Antioxidative, anticancer and genotoxic properties of α-pinene on N2a neuroblastoma cells

Biologia ◽  
2013 ◽  
Vol 68 (5) ◽  
Author(s):  
Elanur Aydin ◽  
Hasan Türkez ◽  
Fatime Geyikoğlu
Keyword(s):  
Biological Activities ◽  
Neuroblastoma Cells ◽  
Cell Types ◽  
Mean Values ◽  
N2a Cells ◽  
Diphenyltetrazolium Bromide ◽  
Total Antioxidant ◽  
Total Oxidative Stress ◽  
Oxidative Effects

Abstractα-Pinene, an organic monoterpene, is found in essential oils of pine and coniferous trees. To date, although various biological activities of α-pinene have been demonstrated, its neurotoxicity has never been explored. Therefore in this study, we aimed to describe in vitro antiproliferative and/or cytotoxic properties by 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, genotoxic damage potentials by single cell gel electrophoresis, and oxidative effects by total antioxidant capacity (TAC) and total oxidative stress (TOS) analysis of α-pinene. Statistical analysis of MTT assay results indicated significant (p < 0.05) decreases of the cell proliferation rates in healthy neurons treated with α-pinene at only 400 mg/L, while significant decreases were observed in N2a cells at 100, 200 and 400 mg/L. On the other hand, the mean values of the total scores of cells showing DNA damage were not found significantly different from the control values on both cells. In addition, our results indicated that 10 and 25 mg/L of α-pinene treatment caused increases of TAC levels in primary rat neurons without any alterations of its level in N2a cells. However, α-pinene treatments at higher doses led to increases of TOS levels in both cell types. Overall our results suggest that α-pinene is of a limited therapeutic use as an anticancer agent.

scholarly journals Anticancer and Antioxidant Properties of Terpinolene in Rat Brain Cells

2013 ◽  
Vol 64 (3) ◽  
pp. 415-424 ◽  
Author(s):  
Elanur Aydin ◽  
Hasan Türkez ◽  
Şener Taşdemir
Keyword(s):  
Biological Activities ◽  
Antioxidant Properties ◽  
Neuroblastoma Cells ◽  
In Vitro Study ◽  
Cell Types ◽  
Damage Potential ◽  
Total Antioxidant ◽  
Antiproliferative Agent ◽  
Total Oxidative Stress

Abstract Terpinolene (TPO) is a natural monoterpene present in essential oils of many aromatic plant species. Although various biological activities of TPO have been demonstrated, its neurotoxicity has never been explored. In this in vitro study we investigated TPO’s antiproliferative and/or cytotoxic properties using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) test, genotoxic damage potential using the single-cell gel electrophoresis (SCGE), and oxidative effects through total antioxidant capacity (TAC) and total oxidative stress (TOS) in cultured primary rat neurons and N2a neuroblastoma cells. Dose-dependent effects of TPO (at 10 mg L-1, 25 mg L-1, 50 mg L-1, 100 mg L-1, 200 mg L-1, and 400 mg L-1) were tested in both cell types. Significant (P<0.05) decrease in cell proliferation were observed in cultured primary rat neurons starting with the dose of 100 mg L-1 and in N2a neuroblastoma cells starting with 50 mg L-1. TPO was not genotoxic in either cell type. In addition, TPO treatment at 10 mg L-1, 25 mg L-1, and 50 mg L-1 increased TAC in primary rat neurons, but not in N2a cells. However, at concentrations above 50 mg L-1 it increased TOS in both cell types. Our findings clearly demonstrate that TPO is a potent antiproliferative agent for brain tumour cells and may have potential as an anticancer agent, which needs to be further studied.

Zingiberene attenuates hydrogen peroxide-induced toxicity in neuronal cells

2014 ◽  
Vol 34 (2) ◽  
pp. 135-144 ◽  
Author(s):  
B Togar ◽  
H Türkez ◽  
AD Stefano ◽  
A Tatar ◽  
D Cetin
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Mean Values ◽  
Oxidative Damages ◽  
Cortex Cell ◽  
Diphenyltetrazolium Bromide ◽  
Total Antioxidant ◽  
Total Oxidative Stress ◽  
First Time

In this experimental design, we explored the neuroprotective potential of zingiberene (ZGB), a monocyclic sesquiterpene, in hydrogen peroxide (H2O2)-induced toxicity in newborn rat cerebral cortex cell cultures for the first time. The rats were exposed to H2O2 for 6 h to determine the oxidative stress levels. To evaluate cell viability, both 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays were carried out. Total antioxidant capacity (TAC) and total oxidative stress (TOS) parameters were used to evaluate oxidative changes. Besides determining 8-hydroxy-2-deoxyguanosine (8-OH-dG) levels in vitro, single-cell gel electrophoresis was also performed to measure the resistance of neuronal DNA to H2O2- exposed rats. Our results showed that survival and TAC levels of the cells decreased, while TOS, 8-OH-dG levels and the mean values of the total scores of cells showing DNA damage increased in the H2O2 alone-treated cultures. But pretreatment of ZGB suppressed the cytotoxicity, genotoxicity and oxidative stress that were increased by H2O2. Based on these observations, it is suggested that the sesquiterpene ZGB can be used as a novel and natural potential therapeutic in counteracting oxidative damages in the field of neurodegenerative disorders.

scholarly journals Antiproliferative, genotoxic and oxidant activities of cyclosativene in rat neuron and neuroblastoma cell lines

2014 ◽  
Vol 66 (3) ◽  
pp. 1171-1177
Author(s):  
Başak Toğar ◽  
Hasan Türkez ◽  
Fatime Geyikoğlu ◽  
Ahmet Hacimüftüoğlu ◽  
Abdulgani Tatar
Keyword(s):  
Dna Damage ◽  
Cell Lines ◽  
Neuroblastoma Cell ◽  
Cell Types ◽  
Damage Potential ◽  
Mean Values ◽  
Abies Magnifica ◽  
Total Antioxidant ◽  
Total Oxidative Stress

Cyclosativene (CSV) is a tetracyclic sesquiterpene found in the essential oils of Centaurea cineraria (Asteraceae) and Abies magnifica A. Murray (Pinaceae) plants. To the best of our knowledge, its cytotoxic, genotoxic and oxidant effects have never been studied on any cell lines. Therefore, we aimed to investigate the in vitro antiproliferative and/or cytotoxic properties, antioxidant/oxidant activity and genotoxic damage potential of CSV in healthy neurons and N2a neuroblastoma (N2a-NB) cell cultures. After treatment with 10-400 ?g/ml of CSV for 24 h, cell proliferation was measured by the MTT (3,(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The antioxidant activity was assessed by the total antioxidant capacity (TAC) and total oxidative stress (TOS) assays. To evaluate the level of DNA damage, single cell gel alkaline electrophoresis (SCGE) was used. The MTT assay showed that the application of CSV significantly reduced cell viability in both cell types. CSV treatments at higher doses led to decreases of TAC levels and increases of TOS levels in neuron and N2a-NB cells. The mean values of the total scores of cells showing DNA damage were not found to be significantly different from the control values in both cells. In conclusion, this study suggests that CSV has weak anticancer potential.

scholarly journals The in vitro cytotoxicity, genotoxicity and oxidative damage potential of dapagliflozin, on cultured human blood cells

2019 ◽  
Vol 44 (5) ◽  
pp. 692-698
Author(s):  
Kenan Çadırcı ◽  
Özlem Özdemir Tozlu ◽  
Hasan Türkez
Keyword(s):  
Human Blood ◽  
Blood Cells ◽  
In Vitro Cytotoxicity ◽  
Damage Potential ◽  
Human Blood Cells ◽  
Diphenyltetrazolium Bromide ◽  
Total Antioxidant ◽  
Release Assay ◽  
Total Oxidative Stress

Abstract Objectives Dapagliflozin (DAPA), is a potent SGLT-2 inhibitor for the treatment of patients with type 2 diabetes. DAPA has a good clinical and biological tolerance profile. However little information is available on its potential effects on cultured human blood cells. The evaluation of the in vitro cytotoxicity, genotoxicity potential and antioxidant/oxidant activity of DAPA in primary human whole blood cell cultures was aimed in this study. Materials and methods Cell viability was measured by the MTT [3,(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and lactate dehydrogenase (LDH) leakage assays. The antioxidant/oxidant activity was determined by measuring the total antioxidant capacity (TAC) and total oxidative stress (TOS) levels. To assess the genotoxicity of DAPA, chromosomal aberration (CA) frequencies were determined. Results MTT and LDH release assay exhibited that exposure to different doses of DAPA did not changed significantly the proliferation of cells. The results of TAC and TOS assays were showed that TAC level was elevated while TOS level did not altered in DAPA-treated cells. Moreover, any increase in the frequency of CA did not found on cultures blood cells. Conclusion These data indicate that DAPA has not cytotoxic and genotoxic potential in cultured human blood cells, also, induces the increasing antioxidant activity.

Effects of two lichen acids isolated from Pseudevernia furfuracea (L.) Zopf in cultured human lymphocytes

2018 ◽  
Vol 73 (7-8) ◽  
pp. 303-312 ◽  
Author(s):  
Bugrahan Emsen ◽  
Basak Togar ◽  
Hasan Turkez ◽  
Ali Aslan
Keyword(s):  
Oxidative Stress ◽  
Lactate Dehydrogenase ◽  
Cytotoxic Effect ◽  
Human Lymphocytes ◽  
Pseudevernia Furfuracea ◽  
Low Concentrations ◽  
Diphenyltetrazolium Bromide ◽  
Total Antioxidant ◽  
Total Oxidative Stress

Abstract The present study aims at assessing the efficacies of olivetoric acid (OA) and physodic acid (PA) isolated from Pseudevernia furfuracea (L.) Zopf (Parmeliaceae) in human lymphocytes (HLs) in vitro. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays were performed to establish cytotoxicity in HLs. Besides, oxidative stress and genotoxicity were monitored by estimating the changes of total oxidative stress (TOS) and 8-hydroxy-2′-deoxyguanosine (8-OH-dG) levels, respectively, in HLs. At the same time, OA- and PA-induced total antioxidant capacity (TAC) levels in HLs were determined. Although especially low concentrations of OA (IC50=109.94 mg/L) and PA (IC50=665.49 mg/L) did not show cytotoxic effect at high levels in HLs, it was revealed that cytotoxicity was significantly (p<0.05) associated with oxidative stress and genotoxicity via correlation analysis. While TOS level in HLs did not statistically (p>0.05) increase in the presence of all treatments (0.5–100 mg/L) of PA, TAC level was increased by PA applications in certain concentrations (0.5–10 mg/L). Overall, the obtained data indicate that OA and especially PA as lichen compounds that do not cause oxidative stress can be a new resource of therapeutics as recognized in the present study with their high antioxidant features.

Toxicity assessment of hydroxyapatite nanoparticles in rat liver cell model in vitro

2016 ◽  
Vol 35 (10) ◽  
pp. 1073-1083 ◽  
Author(s):  
E Sonmez ◽  
I Cacciatore ◽  
F Bakan ◽  
H Turkez ◽  
YI Mohtar ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Model ◽  
Rat Hepatocytes ◽  
Toxicity Assessment ◽  
Control Culture ◽  
Hydroxyapatite Nanoparticles ◽  
Diphenyltetrazolium Bromide ◽  
Total Antioxidant ◽  
Total Oxidative Stress

Hydroxyapatite nanoparticles (HAP NPs) are widely used for preparations of biomedical and biotechnological fields such as drug delivery, gene therapy, and molecular imaging. However, the current toxicological knowledge about HAP NPs is relatively limited. The present study was designed to investigate the toxicity potentials of various concentrations (0–1000 µg cm−2) of HAP NPs in cultured primary rat hepatocytes. Cell viability was detected by 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) release, while total antioxidant capacity (TAC) and total oxidative stress (TOS) levels were determined to evaluate the oxidative injury. The DNA damage was also analyzed via scoring liver micronuclei rates and determining 8-oxo-2-deoxyguanosine (8-OH-dG) levels. The results of MTT and LDH assays showed that the higher concentrations of dispersed HAP NPs (300, 500, and 1000 µg cm−2) decreased cell viability. Also, HAP NPs increased TOS (500 and 1000 µg cm−2) levels and decreased TAC (300, 500, and 1000 µg cm−2) levels in cultured hepatocytes. On the basis of increasing doses, the NPs as depending on dose caused significant increases of the number of micronucleated hepatocytes and 8-OH-dG levels as compared to control culture. Furthermore, the highest concentration of HAP NPs (1000 µg cm−2) exhibited cytotoxic activity. Based on these results, HAP NPs have a dose-dependent toxic effect in rat hepatocytes. Further extensive research in this field is promising and reasonable.

scholarly journals In vitro cytotoxicity of Aspilia pluriseta Schweinf. extract fractions

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Sospeter N. Njeru ◽  
Jackson M. Muema
Keyword(s):  
Biological Activities ◽  
Vero Cells ◽  
In Vitro Cytotoxicity ◽  
Root Extract ◽  
Lack Of Information ◽  
Information Gap ◽  
Diphenyltetrazolium Bromide ◽  
Potential Use

Abstract Objectives We and others have shown that Aspilia pluriseta is associated with various biological activities. However, there is a lack of information on its cytotoxicity. This has created an information gap about the safety of A. pluriseta extracts. As an extension to our recent publication on the antimicrobial activity and the phytochemical characterization of A. pluriseta root extracts, here we report on cytotoxicity of tested solvent fractions. We evaluated the potential cytotoxicity of these root extract fractions on Vero cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results We show that all solvent extract fractions (except methanolic solvent fractions) had cytotoxic concentration values that killed 50% of the Vero cells (CC50) greater than 20 µg/mL and selectivity index (SI) greater than 1.0. Taken together, we demonstrate that, A. pluriseta extract fractions’ earlier reported bioactivities are within the acceptable cytotoxicity and selective index limits. This finding scientifically validates the potential use of A. pluriseta in the discovery of safe therapeutics agents.

scholarly journals The Effects of Taurine on Permethrininduced Cytogenetic and Oxidative Damage in Cultured Human Lymphocytes

2012 ◽  
Vol 63 (1) ◽  
pp. 27-34 ◽  
Author(s):  
Hasan Turkez ◽  
Elanur Aydin
Keyword(s):  
Oxidative Damage ◽  
Textile Industry ◽  
Human Lymphocytes ◽  
Sister Chromatid Exchanges ◽  
Dependent Manner ◽  
Beneficial Effects ◽  
Oxidative Damages ◽  
Total Oxidative Stress ◽  
Oxidative Effects

The Effects of Taurine on Permethrininduced Cytogenetic and Oxidative Damage in Cultured Human LymphocytesPermethrin (PM) is a common pyrethroid pesticide used to control pests in agriculture, forestry, horticulture, health care, homes, and textile industry. It is confirmed as a strong mutagen in animals and humans. Taurine (TA) is an amino acid found in mammalian tissues that protects the cell against DNA damage. In this study, we investigated whether supplementation of human lymphocyte cultures with TA (in the concentrations of 25 μg mL-1, 50 μg mL-1and 100 μg mL-1) provided any protection against PM toxicity applied in the concentration of 200 μg mL-1. Genotoxicity was assessed using the micronucleus (MN) and sister chromatid exchanges (SCE) tests. In addition, we measured the total antioxidant capacity (TAC) and total oxidative stress (TOS) levels in the plasma to determine oxidative effects. PM increased SCE and MN levels and altered TAC and TOS levels. TA alone did not affect SCE and MN levels compared to controls, regardless of the concentration applied. In addition, it increased TAC levels without changing TOS levels. Moreover, it significantly buffered the negative cytogenetic and oxidative effects induced by PM in a clear dose-dependent manner. In conclusion, this study is the first to evidence the beneficial effects of TA against PM-induced DNA and oxidative damagesin vitro.

PLEIOTROPIC EFFECT OF INTERLEUKIN-1 ON ENDOTHELIAL CELLS

1987 ◽  
Author(s):  
E Dejana ◽  
F Breviario ◽  
F Bussolino ◽  
L Mussoni ◽  
A Mantovani
Keyword(s):  
Leukocyte Adhesion ◽  
Biological Activities ◽  
Interleukin 1 ◽  
Platelet Activating Factor ◽  
Plasminogen Activator Inhibitor ◽  
Cell Types ◽  
Pleiotropic Effect ◽  
Neutrophil Adhesion ◽  
Structural Requirement

Inflammatory processes are often associated with pathological alteration of the vessel wall and sometimes with local or disseminated thrombotic phenomena. Interleukin-1 (IL-1), a monokine produced by activated cells of the monocyte/macrophage lineage and responsible of most of the changes associated with the inflammatory acute phase response, appears to dramatically' modify several endothelial cell (EC) functions. Some groups including ours (for review 1) have shown that IL-1 stimulates prostacyclin (PGI2), platelet activating factor (PAF), plasminogen activator inhibitor (PAi), thromboplastin (PCA) synthesis by cultured human EC in vitro. In addition IL-1 can act directly on EC to increase neuthophil and other leukocyte adhesion on their surface (2). All these effects, in contrast to previously described inducers, require a long time of interaction (30 min to 4 hours) of IL-1 with EC to be apparent and then last for several hours (4 to 12 hours). The IL-1 effects are concentration dependent (minimal active concentration being about 1 unit/ml) and require protein and RNA synthesis. To better define the structural requirement for IL-1 induced modification of EC functions we compared the activity of different IL-1 molecular species. Our approach is based on the observation that IL-1 is indeed a family of polypeptides biochemically different(3). At least two dissimilar gene products have been cloned with very limited homology (denominated α and β). These molecules, though biochemically different, share common activities and possibly the same receptor in different cell types. On EC we investigated whether the αand β IL-1 forms have similar biological activities (4). All the IL-1 preparations used were active on thymocyte costimulatory assay and comparison was made on the basis of the concentrations of these agents equally active on this assay.Human recombinant IL- αandβ (hr IL-1 α and hr IL-1 β) were both active in stimulating PGI2, PCA, PAi production and in increasing neutrophil adhesion to EC. In contrast PAF synthesis was Stimulated by hr IL-1 α but not by hr IL-1 β. Murine recombinant IL-1 (mr IL-1 α highly homologous with hr IL-1 < α, at concentrations able to maximally activate thymocytes was inactive on PGI2, PCA and in increasing neutrophil adhesion to EC. In contrast, mr IL-1 α was equally effective on PAF production as hr IL-1 α. A short peptide fragment of hr IL-1β (fragment 167-171) was synthesized on the basis of its predicted exposure on the surface of the molecule (5). This peptide is also located in a region (150-186) of high homology between hr IL-1α and β sequences. While the peptide showed high thymocyte activation capacity it was inactive on EC activities. Overall these results indicate that the α and β forms of human IL-1 elicit largely but not completely overlapping patterns of response in EC. In addition they suggest that the structural requirement for activation by IL-1 is not identical for thymocytes and EC. These results might provide some clues to novel strategies for modulation of IL-1 vascular and immunological activities.1. Mantovani A. and E. Dejana (1987) Biochem. Pharm. 36:301.2. Bevilacqua M. et al. (1985) J. Clin. Invest. 76:20033. Dinarello C.A. (1985) J. Clin. Immunol. 5:287.4. Dejana E. et al. (1987) Blood 69:695.5. Antoni G. et al. (1987) J. Immunol, (in press).

scholarly journals Cholesterol transporter ATP-binding cassette A1 (ABCA1) is elevated in prion disease and affects PrPC and PrPSc concentrations in cultured cells

2008 ◽  
Vol 89 (6) ◽  
pp. 1525-1532 ◽  
Author(s):  
Rajeev Kumar ◽  
Denise McClain ◽  
Rebecca Young ◽  
George A. Carlson
Keyword(s):  
Prion Disease ◽  
Cultured Cells ◽  
Prion Diseases ◽  
Neuroblastoma Cells ◽  
Direct Consequence ◽  
Brain Regions ◽  
Atp Binding ◽  
N2a Cells ◽  
Atp Binding Cassette

Prion diseases are transmissible neurodegenerative disorders of prion protein (PrP) conformation. Prion replication by conversion of benign PrPC isoforms into disease-specific PrPSc isoforms is intimately involved in prion disease pathogenesis and may be initiated in cholesterol-rich caveolae-like domains (CLD). Concentrations of the cholesterol transporter ATP-binding cassette A1 protein (ABCA1) are elevated in pre-clinical scrapie prion-infected mice and in prion-infected cells in vitro. Elevation of ABCA1 in prion-infected brain is not a direct consequence of local PrPSc accumulation, indeed levels of ABCA1 are comparable in brain regions that differ dramatically in the amount of PrPSc. Similarly, ABCA1 concentrations are identical in normal mice, transgenic mice overexpressing PrP and PrP knockout mice. In contrast, PrPC and PrPSc levels, but not Prnp mRNA, were increased by overexpression of ABCA1 in N2a neuroblastoma cells and scrapie prion-infected N2a cells (ScN2a). Conversely, RNAi-mediated knock down of Abca1 expression decreased the concentrations of PrPC in N2a cells and of PrPSc in ScN2a cells. These results suggest that ABCA1's effects on PrPC levels are post-translational and may reflect an increase in of PrPC stability, mediated either indirectly by increasing membrane cholesterol and CLD formation or by other functions of ABCA1. The increased supply of PrPC available for conversion would lead to increased PrPSc formation.

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