The Protective Effect of New Carnosine-Hyaluronic Acid Conjugate on the Inflammation and Cartilage Degradation in the Experimental Model of Osteoarthritis

Osteoarthritis (OA) is a disease that currently has no cure. There are numerous studies showing that carnosine and hyaluronic acid (HA) have a positive pharmacological action during joint inflammation. For this reason, the goal of this research was to discover the protective effect of a new carnosine conjugate with hyaluronic acid (FidHycarn) on the inflammatory response and on the cartilage degradation in an in vivo experimental model of OA. This model was induced by a single intra-articular (i.ar.) injection of 25 µL of normal saline with 1 mg of monosodium iodoacetate solution (MIA) in the knee joint of rats. MIA injection caused histological alterations and degradation of the cartilage, as well as behavioral changes. Oral treatment with FidHycarn ameliorated the macroscopic signs, improved thermal hyperalgesia and the weight distribution of the hind paw, and decreased histological and radiographic alterations. The oxidative damage was analyzed by evaluating the levels of nitrotyrosine and inducible nitric oxide synthase (iNOS) that were significantly reduced in FidHycarn rats. Moreover, the levels of pro-inflammatory cytokines and chemokines were also significantly reduced by FidHycarn. Therefore, for the first time, the effectiveness of oral administration of FidHycarn has been demonstrated in an osteoarthritis model. In conclusion, the new FidHycarn could represent an interesting therapeutic strategy to combat osteoarthritis.

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Protective Effect of New Formulation of Carnosine+Hyaluronic Acid on the Inflammation and Cartilage Degradation in the Experimental Model of Osteoarthritis

10.20944/preprints202001.0105.v1 ◽

2020 ◽

Author(s):

Rosalba Siracusa ◽

Daniela Impellizzeri ◽

Marika Cordaro ◽

Alessio F. Peritore ◽

Enrico Gugliandolo ◽

...

Keyword(s):

Hyaluronic Acid ◽

Protective Effect ◽

Experimental Model ◽

Oral Treatment ◽

Thermal Hyperalgesia ◽

Joint Inflammation ◽

Pharmacological Action ◽

Cartilage Degradation ◽

New Formulation

Osteoarthritis (OA) is a disease that currently has no cure. There are numerous studies showing that carnosine and hyaluronic acid (HA) have a positive pharmacological action during joint inflammation. For this reason, the goal of this research was to discover the protective effect of a new HA+Carnosine formulation (FidHycarn) on the inflammatory response and on the cartilage degradation in in vivo experimental model of OA. This model was induced by a single intra-articular (i.ar.) injection of 25µl normal saline having 1mg of monosodium iodoacetate solution (MIA) in the knee joint. MIA injection caused histological alterations and degradation of cartilage as well as behavioral changes. Oral treatment with FidHycarn ameliorated the macroscopic signs, improved thermal hyperalgesia and weight distribution of hind paw as well as decreased histological and radiographic alterations. The oxidative damage was analyzed by evaluating the levels of nitrotyrosine and inducible nitric oxide synthase (iNOS) that were significantly reduced in FidHycarn rats. Moreover, the levels of pro-inflammatory cytokines and chemokines were also significantly reduced by FidHycarn. However, interestingly, in more cases, the effects of FidHycarn were not statistically different to Naproxen used as positive control. Thus, the new formulation containing Carnosine and HA could represent an interesting therapeutic strategy to combat osteoarthritis.

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Nitroglycerine limits infarct size through S-nitrosation of cyclophilin D: a novel mechanism for an old drug

Cardiovascular Research ◽

10.1093/cvr/cvy222 ◽

2018 ◽

Vol 115 (3) ◽

pp. 625-636 ◽

Cited By ~ 13

Author(s):

Sofia-Iris Bibli ◽

Andreas Papapetropoulos ◽

Efstathios K Iliodromitis ◽

Andreas Daiber ◽

Voahanginirina Randriamboavonjy ◽

...

Keyword(s):

Protective Effect ◽

Infarct Size ◽

Knockout Mice ◽

Low Dose ◽

Myocardial Infarct ◽

Pharmacological Action ◽

Myocardial Infarct Size ◽

Cyclophilin D ◽

Cardioprotective Effects

Abstract Aims Nitroglycerine (NTG) given prior to an ischaemic insult exerts cardioprotective effects. However, whether administration of an acute low dose of NTG in a clinically relevant manner following an ischaemic episode limits infarct size, has not yet been explored. Methods and results Adult mice were subjected to acute myocardial infarction in vivo and then treated with vehicle or low-dose NTG prior to reperfusion. This treatment regimen minimized myocardial infarct size without affecting haemodynamic parameters but the protective effect was absent in mice rendered tolerant to the drug. Mechanistically, NTG was shown to nitrosate and inhibit cyclophilin D (CypD), and NTG administration failed to limit infarct size in CypD knockout mice. Additional experiments revealed lack of the NTG protective effect following genetic (knockout mice) or pharmacological inhibition (L-NAME treatment) of the endothelial nitric oxide synthase (eNOS). The protective effect of NTG was attributed to preservation of the eNOS dimer. Moreover, NTG retained its cardioprotective effects in a model of endothelial dysfunction (ApoE knockout) by preserving CypD nitrosation. Human ischaemic heart biopsies revealed reduced eNOS activity and exhibited reduced CypD nitrosation. Conclusion Low-dose NTG given prior to reperfusion reduces myocardial infarct size by preserving eNOS function, and the subsequent eNOS-dependent S-nitrosation of CypD, inhibiting cardiomyocyte necrosis. This novel pharmacological action of NTG warrants confirmation in clinical studies, although our data in human biopsies provide promising preliminary results.

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Hyaluronan-Loaded Liposomal Dexamethasone– Diclofenac Nanoparticles for Local Osteoarthritis Treatment

International Journal of Molecular Sciences ◽

10.3390/ijms22020665 ◽

2021 ◽

Vol 22 (2) ◽

pp. 665

Author(s):

Ming-Cheng Chang ◽

Ping-Fang Chiang ◽

Yu-Jen Kuo ◽

Cheng-Liang Peng ◽

Kuan-Yin Chen ◽

...

Keyword(s):

Hyaluronic Acid ◽

Joint Pain ◽

Articular Chondrocytes ◽

Imaging System ◽

Treatment Strategies ◽

Entrapment Efficiency ◽

Joint Inflammation ◽

Time Span ◽

Live Animal

Osteoarthritis (OA) remains one of the common degenerative joint diseases and a major cause of pain and disability in older adult individuals. Oral administration of non-steroidal anti-inflammatory drugs (NSAIDs) (such as diclofenac, DIC) or intra-articular injected gluco-corticosteroids (such as dexamethasone, DEX) were the conventional treatment strategies for OA to reduce joint pain. Current limitations for both drugs including severe adverse effects with risks of toxicity were noted. The aim of the present study was to generate a novel OA treatment formulation hyaluronic acid (HA)-Liposomal (Lipo)-DIC/DEX to combat joint pain. The formulation was prepared by constructing DIC with DEX-loaded nanostructured lipid carriers Lipo-DIC/DEX mixed with hyaluronic acid (HA) for prolonged OA application. The prepared Lipo-DIC/DEX nanoparticles revealed the size as 103.6 ± 0.3 nm on average, zeta potential as −22.3 ± 4.6 mV, the entrapment efficiency of 90.5 ± 5.6%, and the DIC and DEX content was 22.5 ± 4.1 and 2.5 ± 0.6%, respectively. Evidence indicated that HA-Lipo-DIC/DEX could reach the effective working concentration in 4 h and sustained the drug-releasing time for at least 168 h. No significant toxicities but increased cell numbers were observed when HA-Lipo-DIC/DEX co-cultured with articular chondrocytes cells. Using live-animal In vivo imaging system (IVIS), intra-articular injection of each HA-Lipo-DIC/DEX sufficed to reduce knee joint inflammation in OA mice over a time span of four weeks. Single-dose injection could reduce the inflammation volume down to 77.5 ± 5.1% from initial over that time span. Our results provided the novel drug-releasing formulation with safety and efficiency which could be a promising system for osteoarthritis pain control.

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Inosine reduces inflammation and improves survival in a murine model of colitis

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00060.2002 ◽

2003 ◽

Vol 284 (1) ◽

pp. G138-G144 ◽

Cited By ~ 53

Author(s):

J. G. Mabley ◽

P. Pacher ◽

L. Liaudet ◽

F. G. Soriano ◽

G. Haskó ◽

...

Keyword(s):

Lipid Peroxidation ◽

Inflammatory Cell ◽

Dextran Sulfate ◽

Oral Treatment ◽

Inflammatory Cell Infiltration ◽

Cell Infiltration ◽

Cytokines And Chemokines ◽

Naturally Occurring

Inosine, a naturally occurring purine formed from the breakdown of adenosine, has recently been shown to exert powerful anti-inflammatory effects both in vivo and in vitro. This study evaluated inosine as a potential therapy for colitis. Colitis was induced in mice by the administration of dextran sulfate sodium (DSS). Oral treatment with inosine was begun either before the onset of colitis or as a posttreatment once colitis was established. Evaluation of colon damage and inflammation was determined grossly (body wt, rectal bleeding), histologically, and biochemically (colon levels of MPO, MDA, and cytokines). DSS-induced colitis significantly increased inflammatory cell infiltration into the colon. DSS-induced colitis also increased colon levels of lipid peroxidation, cytokines, and chemokines. Inosine protected the colon from DSS-induced inflammatory cell infiltration and lipid peroxidation. Inosine also partially reduced these parameters in an experimental model of established colitis. Thus inosine treatment may be a potential therapy in colitis.

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P1220 Phytoestrogens do not abolish the protective effect of preconditioning in vivo

European Heart Journal ◽

10.1016/s0195-668x(03)94512-x ◽

2003 ◽

Vol 24 (5) ◽

pp. 230

Author(s):

E SBAROUNI

Keyword(s):

Protective Effect

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Hepato- and Nephroprotective Effects of the Polyphenol Concentrate From Cabernet Sauvignon Grape Varieties Cultivated in Kazakhstan in the Experimental Model Of CCL4-Induced Toxicity

INTERNATIONAL JOURNAL OF TOXICOLOGICAL AND PHARMACOLOGICAL RESEARCH ◽

10.25258/ijtpr.v9i03.9068 ◽

2017 ◽

Vol 9 (03) ◽

Author(s):

Nurgozhin T. ◽

Sergazy S. H. ◽

Adilgozhina G. ◽

Gulyayev A. ◽

Shulgau Z. ◽

...

Keyword(s):

Carbon Tetrachloride ◽

Experimental Model ◽

Lethal Dose ◽

Radical Scavenging ◽

Cabernet Sauvignon ◽

Intragastric Administration ◽

Liver And Kidney ◽

Antioxidant Stress

Objective:This study investigates the hepatoprotective effect and the antioxidant role of polyphenol concentrate in the experimental model of carbon tetrachloride (CCl4) induced toxicity. Methods: Antioxidant activity of Cabernet Sauvignon grape polyphenol were evaluated by radical scavenging of 1,1-diphenyl-2-picryl hydrazyl radical (DPPH), 2,2’-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS.+). In addition, the effects of polyphenol concentrate on the survival of Wistar rats in the toxicity model, was also investigated. The polyphenol concentrate was administered for 5 five days prior to injection of carbon tetrachloride in a sub-lethal dose of 300 mg/kg of animal body weight in order to perform histological examinations of the liver and kidney, and detect the levels of AST, ALT and bilirubin. Results: Administration of polyphenol concentrate increased animal survival in the experimental model. Moreover, the intragastric administration of polyphenol concentrate prior to the initiation of the experimental model of toxicity, which was caused by a sub-lethal CCl4 dose, reduced morphological injuries in the liver and kidney, decreased the AST and ALT levels of the blood serum. Discussion and conclusion: Our data demonstrate that polyphenol concentrate possesses an antioxidant potential both in vitro and in vivo by reducing antioxidant stress that was caused by CCl4 administration into rats.

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Protective Effect of Boswellic Resin Against Memory Loss and Alzheimer’s Induced by Aluminum Tetrachloride and D-Galactose (Experimental study in Mice)

Phytothérapie ◽

10.3166/phyto-2020-0222 ◽

2020 ◽

Author(s):

K. Zerrouki ◽

N. Djebli ◽

L. Gadouche ◽

I. Erdogan Orhan ◽

F. SezerSenol Deniz ◽

...

Keyword(s):

Chemical Composition ◽

Protective Effect ◽

Cell Damage ◽

Memory Loss ◽

Control Group ◽

Total Extract ◽

Swiss Mice ◽

Octyl Acetate

Nowadays, because of the industrialization, a lot of contaminant were available ; the consequences of this availability are apparition of diseases including neurodegeneration. Neurodegenerative diseases of the human brain comprise a variety of disorders that affect an increasing percentage of the population. This study is based on the effect of the Boswellic resin, which is from a medicinal plant and known for its antioxidant effects on nerve cell damage. The objective of this work was to evaluate the in vitro and in vivo effects of the Boswellic resin on anticholinesterase activity and Alzheimer’s disease (AD) induced by D-galactose and aluminum tetrachloride in Swiss mice. Chemical composition of the resin essential oil was identified by the CG-MS analysis. The antioxidant activity was also assessed by the DMPD and metal chelation methods. In order to understand the mechanism of memory improvement, the acetylcholinesterase, AChE, and butyrylcholinesterase, BChE, inhibitory assays were performed. In vivo part of the study was achieved on Swiss mice divided into four groups: control, AD model, treated AD, and treated control group. The identification of chemical composition by CG-MS reach the 89.67% of the total extract compounds presented some very important molecules (p-Cymene, n-Octyl acetate, α-Pinene…). The present study proves that Boswellic resin improves memory and learning in treated Alzheimer’s group, modulates the oxidative stress and be involved in the protective effect against amyloid deposition and neurodegeneration, and stimulates the immune system in mice’s brain.

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