun Yang ◽  
Jia-wang Ding ◽  
Li-hua Chen ◽  
Song Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Creatine Kinase ◽  
Infarct Size ◽  
Rat Model ◽  
Ischemia Reperfusion ◽  
Myocardial Damage ◽  
Left Ventricular ◽  
Down Regulation ◽  
Creatine Kinase Mb

Background/Aims: Oxidative stress is strongly implicated in the pathogenesis of myocardial damage caused by ischemia reperfusion (I/R). Previous studies have confirmed that cardiac CD47 drives left ventricular heart failure. However, the role for CD47 in myocardial I/R injury (MIRI) has not previously been proposed. This study was designed to investigate whether down-regulation of CD47 using RNA interference (RNAi) technology can relieve inhibition of nitric oxide signaling and attenuate myocardial damage in a rat model of I/R. Methods: Male Sprague-Dawley rats (n = 40) were randomly allocated to four groups and pre-treated either with saline (Sham and I/R groups), or adenovirus expressing either control (Ad-EGFP-N) or CD47-targeting (Ad-EGFP-CD47) RNAi. After four days, the rat MIRI model was established by occluding the left anterior descending coronary artery for 30 min, followed by reperfusion for 3 h. Heart tissue was harvested and assessed by immunohistochemistry, western blot, and quantitative RT-PCR. Outcome measures included infarct size, myocardial enzyme (creatine kinase, creatine kinase-MB, and lactate dehydrogenase) levels in serum, markers of oxidative stress, and morphological changes to the myocardium. Results: Delivery of Ad-EGFP-CD47 RNAi into the myocardium remarkably decreased CD47 expression levels. Down-regulation of CD47 was significantly associated with reduced infarct size and serum levels of myocardial enzymes, increased activity of endothelial nitric oxide synthase, increased levels of nitric oxide, and decreased levels of oxidative stress. Conclusion: These data indicate that down-regulation of CD47 exerts a protective effect against MIRI, which may be attributable to attenuation of oxidative stress via activation of the eNOS/NO signaling pathway.

scholarly journals Targeting ROS/NF-κB sigaling pathway by the seedless black Vitis vinifera polyphenols in CCl4-intoxicated kidney, lung, brain, and spleen in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Noha H. Habashy ◽  
Ahmad S. Kodous ◽  
Marwa M. Abu-Serie
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Vitis Vinifera ◽  
Rat Kidney ◽  
Environmental Pollutant ◽  
Enhancing Effect ◽  
Tnf Α ◽  
Cox 2 ◽  
Histopathological Studies ◽  
And Oxidative Stress

AbstractCarbon tetrachloride (CCl4) is an abundant environmental pollutant that can generate free radicals and induce oxidative stress in different human and animal organs like the kidney, lung, brain, and spleen, causing toxicity. The present study evaluated the alleviative mechanism of the isolated polyphenolic fraction from seedless (pulp and skin) black Vitis vinifera (VVPF) on systemic oxidative and necroinflammatory stress in CCl4-intoxicated rats. Here, we found that the administration of VVPF to CCl4-intoxicated rats for ten days was obviously ameliorated the CCl4-induced systemic elevation in ROS, NO and TBARS levels, as well as MPO activity. Also, it upregulated the cellular activities of the enzymatic (SOD, and GPx) and non-enzymatic (TAC and GSH) antioxidants. Furthermore, the gene expression of the ROS-related necroinflammatory mediators (NF-κB, iNOS, COX-2, and TNF-α) in the kidney, brain, and spleen, as well as IL-1β, and IL-8 in the lung were greatly restored. The histopathological studies confirmed these biochemical results and showed a noticeable enhancing effect in the architecture of the studied organs after VVPF intake. Thus, this study indicated that VVPF had an alleviative effect on CCl4-induced necroinflammation and oxidative stress in rat kidney, lung, brain, and spleen via controlling the ROS/NF-κB pathway.

scholarly journals Honokiol ameliorates radiation-induced brain injury via the activation of SIRT3

2020 ◽  
Vol 48 (10) ◽  
pp. 030006052096399
Author(s):  
Guixiang Liao ◽  
Zhihong Zhao ◽  
Hongli Yang ◽  
Xiaming Li
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Inflammatory Responses ◽  
Tissue Injury ◽  
Interleukin 1 ◽  
Dependent Manner ◽  
Ht22 Cells ◽  
Tnf Α ◽  
Radiation Induced ◽  
Cox 2

Objective Sirtuin 3 (SIRT3) plays a vital role in regulating oxidative stress in tissue injury. The aim of this study was to evaluate the radioprotective effects of honokiol (HKL) in a zebrafish model of radiation-induced brain injury and in HT22 cells. Methods The levels of reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) were evaluated in the zebrafish brain and HT22 cells. The expression levels of SIRT3 and cyclooxygenase-2 (COX-2) were measured using western blot assays and real-time polymerase chain reaction (RT-PCR). Results HKL treatment attenuated the levels of ROS, TNF-α, and IL-1β in both the in vivo and in vitro models of irradiation injury. Furthermore, HKL treatment increased the expression of SIRT3 and decreased the expression of COX-2. The radioprotective effects of HKL were achieved via SIRT3 activation. Conclusions HKL attenuated oxidative stress and pro-inflammatory responses in a SIRT3-dependent manner in radiation-induced brain injury.

scholarly journals Zingerone produces antidiabetic effects and attenuates diabetic nephropathy by reducing oxidative stress and overexpression of NF-κB, TNF-α, and COX-2 proteins in rats

2020 ◽  
Vol 74 ◽  
pp. 104199
Author(s):  
Brahmjot Singh ◽  
Ajay Kumar ◽  
Hasandeep Singh ◽  
Sarabjit Kaur ◽  
Satwinderjeet Kaur ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Tnf Α ◽  
Cox 2 ◽  
Antidiabetic Effects

Activation of the MyD88 signaling pathway inhibits ischemia-reperfusion injury in the small intestine

2012 ◽  
Vol 303 (3) ◽  
pp. G324-G334 ◽  
Author(s):  
Toshio Watanabe ◽  
Atsushi Kobata ◽  
Tetsuya Tanigawa ◽  
Yuji Nadatani ◽  
Hirokazu Yamagami ◽  
...  
Keyword(s):  
Small Intestine ◽  
Signaling Pathway ◽  
Knockout Mice ◽  
Ischemia Reperfusion ◽  
Adaptor Protein ◽  
Myeloperoxidase Activity ◽  
Wild Type ◽  
Tnf Α ◽  
Cox 2 ◽  
Myd88 Signaling

Toll-like receptors (TLRs) recognize microbial components and trigger the signaling cascade that activates innate and adaptive immunity. Recent studies have shown that the activation of TLR-dependent signaling pathways plays important roles in the pathogenesis of ischemia-reperfusion (I/R) injuries in many organs. All TLRs, except TLR3, use a common adaptor protein, MyD88, to transduce activation signals. We investigated the role of MyD88 in I/R injury of the small intestine. MyD88 and cyclooxygenase-2 (COX-2) knockout and wild-type mice were subjected to intestinal I/R injury. I/R-induced small intestinal injury was characterized by infiltration of inflammatory cells, disruption of the mucosal epithelium, destruction of villi, and increases in myeloperoxidase activity and mRNA levels of TNF-α and the IL-8 homolog KC. MyD88 deficiency worsened the severity of I/R injury, as assessed using the histological grading system, measuring luminal contents of hemoglobin (a marker of intestinal bleeding), and counting apoptotic epithelial cells, while it inhibited the increase in mRNA expression of TNF-α and KC. I/R significantly enhanced COX-2 expression and increased PGE2 concentration in the small intestine of wild-type mice, which were markedly inhibited by MyD88 deficiency. COX-2 knockout mice were also highly susceptible to intestinal I/R injury. Exogenous PGE2 reduced the severity of injury in both MyD88 and COX-2 knockout mice to the level of wild-type mice. These findings suggest that the MyD88 signaling pathway may inhibit I/R injury in the small intestine by inducing COX-2 expression.

scholarly journals Ginsenoside Rb1 for Myocardial Ischemia/Reperfusion Injury: Preclinical Evidence and Possible Mechanisms

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Qun Zheng ◽  
Xiao-Yi Bao ◽  
Peng-Chong Zhu ◽  
Qiang Tong ◽  
Guo-Qing Zheng ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Creatine Kinase ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ginsenoside Rb1 ◽  
Creatine Kinase Mb ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Ginseng is an important herbal drug that has been used worldwide for many years. Ginsenoside Rb1 (G-Rb1), the major pharmacological extract from ginseng, possesses a variety of biological activities in the cardiovascular systems. Here, we conducted a preclinical systematic review to investigate the efficacy of G-Rb1 for animal models of myocardial ischemia/reperfusion injury and its possible mechanisms. Ten studies involving 211 animals were identified by searching 6 databases from inception to May 2017. The methodological quality was assessed by using the CAMARADES 10-item checklist. All the data were analyzed using RevMan 5.3 software. As a result, the score of study quality ranged from 3 to 7 points. Meta-analyses showed that G-Rb1 can significantly decrease the myocardial infarct size and cardiac enzymes (including lactate dehydrogenase, creatine kinase, and creatine kinase-MB) when compared with control group (P<0.01). Significant decrease in cardiac troponin T and improvement in the degree of ST-segment depression were reported in one study (P<0.05). Additionally, the possible mechanisms of G-Rb1 for myocardial infarction are antioxidant, anti-inflammatory, antiapoptosis, promoting angiogenesis and improving the circulation. Thus, G-Rb1 is a potential cardioprotective candidate for further clinical trials of myocardial infarction.

scholarly journals Danhong Injection Attenuates Cerebral Ischemia-Reperfusion Injury in Rats Through the Suppression of the Neuroinflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Haixia Du ◽  
Yu He ◽  
Yuanjiang Pan ◽  
Mengdi Zhao ◽  
Zhiwei Li ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Danhong Injection ◽  
Cerebral Ischemia Reperfusion ◽  
Tnf Α ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Cox 2

Neuroinflammation is one of the major causes of damage of the central nervous system (CNS) and plays a vital role in the pathogenesis of cerebral ischemia, which can result in long-term disability and neuronal death. Danhong injection (DHI), a traditional Chinese medicine injection, has been applied to the clinical treatment of cerebral stoke for many years. In this study, we investigated the protective effects of DHI on cerebral ischemia-reperfusion injury (CIRI) in rats and explored its potential anti-neuroinflammatory properties. CIRI in adult male SD rats was induced by middle cerebral artery occlusion (MCAO) for 1 h and reperfusion for 24 h. Results showed that DHI (0.5, 1, and 2 ml/kg) dose-dependently improved the neurological deficits and alleviated cerebral infarct volume and histopathological damage of the cerebral cortex caused by CIRI. Moreover, DHI (0.5, 1, and 2 ml/kg) inhibited the mRNA expressions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), intercellular cell adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in ischemic brains, downregulated TNF-α, IL-1β, and monocyte chemotactic protein-1 (MCP-1) levels in serum, and reduced the neutrophil infiltration (myeloperoxidase, MPO) in ischemic brains, in a dose-dependent manner. Immunohistochemical staining results also revealed that DHI dose-dependently diminished the protein expressions of ICAM-1 and COX-2, and suppressed the activation of microglia (ionized calcium-binding adapter molecule 1, Iba-1) and astrocyte (glial fibrillary acidic protein, GFAP) in the cerebral cortex. Western blot analysis showed that DHI significantly downregulated the phosphorylation levels of the proteins in nuclear factor κB (NF-κB) and mitogen-activated protein kinas (MAPK) signaling pathways in ischemic brains. These results indicate that DHI exerts anti-neuroinflammatory effects against CIRI, which contribute to the amelioration of CNS damage.

scholarly journals Bone marrow mesenchymal stem cells stimulated by tumor necrosis factor-α can promote the repair of fatty liver cell oxidative stress injury and fatty liver ischemia-reperfusion injury

2021 ◽  
Author(s):  
Yuying Tan ◽  
Jiali Qiu ◽  
Weiqi Zhang ◽  
Yan Xie ◽  
Chiyi Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Fatty Liver ◽  
Liver Cell ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Stress Injury ◽  
Oxidative Stress Injury ◽  
Tnf Α

Mesenchymal stem cells (MSCs) have great prospects for the treatment of ischemia-reperfusion injury (IRI) after liver transplantation. At this stage, the main factor limiting MSCs in the treatment of fatty liver IRI of the donor liver is the residence time of stem cells at the site of inflammatory injury. This study investigated whether bone marrow mesenchymal stem cells (BMSCs) stimulated by tumor necrosis factor-α (TNF-α) can promote the repair of fatty liver cell oxidative stress injury and fatty liver IRI in rats. The results indicated the BMSCs treatment group stimulated by TNF-α had lower indexes and significantly improved oxidative stress damage in vitro through Transwell chamber co-culture experiment, compared with the control group. In vivo, compared with the PBS group and the BMSCs group, the indexes of the BMSCs treatment group stimulated by TNF-α were reduced, and the degree of tissue damage was significantly reduced. BMSCs can repair fatty liver cell oxidative stress injury and fatty liver IRI, however, BMSCs stimulated by TNF-α can promote the repair of tissues and cells.

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