Polydatin reduces cardiotoxicity of tyrosine kinase inhibitor sunitinib by decreasing pro-oxidative stress, pro-inflammatory cytokines and NLRP3 inflammasome expression.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15065-e15065
Author(s):  
Massimiliano Berretta ◽  
Vincenzo Quagliariello ◽  
Simona Buccolo ◽  
Martina Iovine ◽  
Michelino De Laurentiis ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Growth Factors ◽  
Inflammatory Cytokines ◽  
Transcriptional Activation ◽  
Nlrp3 Inflammasome ◽  
Fetal Cardiomyocytes ◽  
Cardioprotective Effects ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

e15065 Background: : Polydatin has anticancer and anti-inflammatory properties, however no studies investigated on its putative cardioprotective effects against anticancer therapies. Sunitinib, a recently-approved, multi-targeted tyrosine kinases inhibitor, prolongs survival in patients with metastatic renal cell carcinoma and gastrointestinal stromal tumors, however a dose related cardiotoxicity was well described. We investigated on the reduction of cytokines and growth factors of polydatin resulting in putative cardioprotective effects. Methods: Human fetal cardiomyocytes were untreated (control) or treated for 48 h with polydatin (50,100,200 and 400 µM) or sunitinib (5,10,25 and 50 µM) alone or combined to polydatin. After the incubation period, we performed the following tests: determination of cell viability, through analysis of mitochondrial dehydrogenase activity, study of lipid peroxidation (quantifying cellular malondialdehyde and 4-hydroxynonenal), intracellular Ca2+ homeostasis. Moreover, pro-inflammatory studied were also performed (activation of NLRP3 inflammasome; expression of TLR4/MyD88; mTORC1 Fox01/3a; transcriptional activation of p65/NF-κB and secretion of cytokines involved in cardiotoxicity (Interleukins 1β, 8, 6). Results: Exposure of adult cardiomyocytes to polydatin combined to plasma-relevant concentrations of sunitinib reduces significantly intracellular reactive oxygen species, lipid peroxidation and cytochrome c release from mitochondria leading to a reduction in cell death compared to cells exposed to sunitinib alone. Polydatin reduces expression of pro-inflammatory cytokines and growth factors involved in myocardial damages and down-regulates the signaling pathway of NLRP3 inflammasome and NF-κB, increasing cellular resistance to sunitinib-mediated damages. Conclusions: Data of the present study, although in vitro, indicate that polydatin, besides reducing oxidative stress, has cardioprotective and anti-inflammatory properties, thus indicating one the mechanism(s) by which this metabolite of resveratrol might decrease sunitinib-mediated cardiotoxicity.

scholarly journals Titán-dioxid-nanopálcikák tüdőre kifejtett hatásának állatkísérletes vizsgálata szubakut patkánymodellben

2019 ◽  
Vol 160 (2) ◽  
pp. 57-66 ◽  
Author(s):  
Tamara Horváth ◽  
András Papp ◽  
Mónika Kiricsi ◽  
Nóra Igaz ◽  
Vivien Trenka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Electron Microscopy ◽  
Lipid Peroxidation ◽  
Lymph Nodes ◽  
Inflammatory Cytokines ◽  
Lung Tissue ◽  
Light And Electron Microscopy ◽  
Biochemical Methods ◽  
Ti Content ◽  
Pro Inflammatory Cytokines

Abstract: Introduction: The development of nanotechnology increases the risk of occupational and population-level exposure to nanoparticles nowadays. However, scientifically based knowledge relating to the toxicity of heavy metal nanoparticles and potential health damage is insufficient. Aim: Investigation of lung tissue damage induced by titanium dioxide (TiO2) nanorods in subacute intratracheal instillation by morphological, chemical and biochemical methods in rat model. Method: General toxicity (changes of body and organ weights), local acute and chronic cellular toxicity (in alveolar spaces and epithelium, in hilar lymph nodes) and oxidative stress were examined using light and electron microscopy, and biochemical methods (reactive oxygen species, lipid peroxidation, expression of pro-inflammatory cytokines). Results: No dose- and time-dependent alteration was found in the body weight of the treated groups; but the mass and Ti content of lungs increased with dose. Light and electron microscopy of the lung tissue verified the presence of nanoparticles, free in the alveolar space and within phagosomes of macrophages not attached to alveolar epithelium. Chronification of local acute alveolitis was supported by dose-dependent increase of macrophage count in the alveolar region, oedema and thickening of interstitium, and increased expression of certain pro-inflammatory cytokines (interleukin-1a, LIX, L-selectin, vascular endothelial growth factor). Oxidative stress and lipid peroxidation increased substantially in the treated rats’ lungs, and correlation was found between Ti content and lipid peroxidation. Insufficiency of the alveolar epithelial and capillary endothelial barrier was indicated by nanoparticle-laden phagocytes in hilar lymph nodes, suggesting nanoparticles reaching systemic circulation and distant organs, inducing systemic acute inflammation. Conclusion: TiO2 nanoparticles, reaching lower airways, may be etiological factors in the causation or aggravation of pulmonary diseases with acute and chronic airways inflammation and/or progressive fibrosis and obstruction (e.g., chronic obstructive pulmonary disease or asthma). Autophagy and damaged immune response (lymphocytic activity) may have here a role. Orv Hetil. 2019; 160(2): 57–66.

scholarly journals Celecoxib Decrease Seizures Susceptibility in a Rat Model of Inflammation by Inhibiting HMGB1 Translocation

2021 ◽  
Vol 14 (4) ◽  
pp. 380
Author(s):  
Hadeel Alsaegh ◽  
Hala Eweis ◽  
Fatemah Kamal ◽  
Aziza Alrafiah
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Control Group ◽  
Protective Effects ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Inflammatory Models ◽  
Anti Inflammatory ◽  
Lung And Kidney ◽  
Pro Inflammatory Cytokines

The risk of developing epilepsy is strongly linked to peripheral inflammatory disorders in humans. High-mobility group box protein 1 (HMGB1) has the most focus for being a suspect in this scenario. The current study aimed to detect the celecoxib effect, an anti-inflammatory drug, on decreasing seizure susceptibility and organ damage in lipopolysaccharides (LPS)/pilocarpine (PILO) pretreated Wistar rats. Rats were divided into 6 groups (8 each): group 1 (control), group 2 (PILO), group 3 (PILO+LPS), group 4 (PILO+LPS+(VPA) Valproic acid), group 5 (PILO+LPS+Celecoxib), and group 6 (PILO+LPS+VPA+Celecoxib). LPS was used to induce sepsis and PILO to induce seizures. Oxidative stress markers, pro-inflammatory cytokines, and HMGB1 levels in serum and brain homogenate were evaluated. Histopathological studies were conducted on the hippocampus, liver, lung, and kidney. Treatment with celecoxib either alone or in combination with VPA significantly reduced Racine score and delays latency to generalized tonic-clonic seizures onset with a significant decrease in hippocampal levels of pro-inflammatory cytokines, oxidative stress markers, and increase in reduced glutathione. In addition, celecoxib treatment either alone or in combination with VPA suppressed HMGB1translocation into peripheral circulation more than treatment with VPA alone. Furthermore, hippocampus, liver, lung, and kidney histopathological changes were improved in contrast to other epileptic groups. Celecoxib either alone or combined with VPA has antiepileptic and multiorgan protective effects on acute seizures and inflammatory models induced by PILO with LPS. It decreased histopathological findings, oxidative, and inflammatory effects induced by VPA and LPS. This might be due to its anti-oxidative, anti-inflammatory and anti-HMGB1 mediated effects.

scholarly journals In vivo, Extract from Withania somnifera Root Ameliorates Arthritis via Regulation of Key Immune Mediators of Inflammation in Experimental Model of Arthritis

2019 ◽  
Vol 18 (1) ◽  
pp. 55-70 ◽  
Author(s):  
Mahmood Ahmad Khan ◽  
Rafat Sultana Ahmed ◽  
Nilesh Chandra ◽  
Vinod Kumar Arora ◽  
Athar Ali
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Inflammatory Cytokines ◽  
Withania Somnifera ◽  
Antioxidant Defense System ◽  
Inflammatory Activity ◽  
Mediators Of Inflammation ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Background: Rheumatoid Arthritis (RA) is a devastating disease characterized by continual addition of leukocytes and T cells within the articular cavity causing inflammation and cartilage destruction. Withania somnifera is one of the most precious medicinal herbs, reported to have antioxidant, anti‐inflammatory, and immunomodulatory properties. </P><P> Objective: The purpose of this study was to evaluate anti-inflammatory activity of aqueous extract of Withania somnifera roots (WSAq) in Collagen Induced Arthritic (CIA) rats. </P><P> Methods: To achieve this, we assessed the level of inflammatory cytokines such as Tumor Necrosis Factor (TNF)-&#945;, IL-1&#946;, IL-6 and IL-10 in CIA rats. Further, transcription factor, oxidative stress parameters and CD+8 expressions were also analyzed in CIA rats. </P><P> Results: Arthritic rats showed a greater increase in the levels of pro inflammatory cytokines such as TNF-&#945;, IL-1&#946;, IL-6, transcription factor NF-&#954;B and a decrease in IL-10 concentration than controls rats. Oral administration of WSAq at a dose of 300mg/kg.wt. (WSAq300) appreciably attenuated the production of these pro inflammatory cytokines. This anti-inflammatory activity of WSAq300 might be partly mediated through an increase in the secretion of IL-10 and inhibition of NF-&#954;B activity. Further, arthritic rats also show increased oxidative stress as compared to control rats. This increased oxidative stress in the arthritic rats appears to be the outcome of both an activated pro-oxidant and a poor antioxidant defense system. Treatment with WSAq300 strongly ameliorates all these ROS parameters significantly to near normal. Additional, metalloproteinase MMP-8 levels were also measured and found to be increased in CIA rats, which after treatment with WSAq300 came down to near normal. </P><P> Conclusion: From the above results, it can be concluded that the use of WSAq300 may be a valuable supplement which can improve human arthritis.

scholarly journals Mulberry Leaf Extract Alleviates Staphylococcus Aureus-Induced Conjunctivitis in Rabbits via Downregulation of NLRP3 Inflammaome and Upregulation of the Nrf2 System and Suppression of Pro-Inflammatory Cytokines

2021 ◽  
Author(s):  
Chen Ying ◽  
Linglin Lai ◽  
Zhentao Mo ◽  
Ennian Leng ◽  
Yueyue Zhang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Inflammatory Cytokines ◽  
Nlrp3 Inflammasome ◽  
Leaf Extract ◽  
Eye Drops ◽  
Dependent Manner ◽  
Mulberry Leaf ◽  
Mulberry Leaf Extract ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Abstract Mulberry leaves are widely used in traditional Chinese medicine for their antioxidant, anti-inflammatory, antibacterial, antiobesity, antidiabetic, antiatherosclerotic, and anticancer properties. The current study aimed to investigate the effect of mulberry leaf extract (MLE) on Staphylococcus aureus (S. aureus)-induced conjunctivitis (5 × 109 CFU, 0.5 mL/eye) in a rabbit model. Rabbits were treated with MLE (5 mL/kg·d-1 and 10 mL/kg·d-1), 0.9% saline, or pearl bright eye drops (PBE) for 5 days. The results showed that MLE treatment significantly reduced the clinical sign scores of conjunctivitis, alleviated clinical signs, and decreased bacterial load and histological damage in a time- and dose-dependent manner compared to that in the conjunctivitis control group. The antibacterial and anti-inflammatory activities of MLE (10 mL/kg·d-1) were equal to or greater than those of the positive control drug PBE. In addition, MLE significantly decreased the levels of pro-inflammatory cytokines, downregulated the NOD-like receptor leucine-rich pyrin domain-containing protein 3 (NLRP3) inflammasome, and upregulated the nuclear factor erythroid 2-related factor 2 (Nrf2) system. Overall, MLE is effective in alleviating S. aureus-induced conjunctivitis in rabbits and this mechanism is associated with the inhibition of the NLRP3 inflammasome and activation of the Nrf2 system to regulate pro-inflammatory signaling.

scholarly journals Antioxidant, Anti-inflammatory, and Anti-arthritic Effect of Thymoquinone-rich Black Cumin (Nigella sativa) oil (BlaQmax®) on Adjuvant-induced Arthritis

2021 ◽  
Vol 10 (1) ◽  
pp. 52
Author(s):  
M. Ratheesh ◽  
Jose P. Svenia ◽  
Saji Sangeeth ◽  
S. Sheethal ◽  
Rajan Sony ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Inflammatory Cytokines ◽  
Nigella Sativa ◽  
Autoimmune Disorder ◽  
Gene Expressions ◽  
Black Cumin ◽  
Nigella Sativa Oil ◽  
Adjuvant Induced Arthritis ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Rheumatoid Arthritis (RA) is a complex autoimmune disorder involving chronic and persistent inflammation, principally influencing the synovial joints which further prompting the obliteration of articular cartilage. Although black cumin (Nigella sativa) oil has already studied for its anti-arthritic properties, the current study was focused on the comparative evaluation of the antioxidant and anti-inflammatory properties of a thymoquinone (TQ)-rich (5% w/v) black cumin oil (BQ) with the commonly available standard black cumin oil (BM) containing 0.4% (w/v) TQ, and subsequent investigation on the potential application of BQ in the management of RA. Adjuvant-induced arthritis (AA) was instigated by a single intradermal infusion of 0.1 mL of Complete Freund&#39;s adjuvant (CFA) on the paw of adult Wistar rats. Based on the primary dose-response study using the carrageenan-induced paw edema model, 50 mg/kg b.wt. of BQ was employed for the treatment. The endogenous antioxidants (SOD, Catalase, GPx, and GSH), pro-inflammatory cytokines (COX-2, Nitrate, iNOS, TNF-&alpha;, IL-6), lipid peroxidation, and histopathology were evaluated to monitor the influence of BQ in AA rats. Adjuvant-induced animals showed a critical downregulation in antioxidant status with elevated levels of pro-inflammatory cytokines and lipid peroxidation. But, the treatment with BQ significantly reversed the antioxidant and inflammatory markers with downregulation of the pro-inflammatory gene expressions. Histopathology showed a significant reduction in the massive cell infiltration and epidermal edema of the paw tissue in AA rats when administered with BQ and indicated its potential effect to alleviate RA conditions in experimental rats.

scholarly journals Immunomodulatory and antimicrobial non-mulberry Antheraea mylitta silk fibroin accelerates in vitro fibroblast repair and regeneration by protecting oxidative stress

RSC Advances ◽  
2021 ◽  
Vol 11 (31) ◽  
pp. 19265-19282
Author(s):  
Sohini Sen ◽  
Shaunak Ghosh ◽  
Sayantan De ◽  
Piyali Basak ◽  
Praveen Maurye ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Silk Fibroin ◽  
Reverse Order ◽  
Antheraea Mylitta ◽  
Ki 67 ◽  
Cellular Regeneration ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Initially SF accelerated pro-inflammatory cytokines, restricted anti-inflammatory cytokines; later it regulated in reverse order. SF potentially eradicated ROS and promoted Ki-67 cellular regeneration whereas pristine PU could not.

scholarly journals Cytokine response during non-cerebral and cerebral malaria: evidence of a failure to control inflammation as a cause of death in African adults

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1965 ◽  
Author(s):  
Yakhya Dieye ◽  
Babacar Mbengue ◽  
Shobha Dagamajalu ◽  
Mouhamadou Mansour Fall ◽  
Mun Fai Loke ◽  
...  
Keyword(s):  
Growth Factors ◽  
Cerebral Malaria ◽  
Inflammatory Cytokines ◽  
Serum Levels ◽  
Organ Damage ◽  
Inflammatory Biomarkers ◽  
Immune Mediators ◽  
Anti Inflammatory ◽  
Almost All ◽  
Pro Inflammatory Cytokines

Background.With 214 million cases and 438,000 deaths in 2015, malaria remains one of the deadliest infectious diseases in tropical countries. Several species of the protozoanPlasmodiumcause malaria. However, almost all the fatalities are due toPlasmodium falciparum, a species responsible for the severest cases including cerebral malaria. Immune response toPlasmodiumfalciparum infection is mediated by the production of pro-inflammatory cytokines, chemokines and growth factors whose actions are crucial for the control of the parasites. Following this response, the induction of anti-inflammatory immune mediators downregulates the inflammation thus preventing its adverse effects such as damages to various organs and death.Methods.We performed a retrospective, nonprobability sampling study using clinical data and sera samples from patients, mainly adults, suffering of non-cerebral or cerebral malaria in Dakar, Sénégal. Healthy individuals residing in the same area were included as controls. We measured the serum levels of 29 biomarkers including growth factors, chemokines, inflammatory and anti-inflammatory cytokines.Results.We found an induction of both pro- and anti-inflammatory immune mediators during malaria. The levels of pro-inflammatory biomarkers were higher in the cerebral malaria than in the non-cerebral malaria patients. In contrast, the concentrations of anti-inflammatory cytokines were comparable in these two groups or lower in CM patients. Additionally, four pro-inflammatory biomarkers were significantly increased in the deceased of cerebral malaria compared to the survivors. Regarding organ damage, kidney failure was significantly associated with death in adults suffering of cerebral malaria.Conclusions.Our results suggest that a poorly controlled inflammatory response determines a bad outcome in African adults suffering of cerebral malaria.

scholarly journals Polydatin Reduces Cardiotoxicity and Enhances the Anticancer Effects of Sunitinib by Decreasing Pro-Oxidative Stress, Pro-Inflammatory Cytokines, and NLRP3 Inflammasome Expression

2021 ◽  
Vol 11 ◽  
Author(s):  
Vincenzo Quagliariello ◽  
Massimiliano Berretta ◽  
Simona Buccolo ◽  
Martina Iovine ◽  
Andrea Paccone ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Inflammatory Cytokines ◽  
Nlrp3 Inflammasome ◽  
Renal Cell ◽  
Renal Tumors ◽  
H9c2 Cell ◽  
Cytokines And Chemokines ◽  
Pro Inflammatory Cytokines

Renal cell carcinoma (RCC) represents the main renal tumors and are highly metastatic. Sunitinib, a recently-approved, multi-targeted Tyrosine Kinases Inhibitor (TKi), prolongs survival in patients with metastatic renal cell carcinoma and gastrointestinal stromal tumors, however a dose related cardiotoxicity was well described. Polydatin (3,4’,5-trihydroxystilbene-3-β-d-glucoside) is a monocrystalline compound isolated from Polygonum cuspidatum with consolidated anti-oxidant and anti-inflammatory properties, however no studies investigated on its putative cardioprotective and chemosensitizing properties during incubation with sunitinib. We investigated on the effects of polydatin on the oxidative stress, NLRP3 inflammasome and Myd88 expression, highlighting on the production of cytokines and chemokines (IL-1β, IL-6, IL-8, CXCL-12 and TGF-β) during treatment with sunitinib. Exposure of cardiomyocytes and cardiomyoblasts (AC-16 and H9C2 cell lines) and human renal adenocarcinoma cells (769‐P and A498) to polydatin combined to plasma-relevant concentrations of sunitinib reduces significantly iROS, MDA and LTB4 compared to only sunitinib-treated cells (P&lt;0.001). In renal cancer cells and cardiomyocytes polydatin reduces expression of pro-inflammatory cytokines and chemokines involved in myocardial damages and chemoresistance and down-regulates the signaling pathway of NLRP3 inflammasome, MyD88 and NF-κB. Data of the present study, although in vitro, indicate that polydatin, besides reducing oxidative stress, reduces key chemokines involved in cancer cell survival, chemoresistance and cardiac damages of sunitinib through downregulation of NLRP3-MyD88 pathway, applying as a potential nutraceutical agent in preclinical studies of preventive cardio-oncology.

scholarly journals Ellagic Acid Prevents Dopamine Neuron Degeneration from Oxidative Stress and Neuroinflammation in MPTP Model of Parkinson’s Disease

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1519
Author(s):  
Mustafa T. Ardah ◽  
Greeshma Bharathan ◽  
Tohru Kitada ◽  
M. Emdadul Haque
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Lipid Peroxidation ◽  
Parkinson's Disease ◽  
Body Weight ◽  
Dopamine Transporter ◽  
Inflammatory Cytokines ◽  
Mptp Administration ◽  
Cox 2 ◽  
Pro Inflammatory Cytokines

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases and is characterized by progressive dopaminergic neurodegeneration in the substantia nigra pars compacta area. In the present study, treatment of EA for 1 week at a dose of 10 mg/kg body weight prior to MPTP (25 mg/kg body weight) was carried out. MPTP administration caused oxidative stress, as evidenced by decreased activities of superoxide dismutase and catalase, and the depletion of reduced glutathione with a concomitant rise in the lipid peroxidation product, malondialdehyde. It also significantly increased the pro-inflammatory cytokines and elevated the inflammatory mediators like cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the striatum. Immunohistochemical analysis revealed a loss of dopamine neurons in the SNc area and a decrease in dopamine transporter in the striatum following MPTP administration. However, treatment with EA prior to MPTP injection significantly rescued the dopaminergic neurons and dopamine transporter. EA treatment further restored antioxidant enzymes, prevented the depletion of glutathione and inhibited lipid peroxidation, in addition to the attenuation of pro-inflammatory cytokines. EA also reduced the levels of COX-2 and iNOS. The findings of the present study demonstrate that EA protects against MPTP-induced PD and the observed neuroprotective effects can be attributed to its potent antioxidant and anti-inflammatory properties.

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