English E-Posta Öğrenci Bilgi Sistemi EBYS
FEN FAKÜLTESİ
Prof. Dr. Hasan TÜRKEZ
Prof. Dr. Hasan TÜRKEZ
Öğretim Üyesi
E-Posta :
hasanturkez@erzurum.edu.tr
Kişisel Sayfa :
Akademik Üniversite Fakülte Bölüm Ana Bilim Dalı Yıl
Doktora Atatürk Üniversitesi Fen Fakültesi Biyoloji 2007
Yrd. Doç. Atatürk Üniversitesi Fen Fakültesi Biyoloji 2007
Doçent Erzurum Teknik Üniversitesi Fen Fakültesi Moleküler Biyoloji ve Genetik 2011
Profesor Erzurum Teknik Üniversitesi Fen Fakültesi Moleküler Biyoloji ve Genetik 2016
Hizmet Süresi Kuruluş Pozisyon
Ödül Adı Kuruluş Yıl



Kuruluş Üyelik Türü Görev Hizmet Yılları
EACR Bilimsel Üye 2006 - ...
TIP ve BİYOLOJİ ALAN ÇALIŞMALARIM İÇİN LÜTFEN TIKLAYINIZ...
Yayınlar

1.
 2017 Oct;13(10):1089-1098. doi: 10.1080/17425255.2017.1375097. Epub 2017 Sep 10.

Genotoxicity testing: progress and prospects for the next decade.

Abstract

INTRODUCTION:

Genotoxicity and mutagenicity analyses have a significant role in the identification of hazard effects of therapeutic drugs, cosmetics, agrochemicals, industrial compounds, food additives, natural toxins and nanomaterials for regulatory purposes. To evaluate mutagenicity or genotoxicity, different in vitro and in vivo methodologies exert various genotoxicological endpoints such as point mutations, changes in number and structure of chromosomes. Areas covered: This review covered the basics of genotoxicity and in vitro/in vivo methods for determining of genetic damages. The limitations that have arisen as a result of the common use of these methods were also discussed. Finally, the perspectives of further prospects on the use of genotoxicity testing and genotoxic mode of action were emphasized. Expert opinion: The solution of actual and practical problems of genetic toxicology is inarguably based on the understanding of DNA damage mechanisms at molecular, subcellular, cellular, organ, system and organism levels. Current strategies to investigate human health risks should be modified to increase their performance for more reliable results and also new techniques such as toxicogenomics, epigenomics and single cell approaches must be integrated into genetic safety evolutions. The explored new biomarkers by the omic techniques will provide forceful genotoxicity assessment to reduce the cancer risk.

KEYWORDS:

Genetic toxicity; genotoxicity testing strategies; omics; risk assessment; short term assays

2.
 2017 Aug 30;109:402-411. doi: 10.1016/j.ejps.2017.08.030. [Epub ahead of print]

Memantine-derived drugs as potential antitumor agents for the treatment of glioblastoma.

Abstract

Glioblastoma is one of the most aggressive malignant primary brain cancer in adults. To date, surgery, radiotherapy and current pharmacological treatments are not sufficient to manage this pathology that has a high mortality rate (median survival 12-15months). Recently, anticancer multi-targeted compounds have attracted much attention with the aim to obtain new drugs able to hit different biological targets that are involved in the onset and progression of the disease. Here, we report the synthesis of novel memantine-derived drugs (MP1-10) and their potential antitumor activities in human U87MG glioblastoma cell line. MP1-10 were synthetized joining memantine, which is a NMDA antagonist, to different histone deacetylase inhibitors to obtain one molecule with improved therapeutic efficacy. Biological results indicated that MP1 and MP2 possessed more potent anti-proliferative effects on U87MG cells than MP3-10 in a dose-dependent manner. MP1 and MP2 induced significant cell death by apoptosis characterized by apoptotic morphological changes in Hoechst staining. Both drugs also exhibited non-genotoxic and only mild cytotoxic effects in human whole blood cells. However, only MP1, showing good chemico-physical properties (solubility, LogP) and enzymatic stabilities in gastric and intestinal fluids, can be considered a suitable candidate for in vivo pharmacokinetic studies.

KEYWORDS:

Glioblastoma; Histone deacetylase; Memantine; Mutual prodrug; PUBCHEM CID: Memantine hydrochloride 181458; PUBCHEM CID: Paclitaxel 36314

3.
 2017 Aug 1;273:257-265. doi: 10.1016/j.cbi.2017.06.027. Epub 2017 Jun 27.

Toxicogenomic responses of human alveolar epithelial cells to tungsten boride nanoparticles.

Abstract

During the recent years, microarray analysis of gene expression has become an inevitable tool for exploring toxicity of drugs and other chemicals on biological systems. Therefore, toxicogenomics is considered as a fruitful area for searching cellular pathways and mechanisms including cancer, immunological diseases, environmental responses, gene-gene interactions and chemical toxicity. In this work, we examined toxic effects of Tungsten Borides NPs on gene expression profiling of the human lung alveolar epithelial cells (HPAEpiC). In line with this purpose, a single crystal of tungsten boride (mixture of WB and W2B) nanoparticles was synthesized by means of zone melting method, and characterized via using X-ray crystallography (XRD), transmission electron microscope (TEM), scanning electron microscope (SEM) and energy-dispersive X-ray spectroscopy (EDX) techniques. Cell viability and cytotoxicity were determined by 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT), neutral red (NR) and lactate dehydrogenase (LDH) release tests. The whole genome microarray expression analysis was performed to find out the effects of WB and W2B NPs mixture on gene expression of the HPAEpiC cell culture. 123 of 40,000 gene probes were assigned to characterize expression profile for WB/W2B NPs exposure. According to results; 70 genes were up-regulated and 53 genes were down-regulated (≥2 fold change). For further investigations, these genes were functionally classified by using DAVID (The Database for Annotation, Visualization and Integrated Discovery) with gene ontology (GO) analysis. In the light of the data gained from this study, it could be concluded that the mixture of WB/W2B NPs can affect cytokine/chemokine metabolism, angiogenesis and prevent migration/invasion by activating various genes.

KEYWORDS:

Human lung alveolar epithelial cells; Microarray analysis; Toxicogenomics; Tungsten boride nanoparticles

PMID:
 
28666766
 
DOI:
 
10.1016/j.cbi.2017.06.027
[Indexed for MEDLINE]
Icon for Elsevier Science
4.
 2017 Jul 1;155:238-247. doi: 10.1016/j.colsurfb.2017.04.016. Epub 2017 Apr 12.

Nanoencapsulation strategies for the delivery of novel bifunctional antioxidant/σ1 selective ligands.

Abstract

Nowadays sigma-1 receptors are considered as new therapeutic objectives for central nervous system neurodegenerative diseases. Among different molecules, alpha lipoic acid has been identified as a natural potent antioxidant drug, whose therapeutic efficacy is limited by its many drawbacks, such as fast metabolism, poor bioavailability and high physico-chemical instability. Alfa-lipoic acid derivatives have been recently developed demonstrating their neuroprotective activity and effectiveness in different types of oxidative stress. In this work, two derivatives containing an amide or an ester functional group with different lipophilicity, were selected for their important affinity for sigma-1 receptors. Herein, in order to improve the in vitro stability and antioxidant effectiveness of alpha-lipoic acid derivatives, we focused our efforts in the nanoencapsulation strategies. Aqueous-core nanocapsules for the delivery of the hydrophilic compound and nanostructured lipid carrier for the lipophilic derivative, were properly designed and prepared using a direct or inverse eco-friendly organic solvent-free procedure. All nanosystems were characterized in terms of mean size, polydispersity, stability, morphology, encapsulation efficiency and in vitro release profiles. In order to evaluate the nanocarriers biocompatibility and antioxidant effectiveness, in vitro biological studies (cell viability, total antioxidant capacity and total oxidative status) were developed on primary human whole blood cell cultures, on both unloaded and derivatives-loaded nanodevices.

KEYWORDS:

Lipoic acid; NC; NLC; Nanoparticles; Nanotoxicity; Sigma receptors; Total antioxidant capacity; Total oxidant status; Turbiscan

5.
 2017 Jul;105(7):2056-2064. doi: 10.1002/jbm.a.35994. Epub 2017 May 17.

Molecular genetic and biochemical responses in human airway epithelial cell cultures exposed to titanium nanoparticles in vitro.

Abstract

Titanium nanoparticles (NPs) have very wide application areas such as paint, cosmetics, pharmaceuticals, and biomedical applications. And, to translate these nanomaterials to the clinic and industrial domains, their safety needs to be verified, particularly in terms of genotoxicity and cytotoxicity. Therefore, in this study, we aimed to investigate of cytotoxicity and changes in gene expression profiles influenced by commonly titanium (as titanium carbide, titanium carbo-nitride, titanium (II) oxide, titanium (III) oxide, titanium (IV) oxide, titanium nitride, titanium silicon oxide) NPs in human alveolar epithelial (HPAEpiC) and pharynx (HPPC) cell lines in vitro since inhalation is an important pathway for exposure to these NPs. HPAEpiC and HPPC cells were treated with titanium (0-100 µg/mL), NPs for 24 and 48 h, and then cytotoxicity was detected by, [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide] (MTT), uptake of neutral red (NR) and lactate dehydrogenase (LDH) release assays, while genotoxicity was also analyzed by cDNA array - RT-PCR assay. According to the results of MTT, NR and LDH assays, all tested NPs induced cytotoxicity on both HPAEpiC and HPPC cells in a time- and dose-dependent manner. Determining and analyzing the gene expression profiles of HPAEpiC and HPPC cells, titanium NPs showed more changes in genes related to DNA damage or repair, oxidative stress, and apoptosis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2056-2064, 2017.

KEYWORDS:

airway epithelial cell; genotoxicity; in vitro gene expression; nanotoxicity; titanium

6.
 2017 Jan 13;28(2):025102. Epub 2016 Dec 6.

Gold nanoparticles as scaffolds for poor water soluble and difficult to vehiculate antiparkinson codrugs.

Abstract

We report the facile and non-covalent preparation of gold nanoparticles (AuNPs) stabilized by an antiparkinson codrug based on lipoic acid (LA). The obtained AuNPs appear stable in both dimethyl sulfoxide and fetal bovine serum and able to load an amount of codrug double the weight of gold. These NPs were demonstrated to be safe and biocompatible towards primary human blood cells and human neuroblastoma cells, one of the most widely used cellular models to study dopaminergic neural cells, therefore are ideal drug carriers for difficult to solubilize molecules. Very interestingly, the codrug-stabilized AuNPs were shown to reduce the accumulation of reactive oxygen species in SH-SY5Y cells treated with LD and did not change total oxidant status levels in cultured human blood cells, thus confirming the antioxidant role of LA although bound to AuNPs. The characterization of AuNPs in terms of loading and stability paves the way for their use in biomedical and pharmacological applications.

7.
 2017;17(2):123-128. doi: 10.2174/1871524916666160625123621.

Synthesis and Antioxidant Properties of Novel Memantine Derivatives.

Abstract

BACKGROUND:

Medicinal chemistry methodologies are presently used to develop multifunctional molecules which simultaneously reduce oxidative stress, excitotoxicity, metal dyshomeostasis, and neuroinflammation that characterize neuropathological conditions, such as Alzheimer's Disease.

RESULTS:

Memantine (MEM) derivatives 1-6 were designed and synthesized as novel multifunctional entities with antioxidant and neuroprotective capabilities to manage neurodegenerative diseases, such as Alzheimer's Disease. In vitro neuroprotective studies were performed by using astroglial GL15 cell line to assess antioxidant capability of MEM derivatives 1-6.

CONCLUSION:

Our outcomes showed that compounds 1 and 5 (at the concentration of 10 μM), containing as antioxidant portion residues of N-acetyl-Cys-OH and N-acetyl-Cys(Allyl)-OH, respectively, revealed a significant neuroprotective activity against oxidative stress, as assessed by NBT assays.

KEYWORDS:

Alzheimer's disease; MEM; NMDA antagonist; S-Allylcysteine; cysteine derivatives; neuroprotective

8.
 2016 Jul 15;24(14):3149-56. doi: 10.1016/j.bmc.2016.05.045. Epub 2016 May 21.

New bifunctional antioxidant/σ1 agonist ligands: Preliminary chemico-physical and biological evaluation.

Abstract

We previously reported bifunctional sigma-1 (σ1) ligands endowed with antioxidant activity (1 and 2). In the present paper, pure enantiomers (R)-1 and (R)-2 along with the corresponding p-methoxy (6, 11), p-fluoro derivatives (7, 12) were synthesized. σ1 and σ2 affinities, antioxidant properties, and chemico-physical profiles were evaluated. Para derivatives, while maintaining strong σ1 affinity, displayed improved σ1 selectivity compared to the parent compounds 1 and 2. In vivo evaluation of compounds 1, 2, (R)-1, 7, and 12 showed σ1 agonist pharmacological profile. Chemico-physical studies revealed that amides 2, 11 and 12 were more stable than corresponding esters 1, 6 and 7 under our experimental conditions. Antioxidant properties were exhibited by fluoro derivatives 7 and 12 being able to increase total antioxidant capacity (TAC). Our results underline that p-substituents have an important role on σ1 selectivity, TAC, chemical and enzymatic stabilities. In particular, our data suggest that new very selective compounds 7 and 12 could be promising tools to investigate the disorders in which σ1 receptor dysfunction and oxidative stress are contemporarily involved.

KEYWORDS:

Antioxidants; Chemical and enzymatic stabilities; Lipoic acid; Neuroprotection; Oxidative stress; σ(1) receptors

PMID:
 
27262426
 
DOI:
 
10.1016/j.bmc.2016.05.045
[Indexed for MEDLINE]
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9.
 2016 Sep;54(9):1748-62. doi: 10.3109/13880209.2015.1126620. Epub 2015 Dec 24.

In vitro antitumor activities of the lichen compounds olivetoric, physodic and psoromic acid in rat neuron and glioblastoma cells.

Abstract

Context Since methods utilised in the treatment of glioblastoma multiforme (GBM) are inadequate and have too many side effects, usage of herbal products in the treatment process comes into prominence. Lichens are symbiotic organisms used for medicinal purposes for many years. There are various anticancer treatments about components of two lichen species used in the present study. Objective Antitumor potential of three lichen secondary metabolites including olivetoric acid (OLA) and physodic acid (PHA) isolated from Pseudevernia furfuracea (L.) Zopf (Parmeliaceae) and psoromic acid (PSA) isolated from Rhizoplaca melanophthalma (DC.) Leuckert (Lecanoraceae) were investigated on human U87MG-GBM cell lines and primary rat cerebral cortex (PRCC) cells for the first time. Materials and methods PRCC cells used as healthy brain cells were obtained from Sprague-Dawley rats. The treatments were carried out on the cells cultured for 48 h. Cytotoxic effects of different concentrations (2.5, 5, 10, 20 and 40 mg/L) of metabolites on the cells were determined via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) analyses. Total antioxidant capacity (TAC) and total oxidant status (TOS) parameters were used for assessing oxidative alterations. Oxidative DNA damage potentials of metabolites were investigated via evaluating 8-hydroxy-2'-deoxyguanosine (8-OH-dG) levels. Results Median inhibitory concentration (IC50) values of OLA, PHA and PSA were 125.71, 698.19 and 79.40 mg/L for PRCC cells and 17.55, 410.72 and 56.22 mg/L for U87MG cells, respectively. It was revealed that cytotoxic effects of these metabolites showed positive correlation with concentration, LDH activity and oxidative DNA damage. Discussion and conclusion The present findings obtained in this study revealed that primarily OLA and then PSA had high potential for use in the treatment of GBM.

KEYWORDS:

Cytotoxicity; genotoxicity; glioblastoma multiforme; oxidative status; secondary metabolite

PMID:
 
26704132
 
DOI:
 
10.3109/13880209.2015.1126620
[Indexed for MEDLINE]
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10.
 2016 Oct;35(10):1073-83. doi: 10.1177/0960327115619770. Epub 2015 Dec 11.

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

Abstract

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.

KEYWORDS:

Hydroxyapatite nanoparticles; cytotoxicity; genotoxicity; oxidative stress; rat hepatocytes

PMID:
 
26655636
 
DOI:
 
10.1177/0960327115619770
[Indexed for MEDLINE]
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11.
 2016 Jun;32(6):1074-85. doi: 10.1177/0748233714547382. Epub 2014 Sep 3.

Ameliorative effects of docosahexaenoic acid on the toxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in cultured rat hepatocytes.

Abstract

The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant toxicant that mediates carcinogenic effects associated with oxidative DNA damage. Docosahexaenoic acid (DHA) with antioxidant functions has many biochemical, cellular, and physiological functions for cells. The present study assessed, for the first time, the ameliorative effect of DHA in alleviating the toxicity of TCDD on primary cultured rat hepatocytes (HEPs). In vitro, isolated HEPs were incubated with TCDD (5 and 10 μM) in the presence and absence of DHA (5, 10, and 20 μM) for 48 h. The cell viability was detected by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) release. DNA damage was analyzed by liver micronucleus assay and 8-oxo-2-deoxyguanosine (8-OH-dG) level. In addition, total antioxidant capacity (TAC) and total oxidative stress (TOS) were assessed to determine the oxidative injury in HEPs. The results of MTT and LDH assays showed that TCDD decreased cell viability but not DHA. On the basis of increasing treatment concentrations, the dioxin caused significant increases of micronucleated HEPs and 8-OH-dG as compared to control culture. TCDD also led to significant increases in TOS content. On the contrary, in cultures treated with DHA, the level of TAC was significantly increased during treatment in a concentration-dependent fashion. DHA showed therapeutic potential against TCDD-mediated cell viability and DNA damages. As conclusion, this study provides the first evidence that DHA has protective effects against TCDD toxicity on primary cultured rat hepatocytes.

KEYWORDS:

2; 3; 7; 8-oxo-2-deoxyguanosine; 8-tetrachlorodibenzo-p-dioxin; Docosahexaenoic acid; antioxidant capacity; cell viability; liver; micronucleus assay; oxidative stress; rat

PMID:
 
25187318
 
DOI:
 
10.1177/0748233714547382
[Indexed for MEDLINE]
Icon for Atypon
12.
 2016 Mar;68(2):291-302. doi: 10.1007/s10616-014-9780-6. Epub 2014 Aug 23.

Health risk assessments of lithium titanate nanoparticles in rat liver cell model for its safe applications in nanopharmacology and nanomedicine.

Abstract

Due to their high chemical stability, lithium titanate (Li2TiO3) nanoparticles (LTT NPs) now are projected to be transferred into different nanotechnology areas like nano pharmacology and nano medicine. With the increased applications of LTT NPs for numerous purposes, the concerns about their potential human toxicity effects and their environmental impact are also increased. However, toxicity data for LTT NPs related to human health are very limited. Therefore we aimed to investigate toxicity potentials of various concentrations (0-1,000 ppm) of LTT NPs (<100 nm) 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. DNA damage was analyzed by scoring liver micronuclei rates and by determining 8-oxo-2-deoxyguanosine (8-OH-dG) levels. The results of MTT and LDH assays showed that higher concentrations of dispersed LTT NPs (500 and 1,000 ppm) decreased cell viability. Also, LTT NPs increased TOS (300, 500 and 1,000 ppm) levels and decreased TAC (300, 500 and 1,000 ppm) levels in cultured hepatocytes. The results of genotoxicity tests revealed that LTT NPs did not cause significant increases of micronucleated hepatocytes and 8-OH-dG as compared to control culture. In conclusion, the obtained results showed for the first time that LTT NPs had dose dependent effects on oxidative damage and cytotoxicity but not genotoxicity in cultured primary rat hepatocytes for the first time.

KEYWORDS:

Cytotoxicity; Genotoxicity; Lithium titanate nanoparticles; Oxidative stress; Rat Hepatocytes

PMID:
 
25149287
 
PMCID:
 
PMC4754244
 [Available on 2017-03-01]
 
DOI:
 
10.1007/s10616-014-9780-6
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13.
 2015 May;67(3):409-18. doi: 10.1007/s10616-014-9698-z. Epub 2014 Mar 4.

Genotoxic and oxidative damage potentials in human lymphocytes after exposure to terpinolene in vitro.

Abstract

Terpinolene (TPO) is a monocyclic monoterpene found in the essential oils of various fir and pine species. Recent reports indicated that several monoterpenes could exhibit antioxidant effects in both human and animal experimental models. However, so far, the nature and/or biological roles of TPO have not been elucidated in human models yet. The aim of this study was to investigate the genetic, oxidative and cytotoxic effects of TPO in cultured human blood cells (n = 5) for the first time. Human blood cells were treated with TPO (0-200 mg/L) for 24 and 48 h, and then cytotoxicity was detected by lactate dehydrogenase (LDH) release and [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay, while DNA damage was also analyzed by micronucleus assay, sister chromatid exchanges assay and 8-oxo-2-deoxyguanosine (8-OH-dG) level. In addition, biochemical parameters [total antioxidant capacity (TAC) and total oxidative stress (TOS)] were examined to determine oxidative effects. The results of LDH and MTT assays showed that TPO (at concentrations greater than 100 mg/L) decreased cell viability. In our in vitro test systems, it was observed that TPO had no genotoxicity on human lymphocytes. Again, TPO (at 10, 25, 50 and 75 mg/L) treatment caused statistically important (p < 0.05) increases of TAC levels in human lymphocytes without changing TOS levels. In conclusion, TPO can be a new resource of therapeutics as recognized in this study with its non-genotoxic and antioxidant features.

14.
 2014 Apr;34(4):373-9. doi: 10.1002/jat.2958. Epub 2013 Nov 6.

Evaluation of cytotoxic, oxidative stress and genotoxic responses of hydroxyapatite nanoparticles on human blood cells.

Abstract

The present study was designed to investigate genotoxic and cytotoxic effects and oxidative damage of increasing concentrations of nano-hydroxyapatite (5, 10, 20, 50, 75, 100, 150, 300, 500 and 1000 ppm) in primary human blood cell cultures. Cell viability was detected by [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide] assay and lactate dehydrogenase release, while total antioxidant capacity and total oxidative stress levels were determined to evaluate the oxidative injury. The DNA damage was also analyzed by sister chromatid exchange, micronuclei, chromosome aberration assays and 8-oxo-2-deoxyguanosine level as indicators of genotoxicity. The results of [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide] and lactate dehydrogenase assays showed that the higher concentrations (150, 300, 500 and 1000 ppm) of hydroxyapatite nanoparticles (HAP NPs) decreased cell viability. HAP NPs led to increases of total oxidative stress (300, 500 and 1000 ppm) levels and decreased total antioxidant capacity (150, 300, 500 and 1000 ppm) levels in cultured human blood cells. On the basis of increasing concentrations, HAP NPs caused significant increases of sister chromatid exchange, micronuclei, chromosome aberration rates and 8-oxo-2-deoxyguanosine levels as compared to untreated culture. In conclusion, the obtained in vitro results showed that HAP NPs had dose-dependent effects on inducing oxidative damage, genotoxicity and cytotoxicity in human blood cells.

KEYWORDS:

Cytotoxicity; Genotoxicity; Hydroxyapatite; Lymphocyte; Oxidative stress

PMID:
 
24474238
 
DOI:
 
10.1002/jat.2958
[Indexed for MEDLINE]
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15.
 2016 Apr;32(4):625-33. doi: 10.1177/0748233713506771. Epub 2013 Nov 8.

Investigation of cytotoxic, genotoxic and oxidative properties of carvacrol in human blood cells.

Abstract

Carvacrol (CVC), a major constituent of genera Origanum and Thymus, is such a substance that has attracted attention because of its wide variety of beneficial biological activities such as antibacterial, antifungal, and anticancer effects. However, there are limited data on the cytogenetic and antioxidant effects of CVC in cultured human blood cells. The aim of this study was to investigate for the first time the genetic, oxidative, and cytotoxic effects of CVC in cultured human blood cells (n= 5). Human blood cells were treated with CVC (0-200 mg/L) for 24 and 48 h and then cytotoxicity detected by lactate dehydrogenase (LDH) release and (3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide) (MTT) assay, while DNA damage was also analyzed by micronucleus (MN) assay, chromosomal aberration (CA) assay and 8-oxo-2-deoxyguanosine (8-OH-dG) level. In addition, biochemical parameters (total antioxidant capacity [TAC] and total oxidative stress [TOS]) were examined to determine the oxidative effects. The results of LDH and MTT assays showed that CVC (at concentrations above 100 mg/L) decreased cell viability. In our in vitro test systems, it was observed that CVC had no mutagenic effects on human lymphocytes. On the other hand, CVC (at 50, 75, and 100 mg/L) treatment caused statistically important (p< 0.05) increases in TAC and TOS levels (at 150 and 200 mg/L) on human lymphocytes. In conclusion, CVC can be a new resource of therapeutics as recognized in this study with their nonmutagenic and antioxidant features.

KEYWORDS:

Carvacrol; cytotoxicity; genotoxicity; human lymphocytes; oxidative effects

PMID:
 
24215060
 
DOI:
 
10.1177/0748233713506771
[Indexed for MEDLINE]
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16.
 2014 Jan;34(1):101-11. doi: 10.1007/s10571-013-9991-y. Epub 2013 Oct 9.

Neuroprotective effects of farnesene against hydrogen peroxide-induced neurotoxicity in vitro.

Abstract

Oxidative stress is highly damaging to cellular macromolecules and is also considered a main cause of the loss and impairment of neurons in several neurodegenerative disorders. Recent reports indicate that farnesene (FNS), an acyclic sesquiterpene, has antioxidant properties. However, little is known about the effects of FNS on oxidative stress-induced neurotoxicity. We used hydrogen peroxide (H2O2) exposure for 6 h to model oxidative stress. Therefore, this experimental design allowed us to explore the neuroprotective potential of different FNS isomers (α-FNS and β-FNS) and their mixture (Mix-FNS) in H2O2-induced toxicity in newborn rat cerebral cortex cell cultures for the first time. For this aim, both MTT and lactate dehydrogenase assays were carried out to evaluate cell viability. Total antioxidant capacity (TAC) and total oxidative stress (TOS) parameters were used to assess oxidative alterations. In addition to determining of 8-hydroxy-2-deoxyguanosine (8-OH-dG) levels in vitro, the comet assay was also performed for measuring the resistance of neuronal DNA to H2O2-induced challenge. 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 (comet assay) increased in the group treated with H2O2 alone. But pretreatment of FNS suppressed the cytotoxicity, genotoxicity and oxidative stress, which were increased by H2O2 in clear type of isomers and applied concentration-dependent manners. The order of antioxidant effectiveness for modulating H2O2-induced oxidative stress-based neurotoxicity and genotoxicity is as β-FNS > Mix-FNS > α-FNS.

PMID:
 
24105026
 
DOI:
 
10.1007/s10571-013-9991-y
[Indexed for MEDLINE]
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17.
 2013 Sep 3;18(9):10747-67. doi: 10.3390/molecules180910747.

New flurbiprofen derivatives: synthesis, membrane affinity and evaluation of in vitro effect on β-amyloid levels.

Abstract

Alzheimer's disease (AD) is characterized by irreversible and progressive loss of memory and cognition and profound neuronal loss. Current therapeutic strategies for the treatment of AD have been directed to a variety of targets with the aim of reversing or preventing the disease but, unfortunately, the available treatments often produce no significant clinical benefits. During the last decades compounds that inhibit or modulate γ-secretase, reducing β amyloid (Aβ) levels, have been considered as potential therapeutics for AD. Among these the (R)-enantiomer of flurbiprofen (FLU) seems to be very promising, but it shows low brain penetration. In this study, in order to improve the properties of FLU against Alzheimer's pathogenesis we synthesized some novel FLU lipophilic analogues. Lipophilicity of the new molecules has been characterized in terms of clogP, log K(C18/W) and log K(IAM/W) values. Permeability has been determined in both gastrointestinal PAMPA (PAMPA-GI) at different pH values and in brain blood barrier PAMPA (PAMPA-BBB) models. They were also tested for their ability to inhibit in vitro γ-secretase activity using rat CTXTNA2 astrocytes. Interestingly, the investigated molecules demonstrated to reduce Aβ 42 levels without affecting the amyloid precursor protein APP level in a clear concentrations-dependent manner.

PMID:
 
24005968
 
DOI:
 
10.3390/molecules180910747
[Indexed for MEDLINE] 
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18.
 2013 Oct;29(9):775-9. doi: 10.1177/0748233712442739. Epub 2012 Apr 4.

Borax counteracts genotoxicity of aluminum in rat liver.

Abstract

This study was carried out to evaluate the protective role of borax (BX) on genotoxicity induced by aluminum (Al) in rat liver, using liver micronucleus assay as an indicator of genotoxicity. Sprague-Dawley rats were randomly separated into six groups and each group had four animals. Aluminum chloride (AlCl₃; 5 mg/kg b.w.) and BX (3.25 and 13 mg/kg b.w.) were injected intraperitoneally to rats. Besides, animals were also treated with Al for 4 consecutive days followed by BX for 10 days. Rats were anesthetized after Al and BX injections and the hepatocytes were isolated for counting the number of micronucleated hepatocytes (MNHEPs). AlCl₃ was found to significantly (p < 0.05) increase the number of MNHEPs. Rats treated with BX, however, showed no increase in MNHEPs. Moreover, simultaneous treatments with BX significantly modulated the genotoxic effects of AlCl₃ in rats. It can be concluded that BX has beneficial influences and has the ability to antagonize Al toxicity.

KEYWORDS:

Aluminum; borax; in vivo; liver; micronucleus assay; rat

PMID:
 
22491726
 
DOI:
 
10.1177/0748233712442739
[Indexed for MEDLINE]
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19.
 2012 Jun;50(6):2142-8. doi: 10.1016/j.fct.2011.09.018. Epub 2011 Sep 19.

Propolis protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced toxicity in rat hepatocytes.

Abstract

The present experiment was undertaken to determine the effectiveness of propolis in alleviating the toxicity of TCDD on cultured primary rat hepatocytes. Propolis (25, 50 and 100 μM) was added to plain culture or simultaneously with TCDD (5 and 10 μM). The hepatocytes were treated with TCDD and propolis for 48 h. Then 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 by liver micronucleus assay (LMN) and 8-oxo-2-deoxyguanosine (8-OH-dG). The results of MTT and LDH assays showed that TCDD decreased cell viability. TCDD also increased TOS level and decreased TAC level in rat hepatocytes. On the basis of increasing doses, the TCDD caused significant increases of micronucleated hepatocytes (MNHEPs) and 8-OH-dG levels as compared to control culture. In cultures treated with propolis alone, cell viability and TOS level were not affected, while the level of TAC was significantly increased in dose-dependent fashion. The presence of propolis with TCDD modulated its toxic effects on primary hepatocytes cultures. Noteworthy, propolis has a protective effect against TCDD-mediated DNA damages.

PMID:
 
21963951
 
DOI:
 
10.1016/j.fct.2011.09.018
[Indexed for MEDLINE]
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20.
 2012 Jan;64(1-2):93-101. doi: 10.1016/j.etp.2010.06.011. Epub 2010 Jul 20.

The effects of some boron compounds against heavy metal toxicity in human blood.

Abstract

Heavy metals can accumulate in the environment and cause serious damages to ecosystems and human health. Boron is considered to be essential micronutrient with its well established biological functions and the antioxidant effects of boric acid (BA) are controversial. However, the potential of important boron compounds in cellular activities remains unexplored. Therefore, we aimed to assess the efficacies of some boron compounds (BA, borax, colemanite and ulexite) on the genotoxicity induced by heavy metals (arsenic trioxide, colloidal bismuth subcitrate, cadmium chloride, mercury chloride and lead chloride) in human blood cultures. For this aim, sister chromatid exchange (SCE) and micronuclei (MN) assays were performed to establish DNA damages in lymphocytes. Besides, oxidative stress was monitored by estimating the changes of main antioxidant enzyme activities and the levels of total glutathione (TGSH) in erythrocytes. The present study showed that heavy metal treatments increased the frequencies of SCE and MN and the plasma malondialdehyde (MDA) level; decreased the antioxidant enzyme activities and the level of TGSH compared to controls. Whereas, the tested boron compounds (5-20 ppm) significantly reduced the genotoxic effects induced by low doses of heavy metals. Our results revealed that the protective roles of boron compounds occurred with the effectiveness on their anti-oxidant capacity. In conclusion, these compounds could be useful in the development of functional food and raw materials of medicine.

PMID:
 
20663653
 
DOI:
 
10.1016/j.etp.2010.06.011
[Indexed for MEDLINE]
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Erzurum Teknik Üniversitesi bünyesinde 2010 yilinda kurulan Fen Fakültemiz, yeni ve öncü olmanin verdigi heyecan ve avantajlarla egitim ögretim hayatina.. DEVAM

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