Browsing by Author "Turkez, Hasan"

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Antioxidant Potential of Ulexite in Zebrafish Brain: Assessment of Oxidative Dna Damage, Apoptosis, and Response of Antioxidant Defense System
(Springernature, 2021) Alak, Gonca; Ucar, Arzu; Parlak, Veysel; Yeltekin, Asli Cilingir; Ozgeris, Fatma Betul; Atamanalp, Muhammed; Turkez, Hasan
In recent years, because of its significant biological roles, the usage of boron has been started in animal feeding. In this research, it was aimed to investigate the ulexite's action mechanism on the zebrafish brain with an evaluation of the oxidative parameters. The adult zebrafish were exposed to four ulexite doses (5, 10, 20, and 40 mg/l) in a static test apparatus for 96 h. For assessing the oxidative responses, multiple biochemical analyses were performed in brain tissues. The results indicated the supporting potential of low ulexite doses on the antioxidant system (< 40 mg/l) and that low-dose ulexite does not lead to oxidative stress in the zebrafish brain. Again, our results showed that low ulexite concentrations did not cause DNA damage or apoptosis. As a final result, in aquatic environments, ulexite (a boron compound) can be used in a safe manner, but it would be useful at higher concentrations to consider the damages of the cells that are probable to develop because of the oxidative stress
Assesment of Hematotoxic, Oxidative and Genotoxic Damage Potentials of Fipronil in Rainbow Trout Oncorhynchus Mykiss, Walbaum
(Taylor & Francis Ltd, 2021) Ucar, Arzu; Parlak, Veysel; Cilingir Yeltekin, Asli; Ozgeris, Fatma Betul; Caglar, Ozge; Turkez, Hasan; Atamanalp, Muhammed
In this study, changes in the blood tissue of rainbow trout (Oncorhynchus mykiss, Walbaum, 1792) caused by Fipronil (FP) insecticide were investigated using different biomarkers (Hematology parameters, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), malondialdehyde (MDA), paraoxonase (PON), arylesterase (ARE), myeleperoxidase (MPO), micronucleus (MN), 8-hydroxy-2-deoxyguanosine (8-OHdG)) level and caspase-3 activity. Statistically significant alterations in hematology parameters occurred with FP effect. In blood tissue, dose-dependent inhibition was determined in SOD-CAT-GPX-PON and ARE enzyme activities, but MDA and MPO were induced statistically significant. The results of MN assay were compared with the control group and it was obtained that genotoxicity of different dose groups was similar. The level of 8-OHdG and the activity and caspase-3 examined in blood tissue was increased depending on the dose. It was determined with different biomarkers that this insecticide caused physiological stress changes in the tissues examined.
Borax Alleviates Copper-Induced Renal Injury Via Inhibiting the Dna Damage and Apoptosis in Rainbow Trout
(Springernature, 2019) Alak, Gonca; Yeltekin, Asli Cilingir; Ucar, Arzu; Parlak, Veysel; Turkez, Hasan; Atamanalp, Muhammed
The aim of this study was to determine the therapeutic potential of borax against copper in the kidney tissue of the rainbow trout fed with added borax (BX) (1.25, 2.5, and 5 mg/kg) and/or copper (Cu) (500,1000 mg/kg) contents. For this purpose, two treatment groups had designed, and glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) enzyme activities were determined. Besides, oxidative DNA damage (8-hydroxy-2 '-deoxyguanosine, 8-OHdG), caspase-3, and malondialdehyde (MDA) levels were assessed in kidneys of all treatment groups. In molecular pathway, hsp70, CYP1A, and antioxidant gene expression levels were determined. In the results of the analysis, antioxidant enzyme activity and gene expression were increased; 8-OHdG, caspase-3, and MDA levels were decreased in groups fed with borax supplemented feeds compared to the copper-treated group. The alterations among the groups were found as significant (p < 0.05). CYP1A and hsp70 gene expressions were upregulated in copper and copper combined groups (p < 0.05). The findings of present research showed that borax had alleviative effect on copper-induced toxicity and could be used as an antidote in fish nutrition.
Borax Attenuates Oxidative Stress, Inflammation, and Apoptosis by Modulating Nrf2/Ros Balance in Acrylamide-Induced Neurotoxicity in Rainbow Trout
(Taylor & Francis Ltd, 2025) Turkez, Hasan; Alak, Gonca; Ozgeris, Fatma Betul; Cilingir Yeltekin, Asli; Ucar, Arzu; Parlak, Veysel; Atamanalp, Muhammed
Acrylamide (ACR) can have adverse environmental effects because of its multiple applications. Relevant scientific literatures of the existence of ACR residues in foods following processing steps have raised concern in the biochemistry, chemistry and safety of this vinyl substance. The interest has focused on the hepatotoxicity of ACR in animals and humans and on the ACR content mitigation and its detoxification. Borax (BX), as a naturally occurring antioxidant featured boron compound, was selected in this investigation to assess its possible neuro-protective potential against ACR-induced neurotoxicity. Nrf2 axis signaling pathways and detoxification response to oxidative stress after exposure to ACR in brains of rainbow trout, and the effect of BX application on reducing ACR-induced neurotoxicity were investigated. Rainbow trout were acutely exposed to ACR (12.5 mg/L) alone or simultaneously treated with BX (0.75 mg/L) during 96h. The exposed fish were sampled at 48th and 96th and oxidative stress response endpoints, 8-OHdG, Nrf2, TNF-alpha, caspase-3, in addition to IL-6 activities and the levels of AChE and BDNF in brain tissues of rainbow trout (Oncorhynchus mykiss) were evaluated. Samples showed decreases in the levels of ACR-mediated biomarkers used to assess neural toxicity (SOD, CAT, GPx, AChE, BDNF, GSH), increased levels of MDA, MPO, DNA damage and apoptosis. ACR disrupted the Nrf2 pathway, and induced neurotoxicity. Inhibited activities' expressions under simultaneous administration experiments, revealed the protective effects of BX against ACR-induced toxicity damage. The obtained data allow the outline of early multi-parameter signaling pathways in rainbow trout
Borax Exerts Protective Effect Against Ferrocene-Induced Neurotoxicity in Oncorhynchus Mykiss
(Elsevier Gmbh, 2022) Yeltekin, Ash Cilingir; Ucar, Arzu; Parlak, Veysel; Ozgeris, Fatma Betul; Turkez, Hasan; Esenbuga, Nurinisa; Alak, Gonca
Background: In recent years, therapeutic targets and the development of new drugs have shifted research towards inflammatory and oxidative stress pathways. Ferrocene (FcH) is a stable, small molecule that exhibits immunostimulatory and anti-tumor properties by a different mechanism and is effective at low doses in oral administration. However, it was surprising that there has been no performed investigation using FcH on aquaculture. On the other hand, recent papers reveal the key biological functions and health benefits due to daily boron intake in animals and humans. Therefore, we investigated the neurotoxic damage potential of FcH and its related neurotoxicity action mechanism in aquatic environments. In addition, the protective potential of borax (BX, or sodium borate) were evaluated againt in vivo neurotoxicity by FcH. Methods: Neurotoxicity assessment was performed in rainbow trout brain tissue, acutely under semi-static conditions via determining a vide range of parameters including catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) activities as well as glutathione (GSH), myeloperoxidase (MPO), glutathione (GSH), malondialdehyde (MDA levels), DNA damage (8-OHdG), apoptosis (caspase 3), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), nuclear factor erythroid-2 (Nrf-2), acetylcholinesterase (AChE) and brain-derived neurotrophic factor (BDNF) levels. In addition, the LC50 96 h level of FcH was determined for the first time in rainbow trout in this study. Results: In the obtained results, while FcH caused inhibition in enzyme activities, it showed an inducing effect on MDA, MPO, BDNF, Nrf2, TNF-alpha and IL-6 levels. It was determined that this oxidative damage related alterations were significantly different (p < 0.05) in comparison between FcH treated and controls. Again, the LC 50 96 h value in rainbow trout was determined as 11.73 mg/L, which is approximately 5% less than the value given for freshwater fish (12.3 mg/L). On the contrary, it was observed that BX has a mitigating effect on FcH-induced neurotoxicity. Conclusion: The present study suggests that borax may be useful for preventing or alleviating neurotoxicity induced by environmental contaminants or toxic chemicals.
Borax Relieved the Acrylamide-Induced Hematotoxic, Hepatotoxic, Immunotoxic and Genotoxic Damages in Rainbow Trout by Regulating Apoptosis and Nrf2 Signaling Pathway
(Elsevier Science inc, 2022) Atamanalp, Muhammed; Turkez, Hasan; Yeltekin, Asli cilingir; Ozgeris, Fatma Betuel; Ucar, Arzu; caglar, Ozge; Alak, Gonca
Acrylamide(AA) is a compound with wide usage areas including paper, dyes, and plastics industries. Due to its broad spectrum and water solubility suggest that this vinyl compound may cause serious environmental problems. AA was shown to exhibit neurotoxic, immunotoxic, reproductive toxicant as well as carcinogenic potency on animals. Especially in recent years, the therapeutic effects of boron and boron containing compounds like borax(BX), ulexite(ULX) and colemanite(COL) had been reported. However, the ameliorative potential by boron compounds against AA-induced toxicities had not been investigated yet. Therefore, in this investigation rainbow trout were exposed acutely to AA in the presence and absence of BX. The hematological indices and genotoxic end-points were examined in the fish blood tissue. In addition to oxidative stress response, the levels of DNA damage, CASP3, TNF-alpha, Nrf-2 as well as IL-6 amounts were determined in both blood and liver tissues of fish. The obtained results executed that AA induced toxic conditions in both tissues. In fact, an increase in the amount of oxidative stress and ROS, and a decrease in GSH levels were observed. AA exposure led to an increase in CASP3levels and 8-OHdG formation. It was also found that Nrf-2 pathway contributed to the initiation of oxidative stress that associated with AA-induced toxicity. On the contrary, our findings indicated that co-exposure of BX with AA elicited oxidative stress and cell death. In a conclusion BX was suggested as a useful and effective natural agent for the prevention and early treatment of AA toxicity in fish.
Effects of Two Lichen Acids Isolated From Pseudevernia Furfuracea (L.) Zopf in Cultured Human Lymphocytes
(Walter de Gruyter Gmbh, 2018) Emsen, Bugrahan; Togar, Basak; Turkez, Hasan; Aslan, Ali
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.
In Vitro Evaluation of Selective Cytotoxic Activity of Chaerophyllum Macropodum Boiss. on Cultured Human Sh-Sy5y Neuroblastoma Cells
(Springer, 2022) Celikezen, Fatih Caglar; Turkez, Hasan; Firat, Mehmet; Arslan, Mehmet Enes; Oner, Sena
Neuroblastoma is the most common solid tumor in children. New treatment approaches are needed because of the harmful side effects and costs of the methods used in the treatment of neuroblastoma. Medicinal and aromatic plants are important for new treatment approaches due to their minimal side effects and economic advantages. Therefore, the present study was carried out to examine the cytotoxic effect of Chaerophyllum macropodum extract on human neuroblastoma (SH-SY5Y) and fibroblast (HDFa) cell lines. 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase release (LDH) assays were used to determine the cytotoxic effect of C. macropodum. The extracts were analyzed for their phenolic content by HPLC-PDA. Major components were determined as 63.600% o-coumaric acid, 15.606% catechine hydrate, 8.713% rosmarinic acid, 4.376% clorogenic acid, and 3.972% salicylic acid. The obtained results from cytotoxicity testing revealed that C. macropodum exerted a significant cytotoxic effect on human neuroblastoma cells at all tested concentrations (p < 0.05). But it did not lead to any cytotoxic potential on human fibroblasts. As a result, the obtained data clearly revealed C. macropodum exerted a selective cytotoxic action on neuroblastoma cells for the first time.
Inhibition of Growth of U87mg Human Glioblastoma Cells by Usnea Longissima Ach
(Acad Brasileira de Ciencias, 2019) Emsen, Bugrahan; Ozdemir, Ozlem; Engin, Tubanur; Togar, Basak; Cavusoglu, Seyda; Turkez, Hasan
Herbal medicines are efficient to reduce side effects in the fight against glioblastoma, which plays a critical role within brain cancer species. The recent studies designated for testing the effects of lichens that have shown numerous anticancer activities on glioblastoma so far. In the present study, different concentrations of water extract obtained from Usnea longissima Ach. were used in order to determine cytotoxic (via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase tests), antioxidant (via total antioxidant capacity test), pro-oxidant (via total oxidant status test) and genotoxic (via 8-hydroxy-2'-deoxyguanosine test) effects of them on human U87MG-glioblastoma cancer cell lines. Primary mixed glial-neuronal non-cancerous cells from Sprague-Dawley rats were also utilized to measure the effects of treatments on non-cancerous cells. Based on median inhibitory concentration values, the data belonged to non-cancerous cells (2486.71 mg/L) showed distinct towering compared to U87MG (80.93 mg/L) cells. The viability of non-cancerous and U87MG cells exposed to extract is decreased in a dose dependent manner. It was also showed that low concentrations of extract notably increased total antioxidant capacity on non-cancerous cells. In addition, various phenolic compounds in extract were detected through high-perfonnance liquid chromatography. The recent results encourage that extract will be able to have therapeutic potential against glioblastoma.
Mitigating Roles by Ulexite Against Acetyleferrocene-Induced Hematotoxicity, Hepatotoxicity, Genotoxicity and Oxidative Stress in Oncorhynchus Mykiss
(Taylor & Francis Ltd, 2024) Ucar, Arzu; Parlak, Veysel; Caglar, Ozge; Yeltekin, Asli Cilingir; Ozgeris, Fatma Betul; Turkez, Hasan; Atamanalp, Muhammed
Acetyl ferrocene (AFC) is being used commonly in several industrial applications and scientific diciplines. Hence, in this study we aimed to determine the LC50 value of AFC, and evaluate the toxicity potential by AFC exposure on rainbow trout (Oncorhynchus mykiss) for 96 h. We also focused to investigate whether UX conferred a protection against AFC-induced toxic insults in fish. For this purpose, some stress related endpoints were measured in blood and liver tissues in a multibiomarker approach. The exposure to AFC observed inhibition/induction of hematological parameters by AFC was slowed down after co-application with UX and AFC. However, UX was found to be ineffective for minimising AFC-induced micronucleus formation after 96 h. Moreover, it was determined that supplementation with UX exhibited activity in favour of antioxidants and inhibited MDA / MPO levels. Again, time-dependent inhibition of Nrf-2 levels, stimulation of IL-6 and TNF-alpha levels by AFC were ameliorated after co-application with UX. Ultimately, administration with UX suppressed the accumulation of 8-OHdG adducts and caspase-3 levels as compared to only AFC treatment. In a conclusion UX exerted significant protection potency against AFC-induced hematotoxic, oxidative, genotoxic and cytotoxic damages, hence could be a new source of natural protective agents in environment.
Modulatory Role Ulexit Against Thiamethoxam-Induced Hematotoxicity/ Hepatotoxicity Oxidative Stress and Immunotoxicity in Oncorhynchus Mykiss
(Elsevier Sci Ltd, 2024) Ucar, Arzu; Gunay, Ayse; Parlak, Veysel; Yeltekin, Asli Cilingir; Ozgeris, Fatma Betul; Turkez, Hasan; Atamanalp, Muhammed
Contamination of the aquatic environment with different insecticides is a major concern in the aquatic ecosystem today. For this reason, in the designed study, Thiamethoxam (TMX) for which there is limited information on its negative effects on Oncorhynchus mykiss was investigated, its effects on hematotoxicity, oxidative status, cytotoxicity, DNA damage and apoptotic status indicators in blood/liver tissue. However, the antitoxic potential of ulexite (UX) supplementation in the elimination of TMX-mediated toxicity has been determined. LC50-96h value determined for TMX 0.73 mg/L has been determined. As a result of hematology profile, TMX application, RBC, Hgb and Hct values showed a temporal decrease compared to the control group, while increases were determined in MCV, MCH and MCHC values. It was determined that the inhibition/induction of hematological parameters was slowed down by adding UX to the medium. During the trial (48th and 96th hours), it was noted that TMX induced cortisol level, while UX supplementation slowed this induction at 48th hour. Antioxidant enzyme activities were significantly inhibited by TMX application, and MDA and MPO values increased as a result of the stimulation of ROS. It was determined that UX added to the medium showed activity in favor of antioxidants and tried to inhibit MDA and MPO levels. When Nrf-2, one of the inflammation parameters, was compared with the administration and control groups, it was determined that it inhibited depending on time, TNF-alpha, IL-6, DNA damage and apoptosis were induced, and UX suppressed this situation. The results obtained were evaluated as statistically meaningful. Briefly, it was determined that TMX induced oxidative damage in all tissues at 48th -96th hours, whereas UX mitigated this situation. The results provide possible in vivo evidence that UX supplements can reduce TMX-mediated oxidative stress and tissues damage in O. mykiss blood and liver tissues.
Neuroprotective Effects of Dietary Borax in the Brain Tissue of Rainbow Trout (Oncorhynchus Mykiss) Exposed To Copper-Induced Toxicity
(Springer, 2018) Alak, Gonca; Ucar, Arzu; Yeltekin, Asli Cilingir; Comakli, Selim; Parlak, Veysel; Tas, Ismail Hakki; Turkez, Hasan
We aimed to investigate the modulating effects of dietary borax on the pathways in rainbow trout brain exposed to copper. For this aim, a comprehensive assessment was performed including biochemical (acetylcholinesterase (AChE), malondialdehyde (MDA), oxidative DNA damage (8-hydroxy-2-deoxyguanosine (8-OHdG), and caspase-3 levels) and transcriptional parameters (heat shock protein 70 (HSP70) and cytochromes P450 (CYP1A), glutathione peroxidase (gpx), superoxide dismutase (sod), and catalase (cat)) parameters and immunohistochemically staining of 8-OHdG. Special fish feed diets were prepared for the trial. These diets contained different concentrations of borax (1.25, 2.5, and 5mg/kg) and/or copper (500 and 1000mg/kg) at the period of pre- and co-treatment strategies for 21days. At the end of the treatment periods, brain tissue was sampled for each experimental group. As a result, the biochemical parameters were increased and AChE activity decreased in the copper and copper-combined groups in comparison with the control group and also with only borax applications (p<0.05). We observed an increase or decrease in particular biochemical parameters for the borax group in every application and we established that borax had protective effect against copper toxicity by decreasing and/or increasing the relevant biochemical parameters in brain tissue of fish. The biochemical results of borax and its combinations corresponded to the observations of gene expression data, which similarly concluded that HSP70 and CYP1A genes were strongly induced by copper (p<0.05). In addition, the expression levels of the sod, cat, and gpx genes in the fish brains exposed to borax and the borax combination groups were significantly higher than the only copper-treated groups. In conclusion, borax supplementation provided significant protection against copper-induced neurotoxicity in trout.
Neuroprotective Properties of Borax Against Aluminum Hydroxide-Induced Neurotoxicity: Possible Role of Nrf-2/Bdnf Pathways in Fish Brain
(Elsevier, 2023) Alak, Gonca; Turkez, Hasan; Ucar, Arzu; Yeltekin, Asli Cilingir; Ozgeris, Fatma Betul; Parlak, Veysel; Atamanalp, Muhammed
The current study was designed to assess the possible neuroprotective effect of borax (BX) against the toxicity of aluminum hydroxide [AH, Al (OH)3] on brain of rainbow trout (Oncorhynchus mykiss) with multibiomarker approaches. For this purpose, the presence of the neuroprotective action by BX against the AH exposure was assessed by the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), myeloperoxidase (MPO), acetylcholinesterase (AChE). In addition, we evaluated glutathione (GSH), malondialdehyde (MDA), DNA damage (8-OHdG), apoptosis (caspase 3), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), nuclear factor erythroid-2 (Nrf-2), and brain-derived neurotrophic factor (BDNF) levels in 96 h semi-static treatment. In the 48th and 96th hour samplings, apoptosis induced by AH in the Nrf-2/BDNF/AChE pathways in rainbow trout brain tissue was revealed by DNA damage, enzyme inhibitions and lipid peroxidations. On the contrary applications of BX supported antioxidant capacity without leading apoptosis, lipid peroxidation, inflammatory response and DNA damage. BX also increased the BDNF levels and AChE activity. Moreover, BX exerted a neuroprotective effect against AH-induced neurotoxicity via down-regulating cytokine-related pathways, minimising DNA damage, apoptosis as well as up-regulating GSH, AChE, BDNF and antioxidant enzyme levels. It can be concluded that the combination of borax with AH modulated the toxic effects of AH.
Oxidative and Dna Damage Potential of Colemanite on Zebrafish: Brain, Liver and Blood
(Central Fisheries Research inst, 2020) Alak, Gonca; Parlak, Veysel; Ucar, Arzu; Yeltekin, Asli Cilingir; Ozgeris, Fatma Betul; Caglar, Ozge; Turkez, Hasan
Recently, boron has been used in animal feeding due to its significant biological roles. In this study, the action mechanism of colemanite (COL), a commercially important borate mineral, was aimed to investigate via evaluating parameters related to oxidative alterations on the brain, liver and blood tissues of zebrafish. For this purpose, zebrafish were exposed to different doses of COL (5, 10 and 20 mg/L) in a static test apparatus for 96 hours. Multiple biochemical analysis including determination of DNA damage (8-OHdG), apoptosis (Caspase-3), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), myeloperoxidase (MPO), paraoxonase (PON), arylesterase (AR) and lipid peroxidation (MDA) levels were performed in brain and liver tissues for assessing oxidative responses. In addition to micronucleus (MN) assay was performed in obtained blood tissues. The results indicated that low doses of COL supported antioxidant system and did not lead to oxidative stress in zebrafish brain and liver. Again, our results showed colemanite did not cause DNA damage or apoptosis at all tested concentrations. Besides the statistically insignificant changes (P>0.05) of MN rates of erythrocytes between the control and experimental groups revealed the non-genotoxic feature of COL on zebrafish. In conclusion, boron compounds especially COL can be used safely and provide positive impacts on aquatic environments.
The Protective Effect Exerted by Dietary Borax on Toxicity Metabolism in Rainbow Trout (Oncorhynchus Mykiss) Tissues
(Elsevier Science inc, 2019) Alak, Gonca; Parlak, Veysel; Yeltekin, Asli Cilingir; Ucar, Arzu; Comakli, Selim; Topal, Ahmet; Turkez, Hasan
The aim of this study was to evaluate the effectiveness of borax (BX) against heavy metal exposure on the transcriptional and biochemical reaction in vivo and alleviating effect on gill and liver tissues of rainbow trout. Due to this aim, fish were fed with different level of BX and/or copper (Cu) (1.25, 2.5 and 5 mg/kg of BX; 500 and 1000 mg/kg of Cu) for 21.days in pre- and co-treatment options. The transcriptional parameters [(heat-shock protein 70 (hsp70), and cytochromes P450 (cyp1a), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT))], antioxidant enzyme activities (SOD, CAT and GPx), malondialdehyde (MDA), oxidative DNA damage (8-hydroxy-2'-deoxyguanosine (8-OHdG) and caspase-3 levels were investigated in different tissues samples of treated and control fish. Our results revealed that antioxidant enzyme activity was increased and levels of 8-OHdG, Caspase-3 and MDA were decreased in the BX and BX combined groups as compared to the copper combination group and to copper-only application during pre- and co-treatment (p < 0.05). Similarly, hsp70 and cyp1a gene expressions were decreased after treatment with BX. As conclusion, we suggest that borax itself is not an antioxidant it supportes antioxidant defense mechanism of fish disrupted by heavy metals.
Synthesis and Biological Evaluation of Novel Benzylidene Thiazolo Pyrimidin-3(5h) Derivatives
(Taylor & Francis Ltd, 2024) Akbas, Esvet; Othman, Khdir A.; Celikezen, Fatih Caglar; Ejder, Nebahat Aydogan; Turkez, Hasan; Yapca, Omer Erkan; Mardinoglu, Adil
Starting compound 1 was synthesized according to reference.(1) Benzylidene thiazole pyrimidin-3(5H)-ones were synthesized reactions of 1 with bromoacetic acid and various aryl-aldehydes in the same vessel via one-step, unlike studies in the literature. Quantum chemical parameters and full geometry optimizations for all compounds were computed using DFT based on B3LYP. Cytotoxic action potential of synthesized compounds was evaluated using trypan blue dye exclusion and MTT assays in different cell lines including adenocarcinoma alveolar basal epithelial-like adherent A549 cells, the colon adenocarcinoma HT-29 cells, prostate adenocarcinoma DU-145 cells, and diploid ARPE-19 retinal pigment epithelial cells. Embryotoxicity and genotoxicity assessments were performed on pluripotent human embryonal carcinoma NT2 and human lymphocyte cells, respectively. Compound A1 exhibited good anticancer activity on A549 and DU-145 cell lines, and the compounds including A3, 4, 6, and 9 induced cytotoxicity on A549 cells. The compounds A1-10 also showed a good biosafety profile at relatively lower concentrations.
Synthesis of the 3,5-Diphenyl and Cytogenetic and Oxidative Alterations After Exposure of Cultured Human Whole Blood Cells
(Taylor & Francis As, 2017) Akbas, Esvet; Celikezen, Fatih Caglar; Turkez, Hasan; Ozdemir, Ozlem; Ruzgar, Adem; Ergan, Erdem; Sahin, Ertan
The 3,5-diphenyl-1H-pyrazole was obtained by condensation reaction of dibenzoylmethane and thiosemicarbazide in acetic acid under conventional heating and microwave irradiation method. The structure of the 3,5-diphenyl-1H-pyrazole confirmed by IR, H-1, and C-13 NMR and X-ray diffraction and the geometry optimization was carried out using density functional theory (DFT) methods at B3LYP/6-31G, 6-31G(d), 6-31G(d, p), 6-311G(d, p), 6-311G(2d, 2p), 6-31+G(d, p), 6-311++G(d, p) levels. In addition, cytotoxic and oxidative effects were investigated in cultured human peripheral blood cells.
Synthesis, Characterization, Theoretical Studies and in Vitro Embriyotoxic, Genotoxic and Anticancer Effects of Novel Phenyl(1,4,6-Triphenyl
(Taylor & Francis Ltd, 2024) Akbas, Esvet; Othman, Khdir A.; Celikezen, Fatih Caglar; Ejder, Nebahat Aydogan; Turkez, Hasan; Yapca, Omer Erkan; Mardinoglu, Adil
In this study, phenyl (1,4,6-triphenyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)methanone was obtained by using the Biginelli reaction method. The structure of this compound was analyzed using elemental analysis, IR, 1H, and 13C NMR. The quantum chemical calculations (QCC) of this compound were performed density functional theory (DFT) method, 6-31 G (d, p) base set, and B3LYP functions with the Gaussian09W software package. Literature shows that pyrimidine-derived compounds have very active biological properties. For this reason, the biologically active properties of the synthesized compound were also examined. To determine embryotoxic, genotoxic, and cytotoxic effects of compound, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), lactate dehydrogenase (LDH) release, micronucleus (MN) and 8-OH-dG assays were carried out. On the other hand, pharmacokinetic and toxicity properties (ADMET) were predicted in silico via SwissADME and Protox-II web tools. In silico estimates of this compound used in the study showed that the compound has the covetable physicochemical properties for bioavailability. In conclusion, the obtained results of our study clearly showed that this compound exerted strong toxicity potential.
Ulexite Modulates the Neurotoxicological Outcomes of Acetylferrocene-Exposed Rainbow Trout
(Wiley, 2022) Ucar, Arzu; Ozgeris, Fatma Betul; Parlak, Veysel; Yeltekin, Asli Cilingir; Turkez, Hasan; Alak, Gonca; Atamanalp, Muhammed
In this study, the neuroprotective action potential by ulexite (UX) (18.75 mg/L) against acetylferrocene (AFC) (3.82 mg/L) induced neurotoxicity was aimed to investigate in brain tissues of Oncorhynchus mykiss. For this purpose, the effects on neurotoxicity markers, proinflammatory cytokines, antioxidant immune system, DNA, and apoptosis mechanisms were assessed on brain tissues in the 48-96 h of the 96- trial period. In this research, it was determined that brain-derived nerve cell growth factor (BDNF) level and acetylcholinesterase (AChE) activity were inhibited in the brain tissue compared to the control group by AFC. In addition, inhibition in glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) values (which are antioxidant system biomarkers), and inductions in malondialdehyde (MDA) and myeloperoxidase (MPO) amounts (which are indicators of lipid peroxidation) were determined (p < 0.05) after exposure to AFC. And, while tumor necrosis factor-alpha (TNF-alpha) and IL-6 levels were increased in the AFC-exposed group, Nrf-2 levels were found to be remarkably decreased. Upregulation was also detected in 8-hydroxydeoxyguanosine (8-OHdG) and caspase-3 levels, which are related to DNA damage and apoptosis mechanism. On the contrary, UX (single/with AFC) suppressed the AChE and BDNF inhibition by AFC. Moreover, UX mitigated AFC-induced oxidative, inflammatory, and DNA damage and attenuated AFC-mediated neurotoxicity via activating Nrf2 signaling in fish. Collectively, our findings revealed that UX supplementation might exert beneficial effects and may be considered as a natural and promising neuroprotective agent against AFC-induced toxicity.