scholarly journals Quinacrine Ameliorates Cisplatin-Induced Renal Toxicity via Modulation of Sirtuin-1 Pathway

2021 ◽  
Vol 22 (19) ◽  
pp. 10660
Author(s):  
Nada F. Abo El-Magd ◽  
Hasnaa Ali Ebrahim ◽  
Mohamed El-Sherbiny ◽  
Nada H. Eisa
Keyword(s):  
Renal Toxicity ◽  
Weight Ratio ◽  
Renal Tissue ◽  
Sirtuin 1 ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Tnf Α ◽  
Ameliorative Effect ◽  
Induced Apoptosis ◽  
Factor Α

Renal toxicity is a serious side effect that hinders the use of cisplatin, a commonly used and effective chemotherapeutic agent. Meanwhile, quinacrine is an FDA approved drug that has been stated for its anti-inflammatory effect. Thus, we investigated the ameliorative effect of quinacrine against cisplatin-induced renal toxicity. Single intraperitoneal (i.p.) 10 mg/kg cisplatin administration induced renal injury in rats. Our results showed that 10 mg/kg/day quinacrine decreased the mortality rate of rats from 46.15% (cisplatin group) to 12.5%, and significantly decreased renal tissue fibrosis, relative kidney to body weight ratio, serum creatinine and urea levels compared with the cisplatin group. Indeed, quinacrine significantly decreased renal malondialdehyde concentration and increased renal total antioxidant capacity, compared with the cisplatin group. Furthermore, quinacrine caused significant upregulation of renal sirtuin-1 (SIRT-1) with significant downregulation of intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-α (TNF-α). Moreover, quinacrine significantly blocked cisplatin-induced apoptosis, which was made evident by downregulating renal apoptotic proteins (BAX and p53) and upregulating the renal anti-apoptotic protein BCL2, compared with the cisplatin group. In conclusion, this study demonstrates, for the first time, that quinacrine alleviates cisplatin-induced renal toxicity via upregulating SIRT-1, downregulating inflammatory markers (ICAM-1 and TNF-α), reducing oxidative stress, and inhibiting apoptosis.

The Role of Oxidative Stress, Inflammation, and Advanced Glycation End Product in Skin Manifestations of Diabetes Mellitus

2021 ◽  
Vol 17 ◽  
Author(s):  
Lili Legiawati
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Skin Disorders ◽  
Intercellular Adhesion Molecule 1 ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
High Level ◽  
Factor Α

: Diabetes mellitus is a metabolic disorder caused by an increase in insulin resistance, a decrease in insulin production, or both of them, resulting in a high level of blood glucose or hyperglycemia. An uncontrolled state of DM may cause complications, namely skin disorder. One or more skin disorders are found amongst 74% of T2DM patients, with the highest percentage is dry skin (47%), followed by infection (10%), diabetic hand (5%), hair loss and diabetic dermopathy (each 4%). In DM, the state of hyperglycemia and production of advanced glycaemic end-products (AGEs) profoundly impact skin changes. In the pathological pathway, AGEs induce oxidative stress and inflammation. Nonetheless, AGEs level is higher in T2DM patients compared to non-T2DM people. This is caused by hyperglycemia and oxidative stress. Binding between AGEs and receptor of AGEs (RAGE) promotes pathway of oxidative stress and inflammation cascade via mitogen-activated protein kinases (MAPK), nuclear factor-k-light-chain-enhancer of activated β cells (NF-kβ), interleukin- 6 (IL-6), tumor necrosis factor-α (TNF-α), expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 2 (VCAM-2) pathway which furtherly effectuates DM complication including skin disorders.

scholarly journals Resveratrol prevents TNF-α-induced VCAM-1 and ICAM-1 upregulation in endothelial progenitor cells via reduction of NF-κB activation

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052094513
Author(s):  
Yefei Zhang ◽  
Huahua Liu ◽  
Weiliang Tang ◽  
Qiongya Qiu ◽  
Jiahao Peng
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Adhesion Molecule ◽  
Nuclear Factor Κb ◽  
Intercellular Adhesion Molecule ◽  
Adhesion Assay ◽  
Intercellular Adhesion Molecule 1 ◽  
Endothelial Progenitor ◽  
Tnf Α ◽  
Factor Α

Objective To assess the effects of resveratrol (RSV) on expression of adhesion molecules in endothelial progenitor cells (EPCs) following tumor necrosis factor-α (TNF-α) stimulation. Methods EPCs were treated with RSV and stimulated with TNF-α. A mononuclear cell (MNC) adhesion assay was used to assess the effects of RSV on TNF-α-induced MNC adhesion. Vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin expression levels and nuclear factor κB (NF-κB) activation were assessed by immunoblotting. Results MNC adhesion to TNF-α-treated EPCs and VCAM-1/ICAM-1/E-selectin levels in EPCs were increased following TNF-α stimulation and decreased following RSV treatment. TNF-α enhanced NF-κB inhibitor α (IκB-α) phosphorylation in the cytosol as well as nuclear NF-κB p65 levels, both of which were decreased by RSV. Conclusions These findings provide new insights into RSV’s anti-inflammatory and anti-atherosclerotic effects. RSV’s mechanism of action might involve downregulation of VCAM-1, ICAM-1 and E-selectin by partial blockade of TNF-α-induced NF-κB activation and IκB-α phosphorylation in EPCs.

Neutralization of IL-18 attenuates lipopolysaccharide-induced myocardial dysfunction

2002 ◽  
Vol 283 (2) ◽  
pp. H650-H657 ◽  
Author(s):  
Christopher D. Raeburn ◽  
Charles A. Dinarello ◽  
Michael A. Zimmerman ◽  
Casey M. Calkins ◽  
Benjamin J. Pomerantz ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Cardiac Dysfunction ◽  
Myocardial Dysfunction ◽  
Left Ventricular ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Tnf Α ◽  
Developed Pressure ◽  
Factor Α ◽  
Cell Adhesion Molecule 1

Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) have been implicated in cardiac dysfunction during endotoxemia. Because IL-18 is a proinflammatory cytokine known to mediate the production of TNF-α and IL-1β and to induce the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), we hypothesized that neutralization of IL-18 would attenuate lipopolysaccharide (LPS)-induced cardiac dysfunction. Mice (C57BL/6) were injected with LPS (0.5 mg/kg ip) or vehicle (normal saline), and left ventricular developed pressure (LVDP) was determined by the Langendorff technique. LVDP was depressed by 38% at 6 h after LPS. LPS-induced myocardial dysfunction was associated with increased myocardial levels of TNF-α and IL-1β as well as increased expression of ICAM-1/VCAM-1. Pretreatment with neutralizing anti-mouse IL-18 antibody attenuated LPS-induced myocardial dysfunction (by 92%) and was associated with reduced myocardial IL-1β production (65% reduction) and ICAM-1/VCAM-1 expression (50% and 35% reduction, respectively). However, myocardial TNF-α levels were not influenced by neutralization of IL-18. In conclusion, neutralization of IL-18 protects against LPS-induced myocardial dysfunction. IL-18 may mediate endotoxemic myocardial dysfunction through induction of and/or synergy with IL-1β, ICAM-1, and VCAM-1.

Παθοφυσιολογία της αντίδρασης του ενδοθηλίου μετά από αγγειοπλαστική νεφρικής αρτηρίας

2014 ◽  
Author(s):  
Κυριακή Ταβερναράκη
Keyword(s):  
Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Vascular Cell Adhesion ◽  
Intercellular Adhesion Molecule 1 ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Tnf Α ◽  
Factor Α ◽  
Cell Adhesion Molecule 1 ◽  
Necrosis Factor

Σκοπός:Για τη μελέτη του παθοφυσιολογικού μηχανισμού αντίδρασης του τοιχώματος της νεφρικής αρτηρίας που εκλύεται κατά την αγγειοπλαστική με τοποθέτηση stent πραγματοποιήθηκε ποσοτικός προσδιορισμός έξι διαφορετικών παραγόντων φλεγμονής -μεσολαβητών (κυτοκίνες) στον ορό αίματος ασθενών που υποβλήθηκαν σε αυτήν την μέθοδο. Απώτερος σκοπός της μελέτης, μέσω της αξιολόγησης των διαφορών στις συγκεντρώσεις των μεσολαβητών σε ασθενείς που εμφάνισαν ή όχι επαναστένωση του αγγείου, είναι η αναγνώριση καποιού παράγοντα φλεγμονής που θα αποτελέσει δείκτη πρόβλεψης της επαναστένωσης με στόχο την πρόληψη αυτής.Υλικό - Μέθοδος:Μελετήθηκαν είκοσι δύο ασθενείς (17 άνδρες, μέσος όρος ηλικίας 66 έτη), με στένωση στην έκφυση της νεφρικής αρτηρίας και μή καλώς ρυθμιζόμενη υπέρταση, οι οποίοι υποβλήθησαν σε αγγειοπλαστική νεφρικής αρτηρίας με τοποθέτηση stent. Στους ασθενείς αυτούς πραγματοποιήθηκαν αιμοληψίες σε τρεις διαφορετικούς χρόνους: αμέσως πριν την αγγειοπλαστική (baseline), 24 ώρες και 6 μήνες μετά την αγγειοπλαστική και μετρήθηκαν στον ορό τους οι εξής μεσολαβητές: (1) Παράγοντας Νέκρωσης Όγκου-α (Tumor necrosis factor-α, TNF-α), (2) Ιντερλευκίνη 6 (Interleukin-6, IL-6), (3) Πρωτεΐνη χημειοτακτική για τα μονοκύτταρα τύπου-1 (Monocyte Chemoattractant protein-1, MCP-1), (4) Διακυτταρικό μόριο προσκόλλησης-1 (Intercellular adhesion molecule-1, ICAM-1), (5) Μόριο προσκόλλησης αγγειακών κυττάρων-1 (Vascular cell Adhesion Molecule-1, VCAM-1) και (6) Παράγοντας RANTES (Regulated upon Activation Normal T-cell Expressed presumed Secreted). Στους έξι μήνες μετά την αγγειοπλαστική πραγματοποιήθηκε έχρωμο Doppler υπερηχογράφημα και καταγράφηκε η ανάπτυξη ή όχι επαναστένωσης εντός του stent. Επιπλέον, αξιολογήθηκαν οι διαφορές της συγκέντρωσης αυτών σε ασθενείς που εμφάνισαν επαναστένωση της νεφρικής αρτηρίας στους 6 μήνες μετά την αγειοπλαστική συγκριτικά με αυτούς που δεν εμφάνισαν επαναστένωση.Αποτελέσματα:Η συγκέντρωση της ΙL-6 αυξήθηκε σημαντικά 24 ώρες μετά την αγγειοπλαστική (8.3 pg/mL ± 1.24 vs 2.76 pg/mL ± 1.27 τιμές baseline), ενώ στους 6 μήνες μετά επέστρεψε στις προ την επέμβαση τιμές (2.6 pg/mL ± 1.77) (Ρ<.0001). Δεν σημειώθηκαν στατιστικά σημαντικές διαφορές στις συγκεντρώσεις των υπολοίπων μεσολαβητών σε κανέναν από τους τρεις χρόνους. Επίσης, βρέθηκε πως η συγκέντρωση της ΙL-6 τόσο πρίν την αγγειοπλαστική όσο και 6 μήνες μετά την αγγειοπλαστική ήταν σημαντικά υψηλότερη στους ασθενείς που ανάπτυξαν επαναστένωση (8.13 pg/mL ± 4 vs 0.75 pg/mL ± 0.47 [P,.005] και 9.55 pg/ml ± 6.5 vs 0.42 pg/ml ± 0.35 [p<.02] αντίστοιχα).Συμπέρασμα:Με βάση τα αποτελέσματα προτείνουμε πως η αγγειοπλαστική της νεφρικής αρτηρίας με τοποθέτηση stent προκαλεί μια φλεγμονώδη αντίδραση στο τοίχωμα της αρτηρίας, όπως αυτή εκφράζεται με την υψηλή συγκέντρωση ΙL-6 στο αίμα 24 ώρες μετά την επέμβαση. Όσον αφορά στην ανάπτυξη ή όχι επαναστένωσης του αγγείου προτείνουμε πως η ΙL-6 μπορεί να να αναγνωρίσει τους ασθενείς υψηλού κινδύνου και κατ’ επέκταση να αποτελέσει έναν δείκτη πρόβλεψης της επαναστένωσης.

scholarly journals Non-invasively triggered spreading depolarizations induce a rapid pro-inflammatory response in cerebral cortex

2019 ◽  
Vol 40 (5) ◽  
pp. 1117-1131 ◽  
Author(s):  
Tsubasa Takizawa ◽  
Tao Qin ◽  
Andreia Lopes de Morais ◽  
Kazutaka Sugimoto ◽  
Joon Yong Chung ◽  
...  
Keyword(s):  
Gene Expression ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Tnf Α ◽  
Inflammatory Processes ◽  
Factor Α ◽  
The Relationship

Cortical spreading depolarization (CSD) induces pro-inflammatory gene expression in brain tissue. However, previous studies assessing the relationship between CSD and inflammation have used invasive methods that directly trigger inflammation. To eliminate the injury confounder, we induced CSDs non-invasively through intact skull using optogenetics in Thy1-channelrhodopsin-2 transgenic mice. We corroborated our findings by minimally invasive KCl-induced CSDs through thinned skull. Six CSDs induced over 1 h dramatically increased cortical interleukin-1β (IL-1β), chemokine (C-C motif) ligand 2 (CCL2), and tumor necrosis factor-α (TNF-α) mRNA expression peaking around 1, 2 and 4 h, respectively. Interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) were only modestly elevated. A single CSD also increased IL-1β, CCL2, and TNF-α, and revealed an ultra-early IL-1β response within 10 min. The response was blunted in IL-1 receptor-1 knockout mice, implicating IL-1β as an upstream mediator, and suppressed by dexamethasone, but not ibuprofen. CSD did not alter systemic inflammatory indices. In summary, this is the first report of pro-inflammatory gene expression after non-invasively induced CSDs. Altogether, our data provide novel insights into the role of CSD-induced neuroinflammation in migraine headache pathogenesis and have implications for the inflammatory processes in acute brain injury where numerous CSDs occur for days.

Cytokines induce NF-κB in activated but not in quiescent rat hepatic stellate cells

1998 ◽  
Vol 275 (2) ◽  
pp. G269-G278 ◽  
Author(s):  
C. Hellerbrand ◽  
C. Jobin ◽  
L. L. Licato ◽  
R. B. Sartor ◽  
D. A. Brenner
Keyword(s):  
Time Course ◽  
Nuclear Translocation ◽  
Stellate Cell ◽  
Nuclear Factor Κb ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Inflammatory Protein ◽  
Tnf Α ◽  
Cytokine Stimulation ◽  
Factor Α

The hepatic stellate cell (HSC), after a fibrogenic stimulus, is transformed from a quiescent to an activated phenotype, including the induction of responsiveness to a variety of agonists. We investigated the activation of nuclear factor-κB (NF-κB) and the expression of the NF-κB-responsive genes intercellular adhesion molecule 1 (ICAM-1) and macrophage inflammatory protein-2 (MIP-2) in freshly isolated and culture-activated HSC by tumor necrosis factor-α (TNF-α) or interleukin-1β. Inhibitor-κB was rapidly (<15 min) degraded, and NF-κB activity was induced in culture-activated but not in freshly isolated HSC after cytokine stimulation. After 30 min of stimulation, immunofluorescence revealed that the NF-κB p65 subunit was predominantly found in the nuclei of activated HSC compared with the cytoplasmic localization in unstimulated cells. No nuclear translocation appeared in freshly isolated HSC after stimulation, despite the presence of functional TNF-α receptors. NF-κB nuclear translocation appeared first partially after 4–5 days and completely after 9 days in culture. Consistent with this time course TNF-α induced the mRNA of the NF-κB-dependent genes ICAM-1 and MIP-2 in activated but not in quiescent HSC. Therefore, cytokines induce NF-κB activity and ICAM-1 and MIP-2 mRNAs in activated but not in quiescent HSC, through a postreceptor mechanism of regulation.

scholarly journals Ambient but not incremental oxidant generation effects intercellular adhesion molecule 1 induction by tumour necrosis factor α in endothelium

1998 ◽  
Vol 331 (3) ◽  
pp. 853-861 ◽  
Author(s):  
Toshiyuki ARAI ◽  
Susan A. KELLY ◽  
Matthew L. BRENGMAN ◽  
Manabu TAKANO ◽  
Elise H. SMITH ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Adhesion Molecule ◽  
Tumour Necrosis ◽  
Intercellular Adhesion Molecule ◽  
Tumour Necrosis Factor Α ◽  
Intercellular Adhesion Molecule 1 ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Proinflammatory cytokines upregulate endothelial adhesion molecule expression, thereby initiating the microvascular inflammatory response. We re-evaluated the reported role of reactive oxygen metabolites (ROMs) in signalling upregulation of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells by tumour necrosis factor α (TNF-α) in vitro. TNF-α upregulation of endothelial-cell ICAM-1 expression was inhibited by the cell-permeable antioxidants, or by the adenovirus-mediated intracellular overexpression of Cu,Zn-superoxide dismutase, but not by the exogenous (extracellular) administration of the cell-impermeable antioxidants, superoxide dismutase and/or catalase. This ICAM-1 upregulation was also inhibited by inhibitors of NADH dehydrogenase, cytochrome bc1 complex and NADPH oxidase. However, a measurable increase in net cellular ROM generation in response to TNF-α was not seen using four disparate sensitive ROM assays. Moreover, the stimulation of exogenous or endogenous ROM generation did not upregulate ICAM-1, nor enhance ICAM-1 upregulation by TNF-α. These findings suggest that an ambient background flux of ROMs, generated intracellularly, but not their net incremental generation, is necessary for TNF-α to induce ICAM-1 expression in endothelium in vitro.

Pneumocystis cariniiinduces ICAM-1 expression in lung epithelial cells through a TNF-α-mediated mechanism

1997 ◽  
Vol 273 (6) ◽  
pp. L1103-L1111 ◽  
Author(s):  
Mariette L. Yu ◽  
Andrew H. Limper
Keyword(s):  
Epithelial Cells ◽  
Pneumocystis Carinii ◽  
A549 Cells ◽  
Lung Epithelial Cells ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Respiratory Impairment ◽  
Type Ii Pneumocytes ◽  
Tnf Α ◽  
Factor Α

Inflammatory cell recruitment contributes to respiratory impairment during Pneumocystis carinii pneumonia. We evaluated expression of intercellular adhesion molecule-1 (ICAM-1), a key participant in leukocyte accumulation, in rats with P. carinii pneumonia. Immunostaining for ICAM-1 was most marked on bronchiolar epithelium but was also evident on type II pneumocytes, endothelium, and macrophages. Lung from normal and dexamethasone-treated uninfected animals exhibited markedly less ICAM-1. We hypothesized that P. carinii promoted ICAM-1 expression in epithelium through tumor necrosis factor-α (TNF-α) release from macrophages or that P. carinii directly stimulated ICAM-1 expression. Alveolar macrophages were incubated with P. carinii, and the medium was added to A549 epithelial cells. Treatment of macrophages with P. carinii enhanced A549 ICAM-1, which was inhibited with antibody to TNF-α. To determine whether P. carinii alone also stimulated ICAM-1, A549 cells were cultured with P. carinii, also augmenting ICAM-1. Of note, A549 ICAM-1 expression from P. carinii alone was less than with P. carinii-exposed macrophages. Thus ICAM-1 is enhanced in lung epithelium during P. carinii infection, in part, through TNF-α-mediated mechanisms.

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