scholarly journals Manipulation of Quercetin and Melatonin in the Down-Regulation of HIF-1α, HSP-70 and VEGF Pathways in Rat’s Kidneys Induced by Hypoxic Stress

Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582094979
Author(s):  
Aliah R. Alshanwani ◽  
Sameerah Shaheen ◽  
Laila M. Faddah ◽  
Ahlam M. Alhusaini ◽  
Hanaa M. Ali ◽  
...  

Hypoxia may lead to inflammatory responses by numerous signaling pathways. This investigation intended to inspect the defensive role of Quercetin (Quer) and/ or Melatonin (Mel) against reno toxicity induced by Sodium nitrite (Sod ntr). Sod ntr injection significantly decreased blood hemoglobin concentration (Hb) with a concurrent increase in serum tumor necrosis factor- α, interleukin-6, C-reactive protein, creatinine, and urea levels. Over protein-expression of vascular endothelial growth factor and heat shock, protein-70 and mRNA of HIF-1α were also observed. Pretreatment of the Sod ntr- injected rats with the aforementioned antioxidants; either alone or together significantly improved such parameters. Histopathological examination reinforced the previous results. It was concluded that the combined administration of Quer and Mel may be useful as a potential therapy against renal injury induced by Sod ntr. HIF-1α and HSP-70 are implicated in the induction of hypoxia and its treatment.

Dose-Response ◽  
2018 ◽  
Vol 16 (4) ◽  
pp. 155932581881218 ◽  
Author(s):  
Laila M. Fadda ◽  
Hanan Hagar ◽  
Azza M. Mohamed ◽  
Hanaa M. Ali

Titanium dioxide nanoparticles (TiO2-NPs) are extensively used in a wide range of applications; however, many reports have investigated their nanotoxicological effect at the molecular level either in vitro or in vivo systems. The defensive roles of quercetin (Qur) or idebenone (Id) against the hepatotoxicity induced by TiO2-NPs were evaluated in the current study. The results showed that the coadministration of Qur or Id to rats intoxicated with TiO2-NPs markedly ameliorated the elevation in hepatic malondialdehyde (MDA), serum alanine amino-transferase (ALT), glucose, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), immunoglobin G (IgG), and C-reactive protein (CRP) levels compared to their levels in TiO2-NPs-treated rats. The aforementioned antioxidants also effectively modulated the changes in the levels of serum vascular endothelial growth factor (VEGF), nitric oxide (NO), hepatic DNA breakage, caspase-3, and inhibition of drug metabolizing enzymes (cytochrome P450s; CYP4502E12E1) in rat livers induced by TiO2-NPs toxicity. The histopathological examination of the liver section showed that TiO2-NPs caused severe degeneration of most hepatocytes with an increase in collagen in the portal region, while treatment with the antioxidants in question improved liver architecture. These outcomes supported the use of Qur and Id as protective agents against the hepatotoxicity induced by TiO2-NPs and other hepatotoxic drugs.


Author(s):  
Eun S. Park ◽  
Sehee Kim ◽  
Derek. C. Yao ◽  
Jude P.J. Savarraj ◽  
H. Alex Choi ◽  
...  

Increased soluble endoglin (sENG) were observed in human brain arteriovenous malformations (bAVMs), and overexpression of sENG with vascular endothelial growth factor (VEGF)-A induced dysplastic vessel formation in mouse brain. However, the underlying mechanism of sENG-induced vascular malformations is not clear. While evidence suggests the role of sENG as a pro-inflammatory modulator, increased microglial accumulation and inflammations were observed in bAVMs. Therefore, we hypothesized that microglia mediate sENG-induced inflammation and endothelial cell (EC) dysfunction in bAVMs. In this study, we confirmed that sENG with VEGF-A overexpression induced dysplastic vessel formation. Remarkably, there were increased microglial activation around dysplastic vessels with expression of NLRP3, inflammasome marker. We found that sENG increased the gene expression of VEGF-A, pro-inflammatory cytokines/inflammasome mediators (TNF-α, IL-6, NLRP3, ASC, Caspase-1, and IL-1β), and proteolytic enzyme (MMP-9) in BV2 microglia. The conditioned media from sENG-treated BV2 (BV2-sENG-CM) significantly increased angiogenic factors (Notch-1 and TGFβ) and pERK1/2 in ECs while it decreased IL-17RD, an anti-angiogenic mediator. Finally, the BV2-sENG-CM significantly increased EC migration and tube formation. Together, our study demonstrates that sENG provokes microglia to release angiogenic/inflammatory responses which may be involved in EC dysfunction. Our study suggests the contribution of microglia in the pathology of sENG-associated vascular malformations.


2009 ◽  
Vol 101 (03) ◽  
pp. 521-526 ◽  
Author(s):  
Francesco Sofi ◽  
Roberto Caporale ◽  
Andrea Capalbo ◽  
Rossella Marcucci ◽  
Claudio Macchi ◽  
...  

SummaryNo data are available about the possible role of endothelial progenitor cells (EPCs), cytochemokines and N-terminal pro-brain natriuretic peptide (NT-proBNP) in determining a different response to short period of cardiologic rehabilitation (CR), as measured by the improvement of exercise capacity. In a population of 86 cardiac surgery patients, we evaluated the numbers of EPCs, pro- and anti-inflammatory cytokines (IL-6,IL-8, IL-10, IL-1ra), hs-C-reactive protein (CRP), vascular endothelial growth factor (VEGF) and NT-proBNP before (T1), and after 15 days of CR (T2). EPCs were measured by flow cytometry, and the exercise capacity was measured at T1 and T2 by using the six-minute walk test (6MWT). At T2, a significant increase of 6MWT (p<0.0001) was detected. No significant increase of EPCs was observed, while a significant (at least p<0.05) decrease in cytochemokines, CRP and NT-ProBNP levels was evidenced. By analyzing the median improvement of 6MWT, only patients with a median improvement ≥23% showed a significant (p<0.05) increase of EPCs at T2, with significant correlations between EPCs, VEGF and IL-10. On the contrary, in patients with a median improvement <23% a negative correlation between CRP and EPCs was observed. Finally, CD34+/KDR+ EPCs showed significant correlation with IL-8 at T1. In conclusion, a short period of CR intervention determines a different pattern of modifications for EPCs in relation to the improvement of exercise capacity.


2017 ◽  
Vol 95 (7) ◽  
pp. 618-622
Author(s):  
Serafima Ya. Tazina ◽  
T. A. Fedorova ◽  
N. A. Semenenko ◽  
A. P. Roitman ◽  
V. I. Burtsev ◽  
...  

The peculiarities of primary and secondary infective endocarditis (IE) were studied in 62 patients with primary and secondary IE, uncomplicated and complicated disease treated in S. P. Botkin city clinical hospital including analysis of dynamics of tumor necrosis factor α (TNF α), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF) within 3 weeks after the onset of antibiotic therapy. A rise in TNF α and IL-6 levels was shown to correlate with the severity of the disease and the development of infectious-toxic syndrome. Most patients had an increased level of VEGF, a mediator involved in the regulation of inflammation. It was shown that combination of high TNF-α and IL-6 levels with the initially low or gradually increasing VEGF levelsuggests the unfavourable prognosis characteristic of the most heavily diseased anddeceased patients.


JHEP Reports ◽  
2021 ◽  
Vol 3 (3) ◽  
pp. 100251
Author(s):  
Valeria Mariotti ◽  
Romina Fiorotto ◽  
Massimiliano Cadamuro ◽  
Luca Fabris ◽  
Mario Strazzabosco

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 253
Author(s):  
Xi Guo ◽  
Hong Yi ◽  
Tin Chiu Li ◽  
Yu Wang ◽  
Huilin Wang ◽  
...  

Vascular endothelial growth factor (VEGF) is a well-known angiogenic factor that plays a critical role in various physiological and pathological processes. VEGF also contributes to the process of embryo implantation by enhancing embryo development, improving endometrial receptivity, and facilitating the interactions between the developing embryo and the endometrium. There is a correlation between the alteration of VEGF expression and reproductive failure, including recurrent implantation failure (RIF) and recurrent miscarriage (RM). In order to clarify the role of VEGF in embryo implantation, we reviewed recent literature concerning the expression and function of VEGF in the reproductive system around the time of embryo implantation and we provide a summary of the findings reported so far. We also explored the effects and the possible underlying mechanisms of action of VEGF in embryo implantation.


2020 ◽  
Vol 39 (11) ◽  
pp. 1528-1544 ◽  
Author(s):  
HE Abo Mansour ◽  
MM El-Batsh ◽  
NS Badawy ◽  
ET Mehanna ◽  
NM Mesbah ◽  
...  

This study aimed to investigate the potential role of co-treatment with doxorubicin (DOX) and verapamil (VRP) nanoparticles in experimentally induced hepatocellular carcinoma in mice and to investigate the possible mechanisms behind the potential favorable effect of the co-treatment. DOX and VRP were loaded into chitosan nanoparticles (CHNPs), and cytotoxicity of loaded and unloaded drugs against HepG2 cells was evaluated. Male albino mice were divided into eight groups ( n = 15): (1) normal control, (2) diethylnitrosamine, (3) CHNPs, (4) free DOX, (5) CHNPs DOX, (6) free VRP, (7) CHNPs VRP, and (8) CHNPs DOX + CHNPs VRP. Either VRP or DOX loaded into CHNPs showed stronger growth inhibition of HepG2 cells than their free forms. DOX or VRP nanoparticles displayed pronounced anticancer activity in vivo through the decline of vascular endothelial growth factor and B cell lymphoma-2 contents in liver tissues, upregulation of antioxidant enzymes, and downregulation of multidrug resistance 1. Moreover, reduced cardiotoxicity was evident from decreased level of tumor necrosis factor-α and malondialdehyde in heart tissues coupled with decreased serum activity of creatine kinase-myocardial band and lactate dehydrogenase. Co-treatment with CHNPs DOX and CHNPs VRP showed superior results versus other treatments. Liver sections from the co-treatment group revealed the absence of necrosis, enhanced apoptosis, and nearly normal hepatic lobule architecture. Co-treatment with CHNPs DOX and CHNPs VRP revealed enhanced anticancer activity and decreased cardiotoxicity versus the corresponding free forms.


2017 ◽  
Vol 68 (4) ◽  
pp. 326-329
Author(s):  
Piotr Barć ◽  
Tomasz Płonek ◽  
Dagmara Baczyńska ◽  
Artur Pupka ◽  
Wojciech Witkiewicz ◽  
...  

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