Minocycline inhibits apoptosis and inflammation in a rat model of ischemic renal injury

2004 ◽  
Vol 287 (4) ◽  
pp. F760-F766 ◽  
Author(s):  
K. J. Kelly ◽  
T. A. Sutton ◽  
N. Weathered ◽  
N. Ray ◽  
E. J. Caldwell ◽  
...  
Keyword(s):  
Rat Model ◽  
Renal Injury ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Treated Group ◽  
Cytochrome C Release ◽  
Ischemic Renal Injury ◽  
Anti Inflammatory ◽  
Apoptosis And Inflammation

Tetracyclines exhibit significant anti-inflammatory properties in a variety of rheumatologic and dermatologic conditions. They have also been shown to inhibit apoptosis in certain neurodegenerative disorders. Because ischemic renal injury is characterized by both apoptosis and inflammation, we investigated the therapeutic potential of tetracyclines in a rat model of renal ischemia-reperfusion. Male Sprague-Dawley rats underwent bilateral renal artery clamp for 30 min followed by reperfusion and received either minocycline or saline for 36 h before ischemia. Minocycline reduced tubular cell apoptosis 24 h after ischemia as determined by terminal transferase-mediated dUTP nick end-labeling staining and nuclear morphology. It also decreased cytochrome c release into the cytoplasm and reduced upregulation of p53 and Bax after ischemia. The minocycline-treated group showed a significant reduction in tubular injury and cast formation. In addition, minocycline reduced the number of infiltrating leukocytes, decreased leukocyte chemotaxis both in vitro and ex vivo, and downregulated the expression of ICAM-1. Serum creatinine 24-h postischemia was significantly reduced in the minocycline-treated group. We conclude that minocycline has potent antiapoptotic and anti-inflammatory properties and protects renal function in this model of ischemia-reperfusion. Tetracyclines are among the safest and best-studied antibiotics. They are thus attractive candidates for the therapy of human ischemic acute renal failure.

scholarly journals AB0069 LORECIVIVINT (SM04690), AN INTRA-ARTICULAR, SMALL-MOLECULE CLK/DYRK1A INHIBITOR THAT MODULATES THE WNT PATHWAY, AS A POTENTIAL TREATMENT FOR MENISCAL INJURIES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1335.2-1335
Author(s):  
T. Seo ◽  
V. Deshmukh ◽  
Y. Yazici
Keyword(s):  
Small Molecule ◽  
Rat Model ◽  
Wnt Pathway ◽  
Ex Vivo ◽  
Meniscal Tear ◽  
Knee Oa ◽  
Meniscus Degeneration ◽  
Anti Inflammatory ◽  
Meniscal Damage

Background:Meniscal injuries, associated with pain, stiffness, and localized swelling, are the most common pathology of the knee with a prevalence of 61 per 100,000.1Meniscal damage is a frequent finding on MRI images of knee osteoarthritis (OA)2; while a meniscal tear can lead to knee OA, knee OA can also lead to a spontaneous meniscal tear.3Efforts to repair meniscal damage have been largely unsuccessful and do not prevent the progression of degenerative changes that lead to knee OA.4The Wnt signaling pathway has been shown to be regulated during meniscal development,5,6suggesting that manipulation of this pathway may influence the regenerative capacity of the meniscus. Lorecivivint (LOR; SM04690) is an intra-articular (IA), small-molecule CLK/DYRK1A inhibitor that modulates the Wnt pathway.Objectives:LOR was evaluated in preclinical studies to determine its protective and anabolic effects in ex vivo explants and in a rat model of chemically induced inflammatory meniscus degeneration.Methods:Effects of LOR (30 nM) on expression of matrix metalloproteinases (MMPs) in cultured rat menisci treated with IL-1B were measured by qPCR. In vivo, LOR activity was evaluated in a rat model of monosodium iodoacetate (MIA) injection-induced inflammatory meniscus degeneration. A single IA injection of MIA was immediately followed by a single IA injection of LOR (0.3 ug) or vehicle. Knees were harvested on Days 1, 4, and 11 and menisci were isolated. Anti-inflammatory effects were evaluated by measuringTNFAandIL6expression by qPCR. Meniscus protection was evaluated by qPCR for MMPs and aggrecanase and anabolic effects by qPCR for collagens.Results:In ex vivo meniscal explants, LOR inhibited expression ofMMP1,MMP3, andMMP13compared to DMSO (P<0.01). In vivo, LOR significantly decreased expression of these MMPs and aggrecanase (P<0.05) compared to vehicle in the rat model of inflammatory meniscus degeneration at Day 4 after MIA injection. In addition, LOR reduced expression of inflammatory cytokinesTNFAandIL6at Day 4 compared to vehicle. Finally, LOR increased expression of collagen types I, II, and III at Day 11 after MIA injection.Conclusion:LOR exhibited protective effects in the meniscus ex vivo and in vivo by reducing the expression of catabolic enzymes compared to control. Anti-inflammatory effects of LOR were demonstrated by inhibition of inflammatory cytokine expression. Compared to vehicle, LOR increased expression of collagens in vivo, indicating potential meniscal anabolic effects. These data support further investigation of LOR as a potential disease-modifying therapy for meniscal injuries.References:[1]Logerstedt D and Snyder-Mackler L.J Orthop Sports Phys Ther. 2010[2]Englund M, et al.Rheum Dis Clin North Am. 2009[3]Englund M, et al.Radiol Clin North Am. 2009[4]von Lewinski, et al.Knee Surg Sports Traumatol Arthrosc. 2007[5]Pazin DE, et al.ORS 2012 Annual Meeting. Paper No. 0221[6]Pazin DE, et al.Dev Dyn. 2012Disclosure of Interests:Tim Seo Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, Vishal Deshmukh Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, Yusuf Yazici Shareholder of: Samumed, LLC, Grant/research support from: Bristol-Myers Squibb, Celgene, and Genentech, Consultant of: Celgene and Sanofi, Employee of: Samumed, LLC

scholarly journals Protective effects of Panax notoginseng saponins in a rat model of severe acute pancreatitis occur through regulation of inflammatory pathway signaling by upregulation of miR-181b

2018 ◽  
Vol 32 ◽  
pp. 205873841881863
Author(s):  
Ming-wei Liu ◽  
Yun-qiao Huang ◽  
Ya-ping Qu ◽  
Dong-mei Wang ◽  
Deng-yun Tang ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Rat Model ◽  
Therapeutic Potential ◽  
Sodium Taurocholate ◽  
Panax Notoginseng ◽  
Serum Levels ◽  
Panax Notoginseng Saponins ◽  
Tnf Α ◽  
Anti Inflammatory

Panax notoginseng saponins are extracted from Chinese ginseng— Panax notoginseng Ledeb—and are known to have therapeutic anti-inflammatory effects. However, the precise mechanism behind their anti-inflammatory effects remains relatively unknown. To better understand how Panax notoginseng saponins exert their therapeutic benefit, we tested them in a rat model of severe acute pancreatitis (SAP). Rats received a tail vein injection of Panax notoginseng saponins and were administered 5% sodium taurocholate 2 h later. Pancreatic tissue was then harvested and levels of miR-181b, FSTL1, TREM1, TLR4, TRAF6, IRAK1, p-Akt, p-p38MAPK, NF-κBp65, and p-IκB-α were determined using Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Enzyme-linked immunosorbent assays were used to determine serum levels of tumor necrosis factor-α (TNF-α), TREM1, interleukin (IL)-6, ACAM-1, IL-8, and IL-12 and DNA-bound levels of NF-KB65 and TLR4 in pancreatic and ileum tissue. Serum levels of lipase and amylase, pancreatic myeloperoxidase (MPO) activity, and pancreatic water content were also measured. Hematoxylin and eosin staining was used for all histological analyses. Results indicated upregulation of miR-181b, but negligible levels of FSTL1, p-p38MAPK, TLR4, TRAF6, p-Akt, IRAK1, TREM1, p-NF-κBp65, and p-IκB-α, as well as negligible DNA-bound levels of NF-KB65 and TLR4. We also observed lower levels of IL-8, IL-6, ACAM-1, TNF-α, MPO, and IL-12 in the Panax notoginseng saponin–treated group when compared with controls. In addition, Panax notoginseng saponin–treated rats had significantly reduced serum levels of lipase and amylase. Histological analyses confirmed that Panax notoginseng saponin treatment significantly reduced taurocholate-induced pancreatic inflammation. Collectively, our results suggest that Panax notoginseng saponin treatment attenuated acute pancreatitis and pancreatic inflammation by increasing miR-181b signaling. These findings suggest that Panax notoginseng saponins have therapeutic potential in the treatment of taurocholate-induced SAP.

scholarly journals Liposome/gold hybrid nanoparticle encoded with CoQ10 (LGNP-CoQ10) suppressed rheumatoid arthritis via STAT3/Th17 targeting

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241080
Author(s):  
Jooyeon Jhun ◽  
Jeonghyeon Moon ◽  
Jaeyoon Ryu ◽  
Yonghee Shin ◽  
Seangyoun Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mononuclear Cells ◽  
Therapeutic Potential ◽  
Human Peripheral Blood ◽  
Treated Group ◽  
Hybrid Nanoparticles ◽  
Peripheral Blood Mononuclear ◽  
Hematoxylin And Eosin ◽  
Anti Inflammatory ◽  
Safranin O

Coenzyme Q10 (CoQ10), also known as ubiquinone, is a fat-soluble antioxidant. Although CoQ10 has not been approved as medication by the Food and Drug Administration, it is widely used in dietary supplements. Some studies have shown that CoQ10 has anti-inflammatory effects on various autoimmune disorders. In this study, we investigated the anti-inflammatory effects of liposome/gold hybrid nanoparticles encoded with CoQ10 (LGNP-CoQ10). Both CoQ10 and LGNP-CoQ10 were administered orally to mice with collagen-induced arthritis (CIA) for 10 weeks. The inflammation pathology of joint tissues of CIA mice was then analyzed using hematoxylin and eosin and Safranin O staining, as well as immunohistochemistry analysis. We obtained immunofluorescence staining images of spleen tissues using confocal microscopy. We found that pro-inflammatory cytokines were significantly decreased in LGNP-CoQ10 injected mice. Th17 cell and phosphorylated STAT3-expressed cell populations were also decreased in LGNP-CoQ10 injected mice. When human peripheral blood mononuclear cells (PBMCs) were treated with CoQ10 and LGNP-CoQ10, the IL-17 expression of PBMCs in the LGNP-CoQ10-treated group was significantly reduced. Together, these results suggest that LGNP-CoQ10 has therapeutic potential for the treatment of rheumatoid arthritis.

scholarly journals Clinical Applications of Mesenchymal Stem/Stromal Cell Derived Extracellular Vesicles: Therapeutic Potential of an Acellular Product

Diagnostics ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 999
Author(s):  
Margherita Massa ◽  
Stefania Croce ◽  
Rita Campanelli ◽  
Carlotta Abbà ◽  
Elisa Lenta ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Large Scale ◽  
Therapeutic Potential ◽  
Ischemia Reperfusion ◽  
Clinical Stage ◽  
Kidney Injury ◽  
Scale Production ◽  
Bioactive Lipids ◽  
Anti Inflammatory ◽  
Signaling Receptors

In the last decade, the secreting activity of mesenchymal stem/stromal cells (MSCs) has been widely investigated, due to its possible therapeutic role. In fact, MSCs release extracellular vesicles (EVs) containing relevant biomolecules such as mRNAs, microRNAs, bioactive lipids, and signaling receptors, able to restore physiological conditions where regenerative or anti-inflammatory actions are needed. An actual advantage would come from the therapeutic use of EVs with respect to MSCs, avoiding the possible immune rejection, the lung entrapment, improving the safety, and allowing the crossing of biological barriers. A number of concerns still have to be solved regarding the mechanisms determining the beneficial effect of MSC-EVs, the possible alteration of their properties as a consequence of the isolation/purification methods, and/or the best approach for a large-scale production for clinical use. Most of the preclinical studies have been successful, reporting for MSC-EVs a protecting role in acute kidney injury following ischemia reperfusion, a potent anti-inflammatory and anti-fibrotic effects by reducing disease associated inflammation and fibrosis in lung and liver, and the modulation of both innate and adaptive immune responses in graft versus host disease (GVHD) as well as autoimmune diseases. However, the translation of MSC-EVs to the clinical stage is still at the initial phase. Herein, we discuss the therapeutic potential of an acellular product such as MSC derived EVs (MSC-EVs) in acute and chronic pathologies.

scholarly journals Matrine reduces cigarette smoke-induced airway neutrophilic inflammation by enhancing neutrophil apoptosis

2019 ◽  
Vol 133 (4) ◽  
pp. 551-564 ◽  
Author(s):  
Xuhua Yu ◽  
Huei Jiunn Seow ◽  
Hao Wang ◽  
Desiree Anthony ◽  
Steven Bozinovski ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Lung Inflammation ◽  
Therapeutic Potential ◽  
Proteolytic Enzymes ◽  
Ex Vivo ◽  
Lavage Fluid ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Neutrophilic Inflammation ◽  
Anti Inflammatory

AbstractChronic Obstructive Pulmonary Disease (COPD) is a major incurable global health burden and will become the third largest cause of death in the world by 2030. It is well established that an exaggerated inflammatory and oxidative stress response to cigarette smoke (CS) leads to, emphysema, small airway fibrosis, mucus hypersecretion, and progressive airflow limitation. Current treatments have limited efficacy in inhibiting chronic inflammation and consequently do not reverse the pathology that initiates and drives the long-term progression of disease. In particular, there are no effective therapeutics that target neutrophilic inflammation in COPD, which is known to cause tissue damage by degranulation of a suite of proteolytic enzymes including neutrophil elastase (NE). Matrine, an alkaloid compound extracted from Sophora flavescens Ait, has well known anti-inflammatory activity. Therefore, the aim of the present study was to investigate whether matrine could inhibit CS-induced lung inflammation in mice. Matrine significantly reduced CS-induced bronchoalveolar lavage fluid (BALF) neutrophilia and NE activity in mice. The reduction in BALF neutrophils in CS-exposed mice by matrine was not due to reductions in pro-neutrophil cytokines/chemokines, but rather matrine’s ability to cause apoptosis of neutrophils, which we demonstrated ex vivo. Thus, our data suggest that matrine has anti-inflammatory actions that could be of therapeutic potential in treating CS-induced lung inflammation observed in COPD.

scholarly journals Immunomodulation of Murine Chronic DSS-Induced Colitis by Tuftsin–Phosphorylcholine

2019 ◽  
Vol 9 (1) ◽  
pp. 65
Author(s):  
Dana Ben-Ami Shor ◽  
Jordan Lachnish ◽  
Tomer Bashi ◽  
Shani Dahan ◽  
Asaf Shemer ◽  
...  
Keyword(s):  
Murine Model ◽  
Lupus Erythematosus ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Activity Index ◽  
Clinical Manifestations ◽  
Host Immune System ◽  
Chronic Colitis ◽  
Mesenteric Lymph Nodes ◽  
Anti Inflammatory

Helminths or their products can immunomodulate the host immune system, and this phenomenon may be applied as the basis of new anti-inflammatory treatments. Previously, we have shown the efficacy of tuftsin–phosphorylcholine (TPC), based on a helminth product, in four animal models of autoimmune diseases: arthritis, colitis, systemic lupus erythematosus, and experimental autoimmune encephalomyelitis. We demonstrated that TPC reduced inflammatory process ex vivo in peripheral blood lymphocytes (PBLs) and in biopsies from giant-cell arteritis. In the present study, we assessed the therapeutic potential of TPC treatment on a chronic colitis murine model. C57BL/6 mice with chronic colitis were treated with TPC after the third cycle of 2% dextran sodium sulfate (DSS). Oral TPC treatment resulted in amelioration of the colitis clinical manifestations exemplified by reduced disease activity index (DAI) score, expansion of mesenteric lymph nodes (MLN) T regulatory cells (shown by Fluorescence Activated Cell Sorting (FACS)), significant reduction in the expression of pro-inflammatory cytokines (IL-1β, IL17, IL-6, TNFα), and elevation in the expression of anti-inflammatory cytokine IL-10 (shown by RT-PCR). This study demonstrated the potential immunomodulatory effects of oral administration of TPC in a chronic colitis murine model. Further clinical trials are needed in order to evaluate this novel approach for the treatment of patients with inflammatory bowel disease.

scholarly journals Effect of Otostegia persica extraction on renal injury induced by hindlimb ischemia-reperfusion: A rat model

2015 ◽  
Vol 13 ◽  
pp. 124-130 ◽  
Author(s):  
Mohammad Ashrafzadeh Takhtfooladi ◽  
Hamed Ashrafzadeh Takhtfooladi ◽  
Fariborz Moayer ◽  
Poorya Karimi ◽  
Hesam Abbasian Asl
Keyword(s):  
Rat Model ◽  
Renal Injury ◽  
Ischemia Reperfusion ◽  
Hindlimb Ischemia ◽  
Otostegia Persica

scholarly journals Potential Implications of Quercetin and its Derivatives in Cardioprotection

2020 ◽  
Vol 21 (5) ◽  
pp. 1585 ◽  
Author(s):  
Kristina Ferenczyova ◽  
Barbora Kalocayova ◽  
Monika Bartekova
Keyword(s):  
Therapeutic Potential ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Cardiac Injury ◽  
Experimental Models ◽  
Cardiac Effects ◽  
Beneficial Effects ◽  
Positive Effects ◽  
Number Of Patients ◽  
Wide Range

Quercetin (QCT) is a natural polyphenolic compound enriched in human food, mainly in vegetables, fruits and berries. QCT and its main derivatives, such as rhamnetin, rutin, hyperoside, etc., have been documented to possess many beneficial effects in the human body including their positive effects in the cardiovascular system. However, clinical implications of QCT and its derivatives are still rare. In the current paper we provide a complex picture of the most recent knowledge on the effects of QCT and its derivatives in different types of cardiac injury, mainly in ischemia-reperfusion (I/R) injury of the heart, but also in other pathologies such as anthracycline-induced cardiotoxicity or oxidative stress-induced cardiac injury, documented in in vitro and ex vivo, as well as in in vivo experimental models of cardiac injury. Moreover, we focus on cardiac effects of QCT in presence of metabolic comorbidities in addition to cardiovascular disease (CVD). Finally, we provide a short summary of clinical studies focused on cardiac effects of QCT. In general, it seems that QCT and its metabolites exert strong cardioprotective effects in a wide range of experimental models of cardiac injury, likely via their antioxidant, anti-inflammatory and molecular pathways-modulating properties; however, ageing and presence of lifestyle-related comorbidities may confound their beneficial effects in heart disease. On the other hand, due to very limited number of clinical trials focused on cardiac effects of QCT and its derivatives, clinical data are inconclusive. Thus, additional well-designed human studies including a high enough number of patients testing different concentrations of QCT are needed to reveal real therapeutic potential of QCT in CVD. Finally, several negative or controversial effects of QCT in the heart have been reported, and this should be also taken into consideration in QCT-based approaches aimed to treat CVD in humans.

Abstract 2269: Exogenous Sulfide Limits Inflammation in Response to Myocardial Ischemia - Reperfusion Injury

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Neel R Sodha ◽  
Richard T Clements ◽  
Jun Feng ◽  
Yuhong Liu ◽  
Cesario Bianchi ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
Inflammatory Cytokines ◽  
Sodium Sulfide ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Treated Group ◽  
Area At Risk ◽  
Microvascular Reactivity ◽  
Anti Inflammatory

Introduction : Hydrogen sulfide (H 2 S) is produced endogenously in response to myocardial ischemia and thought to be cardioprotective. The mechanism underlying this protection has yet to be fully elucidated, but may be related to the ability of sulfide to limit inflammation. This study investigates the cardioprotection provided by exogenous H 2 S, generated as sodium sulfide, and its potential anti-inflammatory mechanism of action. Methods : The mid-LAD coronary artery in 12 Yorkshire swine was acutely occluded for 60 min, followed by reperfusion for 120 min. Controls (6) received placebo, and treatment animals (6) received sulfide 10 min prior to reperfusion. Hemodynamic, global, and regional functional measurements were obtained. Evans blue and TTC staining identified the area at risk (AAR) and infarction. Coronary microvascular reactivity was assessed. Tissue was assayed for myeloperoxidase (MPO) activity and inflammatory cytokines. Results : Pre-I/R hemodynamics were similar between groups, whereas post-I/R mean arterial pressure (mmHg) was reduced by 28.7±5.0 in controls vs. 6.7±6.2 in treatment animals (p<0.05). +LV dP/dt (mmHg/sec) was reduced by 1325±455 in controls vs. 416±207 in treatment animals (p<0.05). Segmental shortening in the AAR was better in treatment animals. Infarct size (% of AAR) in controls was 41.0±7.8% vs. 21.2±2.5% in the treated group (p<0.05). Tissue levels of IL-6, IL-8, and TNFα (see Table ) and MPO activity decreased in the treatment group (0.0025±0.003 vs. control 0.0397±0.016 units/mg protein (p<0.05)). Treated animals demonstrated improved microvascular reactivity. Conclusions : Sodium sulfide provides significant protection in response to I/R injury, improving myocardial function, reducing infarct size, and improving coronary microvascular reactivity, potentially through its anti-inflammatory properties. Exogenous sulfide may have therapeutic utility in clinical settings in which I/R injury is encountered. Myocardial Levels of Inflammatory Cytokines

Sign in / Sign up

Export Citation Format

Share Document