Alpha-Terpineol as Antitumor Candidate in Pre-Clinical Studies

2021 ◽  
Vol 21 ◽  
Author(s):  
Helber A. Negreiros ◽  
Kariely G. de Moura ◽  
Maria L.L.B. do Nascimento ◽  
Débora C.N. Rodrigues ◽  
Paulo M.P. Ferreira ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Viability ◽  
Dna Fragmentation ◽  
Membrane Integrity ◽  
Micronucleus Assay ◽  
Sarcoma 180 ◽  
Cell Membrane Integrity ◽  
Anti Tumor Activity ◽  
Murine Sarcoma ◽  
Early Late

Background: Alpha-terpineol is a monoterpene alcohol with anti-tumor activity against different tumor cell lines (lung, breast, leukemias and colorectal) through blockage of NF-kB expression, which play an important role in tumor cells growth. Objective: Evaluate the antitumor activity of alpha-terpineol in murine Sarcoma 180 cell line Methods: For the tests, different cytotoxic and genotoxic assays were used, including Trypan blue, cytokinesis-blocked micronucleus assay, comet assay, agarose gel DNA fragmentation, flow cytometry and cell viability using fluorescence. Ascitic fluid cells from sarcoma 180 were obtained from Mus musculus peritoneal cavity and Alpha-terpineol was tested at 100, 250 and 500 μg/mL. Doxorubicin and Cisplatin were used as positive controls. Results: Cytotoxic effects of alpha-terpineol were found in all concentrations tested, reducing cell viability in 50.9; 38.53; 30.82% at 100, 250 and 500 μg/mL, respectively. Alpha-terpineol induced genotoxic effects due to DNA fragmentation (increased frequency and index of damage), and was clastogenic by increased micronuclei formation, nucleoplasmic bridges and nuclear buds. DNA fragmentation and increased cell death indicated that alpha-terpineol can cause early, late, and necrotic apoptosis. Conclusion: Our data indicate that alpha-terpineol has antitumor activity revealed by cytogenetic mechanisms and / or loss of cell membrane integrity.

Celastrol ameliorates acetaminophen-induced oxidative stress and cytotoxicity in HepG2 cells

2017 ◽  
Vol 37 (7) ◽  
pp. 742-751 ◽  
Author(s):  
AT Jannuzzi ◽  
M Kara ◽  
B Alpertunga
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Hepg2 Cells ◽  
Membrane Integrity ◽  
Neutral Red ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Tripterygium Wilfordii Hook F ◽  
Cell Membrane Integrity ◽  
And Oxidative Stress

Acetaminophen (APAP) is the most commonly used analgesic and antipyretic drug in the world. However, hepatotoxicity caused by APAP overdose is the most frequent cause of acute liver failure worldwide and oxidative stress involved in the pathogenesis of APAP hepatotoxicity. Celastrol is a natural triterpenoid derived from Tripterygium wilfordii Hook F. that exhibits antioxidant, anti-inflammatory, and antitumor activities. In this study, we aimed to investigate the potential ameliorative effects of celastrol against APAP-induced cytotoxicity and oxidative stress. Human hepatocellular carcinoma cells (HepG2) were incubated with 20 mM of APAP for 24 h and posttreated with 50 nM, 100 nM, or 200 nM of celastrol for a further 24 h. The methylthiazolyldiphenyl-tetrazolium bromide, lactate dehydrogenase, and neutral red uptake assays showed celastrol posttreatments recovered cell viability and cell membrane integrity in a concentration-dependent manner. Celastrol posttreatments exerted a significant increase in the glutathione content and a decrease in the malondialdehyde and protein carbonylation levels. Also, celastrol posttreatments attenuated the APAP-induced oxidative stress by raising glutathione peroxidase, glutathione reductase, and catalase activities. However, superoxide dismutase activity did not change. In conclusion, celastrol treatment may improve cell viability and increase cellular antioxidant defense in HepG2 cells. These results suggest that celastrol may have the potential to ameliorate the APAP-induced oxidative stress and cytotoxicity.

scholarly journals Tailoring material properties of cellulose sponges through surface plasma modification for clinical applications

2020 ◽  
pp. 1-13
Author(s):  
Anne Krüger-Genge ◽  
Olivia Mauger ◽  
Sophia Westphal ◽  
Stefanie Klöpzig ◽  
Werner Müller ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Cell Viability ◽  
Cell Lines ◽  
Metabolic Activity ◽  
Material Properties ◽  
Cho Cells ◽  
Membrane Integrity ◽  
Plasma Modification ◽  
Simple Modification ◽  
Cell Membrane Integrity

BACKGROUND: Within the last years the investigation of cellulosic materials got into the focus of biomaterial research due to biocompatibility, sustainability, ubiquitous deposits and the potential of simple modification. Thereby this material is an ideal candidate to tailor material properties as charge, swelling, hydrophilicity and elasticity to clinical demands. OBJECTIVE: In this study a cellulose-based material was functionalized using plasma and gas (O2, N2, silane). METHODS: The effect of material modification on two cell lines using different animal species was investigated using indirect and direct cytotoxicity analysis. The following parameters were investigated: number of adherent cells, cell viability, metabolic activity, cell membrane integrity and morphology. RESULTS: Pristine and functionalized material eluates did not harm L929 cells and could be classified as non-cytotoxic according to DIN-EN-ISO 10993. A direct seeding of CHO-cells onto material surfaces showed a similar result. None of the conducted modifications had a negative effect on CHO-cells. Interestingly, parameters investigated during the study were positively influenced after material functionalization. In special, the treatment of cellulose with silane improved cell viability, metabolic activity, cellular adherence and cell membrane integrity significantly. CONCLUSIONS: Within this study the potential of cellulose-based material functionalization with tailorable effects on different cell lines was proven. This indicates that all investigated medical grade sponge materials are promising polymers for applications in clinical routine.

scholarly journals Dance Training Improves Cytokine Secretion and Viability of Neutrophils in Diabetic Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Leandro Borges ◽  
Maria E. P. Passos ◽  
Maysa B. B. Silva ◽  
Vinicius C. Santos ◽  
César M. Momesso ◽  
...  
Keyword(s):  
Dna Fragmentation ◽  
Plasma Levels ◽  
Interleukin 1 ◽  
Membrane Integrity ◽  
Neutrophil Function ◽  
Moderate Intensity ◽  
Control Group ◽  
Diabetic Patients ◽  
Cell Membrane Integrity ◽  
Dance Training

Background. Evidence suggests that exercise improves neutrophil function. The decreased functional longevity of neutrophils and their increased clearance from infectious sites contribute to the increased susceptibility to infection and severity of infection observed in patients with diabetes. Objective. Herein, we investigated the effects of a dance program on neutrophil number, function, and death in type 2 diabetes mellitus (T2DM) patients and healthy volunteers. Methods. Ten patients with T2DM and twelve healthy individuals participated in a moderate-intensity dance training program for 4 months. The plasma levels of leptin, free fatty acids (FFAs), tumour necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin-1β (IL-1β), and interleukin-1 receptor antagonist (IL-1ra); neutrophil counts; extent of DNA fragmentation; cell membrane integrity; and production of TNF-α, interleukin-8 (IL-8), interleukin-6 (IL-6), and IL-1β in neutrophils were measured before and after training. Results. Training reduced plasma levels of TNF-α (1.9-fold in controls and 2.2-fold in patients with T2DM) and CRP (1.4-fold in controls and 3.4-fold in patients with T2DM). IL-1ra levels were higher in the control group (2.2-fold) after training. After training, neutrophil DNA fragmentation was decreased in patients with T2DM (90%), while the number of neutrophils increased (70% in controls and 1.1-fold in patients with T2DM). Conclusion. Dance training is a nonpharmacological strategy to reduce inflammation and improve neutrophil clearance in patients with T2DM.

scholarly journals Non-invasive assessment of porcine oocyte quality by supravital staining of cumulus–oocyte complexes with lissamine green B

Zygote ◽  
2015 ◽  
Vol 24 (3) ◽  
pp. 418-427 ◽  
Author(s):  
Rahul Dutta ◽  
Shun Li ◽  
Konrad Fischer ◽  
Alexander Kind ◽  
Tatiana Flisikowska ◽  
...  
Keyword(s):  
Dna Fragmentation ◽  
Cumulus Cell ◽  
Membrane Integrity ◽  
Developmental Competence ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Low Grade ◽  
Cell Membrane Integrity ◽  
Non Invasive ◽  
Lissamine Green

SummaryWe evaluated the usefulness of lissamine green B (LB) staining of cumulus–oocyte complexes (COC) as a non-invasive method of predicting maturational and developmental competence of slaughterhouse-derived porcine oocytes cultured in vitro. Cumulus cells of freshly aspirated COCs were evaluated either morphologically on the basis of thickness of cumulus cell layers, or stained with LB, which penetrates only non-viable cells. The extent of cumulus cell staining was taken as an inverse indicator of membrane integrity. The two methods of COC grading were then examined as predictors of nuclear maturation and development after parthenogenetic activation. In both cases LB staining proved a more reliable indicator than morphological assessment (P < 0.05). The relationship between LB staining and cumulus cell apoptosis was also examined. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay for DNA fragmentation revealed that oocytes within COCs graded as low quality by either LB staining or visual morphology showed significantly greater DNA fragmentation (P < 0.05) than higher grades, and that LB and visual grading were of similar predictive value. Expression of the stress response gene TP53 showed significantly higher expression in COCs graded as low quality by LB staining. However expression of the apoptosis-associated genes BAK and CASP3 was not significantly different between high or low grade COCs, suggesting that mRNA expression of BAK and CASP3 is not a reliable method of detecting apoptosis in porcine COCs. Evaluation of cumulus cell membrane integrity by lissamine green B staining thus provides a useful new tool to gain information about the maturational and developmental competence of porcine oocytes.

Quercetin in attenuation of ischemic/reperfusion injury: A review

2020 ◽  
Vol 13 ◽  
Author(s):  
Milad Ashrafizadeh ◽  
Saeed Samarghandian ◽  
Kiavash Hushmandi ◽  
Amirhossein Zabolian ◽  
Md Shahinozzaman ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Membrane ◽  
Blood Supply ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Membrane Integrity ◽  
Therapeutic Effects ◽  
Molecular Pathways ◽  
Cell Membrane Integrity ◽  
Cell Membrane Disruption

Background: Ischemia/reperfusion (I/R) injury is a serious pathologic event that occurs due to restriction in blood supply to an organ, followed by hypoxia. This condition leads to enhanced levels of pro-inflammatory cytokines such as IL-6 and TNF-, and stimulation of oxidative stress via enhancing reactive oxygen species (ROS) levels. Upon reperfusion, blood supply increases, but it deteriorates condition, and leads to generation of ROS, cell membrane disruption and finally, cell death. Plant derived-natural compounds are well-known due to their excellent antioxidant and anti-inflammatory activities. Quercetin is a flavonoid exclusively found in different vegetables, herbs, and fruits. This naturally occurring compound possesses different pharmacological activities making it appropriate option in disease therapy. Quercetin can also demonstrate therapeutic effects via affecting molecular pathways such as NF-B, PI3K/Akt and so on. Methods: In the present review, we demonstrate that quercetin administration is beneficial in ameliorating I/R injury via reducing ROS levels, inhibition of inflammation, and affecting molecular pathways such as TLR4/NF-B, MAPK and so on. Results and conclusion: Quercetin can improve cell membrane integrity via decreasing lipid peroxidation. Apoptotic cell death is inhibited by quercetin via down-regulation of Bax, and caspases, and upregulation of Bcl-2. Quercetin is able to modulate autophagy (inhibition/induction) in decreasing I/R injury. Nanoparticles have been applied for delivery of quercetin, enhancing its bioavailability and efficacy in alleviation of I/R injury. Noteworthy, clinical trials have also confirmed the capability of quercetin in reducing I/R injury.

scholarly journals Biological Effects of XyloCore, a Glucose Sparing PD Solution, on Mesothelial Cells: Focus on Mesothelial-Mesenchymal Transition, Inflammation and Angiogenesis

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2282
Author(s):  
Valentina Masola ◽  
Mario Bonomini ◽  
Maurizio Onisto ◽  
Pietro Manuel Ferraro ◽  
Arduino Arduini ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Viability ◽  
Biological Effects ◽  
Membrane Integrity ◽  
Glucose Content ◽  
Mesenchymal Transition ◽  
Low Glucose ◽  
Endothelial To Mesenchymal Transition ◽  
Osmotic Agents

Glucose-based solutions remain the most used osmotic agents in peritoneal dialysis (PD), but unavoidably they contribute to the loss of peritoneal filtration capacity. Here, we evaluated at a molecular level the effects of XyloCore, a new PD solution with a low glucose content, in mesothelial and endothelial cells. Cell viability, integrity of mesothelial and endothelial cell membrane, activation of mesothelial and endothelial to mesenchymal transition programs, inflammation, and angiogenesis were evaluated by several techniques. Results showed that XyloCore preserves mesothelial and endothelial cell viability and membrane integrity. Moreover XyloCore, unlike glucose-based solutions, does not exert pro-fibrotic, -inflammatory, and -angiogenic effects. Overall, the in vitro evidence suggests that XyloCore could represent a potential biocompatible solution promising better outcomes in clinical practice.

scholarly journals Integrating flexible electronics for pulsed electric field delivery in a vascularized 3D glioblastoma model

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Marie C. Lefevre ◽  
Gerwin Dijk ◽  
Attila Kaszas ◽  
Martin Baca ◽  
David Moreau ◽  
...  
Keyword(s):  
Electric Field ◽  
Electric Fields ◽  
Flexible Electronics ◽  
Soft Tissues ◽  
Multiphoton Microscopy ◽  
Membrane Integrity ◽  
Tumor Model ◽  
Pulsed Electric Fields ◽  
In Ovo ◽  
Cell Membrane Integrity

AbstractGlioblastoma is a highly aggressive brain tumor, very invasive and thus difficult to eradicate with standard oncology therapies. Bioelectric treatments based on pulsed electric fields have proven to be a successful method to treat cancerous tissues. However, they rely on stiff electrodes, which cause acute and chronic injuries, especially in soft tissues like the brain. Here we demonstrate the feasibility of delivering pulsed electric fields with flexible electronics using an in ovo vascularized tumor model. We show with fluorescence widefield and multiphoton microscopy that pulsed electric fields induce vasoconstriction of blood vessels and evoke calcium signals in vascularized glioblastoma spheroids stably expressing a genetically encoded fluorescence reporter. Simulations of the electric field delivery are compared with the measured influence of electric field effects on cell membrane integrity in exposed tumor cells. Our results confirm the feasibility of flexible electronics as a means of delivering intense pulsed electric fields to tumors in an intravital 3D vascularized model of human glioblastoma.

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