Browsing by Author "Geyikoglu, Fatime"

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The Ameliorative Effect of Cetraria Islandica Against Diabetes-Induced Genetic and Oxidative Damage in Human Blood
(Taylor & Francis Ltd, 2013) Colak, Suat; Geyikoglu, Fatime; Turkez, Hasan; Bakir, Tulay Ozhan; Aslan, Ali
Context: The aqueous extracts of Cetraria islandica (L.) Ach. (Parmeliaceae) is traditionally used in many countries against a number of conditions, including inflammatory conditions. Objective: The present study aimed to assess, for the first time, the effectiveness of C. islandica in cultured primary blood cells of Type 1 diabetes subjects. Materials and methods: Diabetic and control blood samples were treated with or without aqueous lichen extract (5 and 10 mu g mL(-1)) for 48 h. The activity of antioxidant enzymes in erythrocytes and also malondialdehyde levels in plasma were determined to evaluate the oxidative status. DNA damages were analyzed by SCE, MN and comet assays in cultured human lymphocytes. Additionally, proliferation index (PI) was evaluated in peripheral blood lymphocytes. Results: There were significant increases in observed total DNA damage (comet assay) (240.2%) and SCE (168.8%), but not in MN frequencies of cultures with diabetes as compared (p>0.05) to controls. Whereas, the significant reductions of total DNA damage (69.2 and 65.3%) and SCE frequencies (17.7 and 12.3%) were determined when the 5 and 10 mg mL(-1) lichen extract was added to the cell culture medium, respectively. However, lichen extract did not completely inhibit the induction of SCEs in lymphocytes of patients with diabetes. C. islandica extract was also useful on PI rates. Discussion: In conclusion, the antioxidant role of C. islandica in alleviating diabetes-induced genomic instability and for increasing cell viability was firstly indicated in the present study.
Ameliorative Effect of Supplementation with L-Glutamine on Oxidative Stress, DNA Damage, Cell Viability and Hepatotoxicity Induced by 2,3,7,8-Tetrachlorodibenzo in Rat Hepatocyte Cultures
(Springer, 2012) Turkez, Hasan; Geyikoglu, Fatime; Yousef, Mokhtar I.; Celik, Kubra; Bakir, Tulay O.
The most potent of the dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is a persistent and ubiquitous environmental contaminant. And the health impact of exposure to TCDD is of great concern to the general public. Recent data indicate that l-glutamine (Gln) has antioxidant properties and may influence hepatotoxicity. The objective of the present study was undertaken to explore the effectiveness of Gln in alleviating the hepatotoxicity of TCDD on primary cultured rat hepatocytes. Gln (0.5, 1 and 2 mM) was added to cultures alone or simultaneously with TCDD (0.005 and 0.01 mM). The hepatocytes were treated with TCDD and Gln 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), total glutathione (TGSH) and total oxidative stress (TOS) levels were determined to evaluate the oxidative injury. The DNA damage was also analyzed by liver micronucleus assay (MN) and 8-oxo-2-deoxyguanosine (8-OH-dG). The results of MTT and LDH assays showed that TCDD decreased cell viability but not l-glutamine. TCDD also increased TOS level in rat hepatocytes and significantly decreased TAC and TGSH levels. On the basis of increasing doses, the dioxin in a dose-dependent manner caused significant increases of micronucleated hepatocytes (MNHEPs) and 8-OH-dG as compared to control culture. Whereas, in cultures exposured with Gln alone, TOS levels were not changed and TAC and TGSH together were significantly increased in dose-dependent fashion. The presence of Gln with TCDD modulated the hepatotoxic effects of TCDD on primary hepatocytes cultures. Noteworthy, Gln has a protective effect against TCDD-mediated DNA damages. As conclusion, we reported here an increased potential therapeutic significance of l-glutamine in TCDD-mediated hepatic injury for the first time.
Ameliorative Effects of Docosahexaenoic Acid on the Toxicity Induced by 2,3,7,8-Tetrachlorodibenzo in Cultured Rat Hepatocytes
(Sage Publications Inc, 2016) Turkez, Hasan; Geyikoglu, Fatime; Yousef, Mokhtar I.
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 M) in the presence and absence of DHA (5, 10, and 20 M) for 48 h. The cell viability was detected by 3-(4,5-dimethylthiazol-2-yl) 2,5diphenyltetrazolium 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.
Antioxidative, Anticancer and Genotoxic Properties of Α-Pinene on N2a Neuroblastoma Cells
(Springer, 2013) Aydin, Elanur; Turkez, Hasan; Geyikoglu, Fatime
alpha-Pinene, an organic monoterpene, is found in essential oils of pine and coniferous trees. To date, although various biological activities of alpha-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 alpha-pinene. Statistical analysis of MTT assay results indicated significant (p < 0.05) decreases of the cell proliferation rates in healthy neurons treated with alpha-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 alpha-pinene treatment caused increases of TAC levels in primary rat neurons without any alterations of its level in N2a cells. However, alpha-pinene treatments at higher doses led to increases of TOS levels in both cell types. Overall our results suggest that alpha-pinene is of a limited therapeutic use as an anticancer agent.
Antiproliferative, Genotoxic and Oxidant Activities of Cyclosativene in Rat Neuron and Neuroblastoma Cell Lines
(Inst Bioloska Istrazivanja Sinisa Stankovic, 2014) Togar, Basak; Turkez, Hasan; Geyikoglu, Fatime; Hacimuftuoglu, Ahmet; Tatar, Abdulgani
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 mu 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.
Beneficial Effect of Astaxanthin on 2,3,7,8-Tetrachlorodibenzo Liver Injury in Rats
(Sage Publications Inc, 2013) Turkez, Hasan; Geyikoglu, Fatime; Yousef, Mokhtar I.
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) represents a potential health risk and hepatotoxicity. Astaxanthin (ASTA) exhibits antioxidant properties and can influence hepatotoxicity. Therefore, the present study was carried out for using ASTA against hepatotoxicity induced by TCDD in the liver of rats. Animals were treated intraperitoneally daily with TCDD (8 mu g/kg body weight (b.w.)), ASTA (12.5 mg/kg b.w. and 25 mg/kg b.w.) and TCDD plus ASTA (12.5 and 25 mg/kg b.w.) for 21 days. TCDD significantly decreased the activities of antioxidant enzymes and resulted in serious pathological findings. Moreover, the rate of micronucleus (MN) in hepatocytes increased after treating with TCDD. The activities of enzymes, frequencies of MNs and liver histology in lower dosage group of ASTA remained unchanged compared with the control group. In rats treated with ASTA, at higher dosage alone, the MNs remained unchanged and the activities of antioxidant enzymes significantly increased. The presence of ASTA (except for lower dose) with TCDD alleviated its pathological effects in hepatic tissue. ASTA also prevented the suppression of antioxidant enzymes in the livers of animals exposed to TCDD and displayed a strong protective effect against MNs. Thus, the present findings might provide new insight into the development of therapeutic and preventive approaches of TCDD toxicity.
The Biochemical and Histological Effects of Lichens in Normal and Diabetic Rats
(Sage Publications Inc, 2016) Deniz, Gulsah Yildiz; Geyikoglu, Fatime; Turkez, Hasan; Bakir, Tulay Ozhan; Colak, Suat; Aslan, Ali
Oxidative stress plays an important role in causing diabetes; however, no studies have thoroughly reported on the toxic and beneficial effects of lichen extracts in patients with diabetes mellitus (DM). This study covers a previously unrecognized effect of two well-known lichen species Cetraria islandica and Pseudevernia furfuracae in streptozotocin (STZ)-induced diabetes. In experimental design, control or diabetic rats were either untreated or treated with aqueous lichen extracts (250-500 mg/kg /day) for 2 weeks starting at 72 h after STZ injection. On day 14, animals were anaesthetized, and metabolic and biochemical parameters were appreciated between control and treatment groups. The histopathology of liver was examined using three different staining methods: hematoxylin-eosin (H&E), periodic acid Schiff (PAS), and reticulin and Sudan Black B. Our experimental data showed that increasing doses of C. islandica and P. furfuracae alone did not have any detrimental effects on studied parameters and the malondialdehyde level of liver. C. islandica extract showed positive results for antioxidant capacity compared to doses of P. furfuracae extract. However, the protective effect of C. islandica extract on diabetes-induced disorders and hepatic damages is still unclear. Moreover, unfortunately, animals subjected to DM therapy did not benefit from the usage of increasing lichen doses due to their unchanged antioxidant activity in tissues. The results obtained in present study suggested that C. islandica and P. furfuracae is safe but the power of these is limited because of intensive oxidative stress in liver of type 1 diabetic rats. It is also implied that C. islandica extract is especially suitable for different administration routes in DM animals.
Borax Counteracts Genotoxicity of Aluminum in Rat Liver
(Sage Publications Inc, 2013) Turkez, Hasan; Geyikoglu, Fatime; Tatar, Abdulgani
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; 5mg/kg b.w.) and BX (3.25 and 13mg/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.
The Carvacrol Ameliorates Acute Pancreatitis-Induced Liver Injury Via Antioxidant Response
(Springer, 2016) Bakir, Murat; Geyikoglu, Fatime; Colak, Suat; Turkez, Hasan; Bakir, Tulay Ozhan; Hosseinigouzdagani, Mirkhalil
Acute pancreatitis (AP) may cause significant persistent multi-organ dysfunction. Carvacrol (CAR) possesses a variety of biological and pharmacological properties. The aim of the present study was to analyze the hepatic protection of CAR on AP induced by cerulein and to explore the underlying mechanism using in vivo studies. The rats were randomized into groups to receive (1) no therapy; (2) 50 A mu g/kg cerulein at 1-h intervals by four intraperitoneal injection (i.p.); (3) 50, 100 and 200 mg/kg CAR by one i.p.; and (4) cerulein + CAR after 2 h of cerulein injection. 12 h later, serum was provided to assess the blood AST, ALT and LDH values. Also, liver tissues were obtained for histological and biochemical measurements. Liver oxidative stress markers were evaluated by changes in the amount of lipid peroxides measured as MDA and changes in tissue antioxidant enzyme levels, SOD, CAT and GSH-Px. Histopathological examination was performed using scoring systems. Oxidative damage to DNA was quantitated in studied tissues of experimental animals by measuring the increase in 8-hydroxydeoxyguanosine (8-OHdG) formations. We found that the increasing doses of CAR decreased pancreatitis-induced MDA and 8-OH-dG levels. Moreover, the liver SOD, CAT and GSH-Px activities in the AP + CAR group were higher than that of the rats in the AP group. In the treatment groups, AST, ALT and LDH were reduced. Besides, necrosis, coagulation and inflammation in the liver were alleviated (p < 0.05). We suggest that CAR could be a safe and potent new drug candidate for treating AP through its antioxidative mechanism of action for the treatment of a wide range of disorders related to hepatic dysfunction.
Carvacrol Modulates Oxidative Stress and Decreases Cell Injury in Pancreas of Rats with Acute Pancreatitis
(Springer, 2016) Kilic, Yeliz; Geyikoglu, Fatime; Colak, Suat; Turkez, Hasan; Bakir, Murat; Hsseinigouzdagani, Mirkhalil
Acute pancreatitis (AP) is considered as major problem around the world and the incidence of AP is increasing. Carvacrol (CAR), a monoterpenic phenol, has good antioxidant activity. This in vivo study was designed to evaluate whether CAR provide protection against AP that developed by pancreas injury. The rats were randomised into groups to receive (I) no therapy; (II) 50 A mu g/kg cerulein at 1 h intervals by four intraperitonally (i.p.) injections; (III) 50, 100 and 200 mg/kg CAR by one i.p. injection; and (IV) cerulein plus CAR after 2 h of cerulein administration. 12 h later, serum samples were obtained to assess pancreatic function, the lipase and amylase values. The oxidative stress markers were evaluated by changes in the amount of lipid peroxides measured as malondialdehyde (MDA) and changes in main tissue antioxidant enzyme levels including SOD, CAT and GSH-PX. Histopathological examination was performed using scoring systems. Additionally, oxidative DNA damage was determined by measuring the increases of 8-hydroxy-deoxyguanosine (8-OH-dG) formations. We found that the increasing doses of CAR decreased AP-induced MDA and 8-OH-dG levels. Moreover, the pancreas antioxidant enzyme activities were higher than that of the rats in the AP group when compared to the AP plus CAR group. In the treatment groups, the lipase and amylase were reduced. Besides, histopathological findings in the pancreatic tissue were alleviated (p < 0.05). We suggest that CAR could be a safe and potent new drug candidate for treating AP through its antioxidative mechanism of action for the treatment of a wide range of disorders related to pancreas.
Cytotoxic and Cytogenetic Effects of α-Copaene on Rat Neuron and N2a Neuroblastoma Cell Lines
(Springer, 2014) Turkez, Hasan; Togar, Basak; Tatar, Abdulgani; Geyikoglu, Fatime; Hacimuftuoglu, Ahmet
Alpha-copaene (alpha-COP), a tricyclic sesquiterpene, is present in several essential oils of medicinal and aromatic plants and has antioxidant and antigenotoxic features. Its cytotoxic, cytogenetic and oxidative effects have not been investigated in neuron and N2a neuroblastoma (NB) cell cultures. Therefore, we aimed to describe in vitro: (i) cytotoxic properties by 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenlytetrazolium bromide test; (ii) antioxidant/oxidant activity by total antioxidant capacity (TAC) and total oxidative status (TOS) analysis; and (iii) genotoxic damage potential by single cell gel electrophoresis - of alpha-COP in healthy neuron and N2a-NB cell cultures for the first time. Significant (P < 0.05) decrease in cell proliferation were observed in cultured primary rat neurons starting with the concentration of 150 mg/L and in N2a-NB cells starting with 100 mg/L. In addition, 25 mg/L of alpha-COP treatment caused increase of TAC levels and alpha-COP treatments at higher doses led to increase of TOS levels in neuron N2a-NB cell cultures. Moreover, none of the tested concentrations of alpha-COP have shown a genotoxic effect on both cell lines. Our findings clearly demonstrate that alpha-COP exhibited mild cytotoxic effects on N2a-NB cell line. In conclusion, alpha-COP may have potential as an anticancer agent, which needs to be further studied.
Cytotoxicity and Genotoxicity of Zingiberene on Different Neuron Cell Lines in Vitro
(Springer, 2015) Togar, Basak; Turkez, Hasan; Tatar, Abdulgani; Hacimuftuoglu, Ahmet; Geyikoglu, Fatime
The main objective of this study is to investigate the cytotoxic, genotoxic and antioxidant properties of zingiberene (ZBN) in an in vitro rat brain cell culture study. The cytotoxic effect was determined against the rat neuron and N2a neuroblastoma (N2a-NB) cell lines using the 3,(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, while the antioxidant activity was assessed using the total antioxidant capacity (TAC) and total oxidative stress (TOS) assays. The effects on DNA damage were also evaluated in this study by the single cell gel electrophoresis assay. The results indicated that ZBN has an anti-proliferative activity suppressing the proliferation of N2a-NB cells at concentrations over 50 mg L-1 and neuron cells at concentrations over 150 mg L-1. In addition, ZBN treatments at higher doses (10-400 mg L-1) led to increases of TOS levels in N2a-NB cell cultures. However 25 mg L-1 of ZBN treatment caused increases of TAC levels in cultured neuron and N2a-NB cell cultures while ZBN at doses of 10-400 mg L-1 did not increase the number of total damage score in both cell lines. This study clearly indicates that ZBN has a significant potential to be used as a natural anticancer agent in cultured N2a-NBs.
The Effect of Laurel Leaf Extract Against Toxicity Induced by 2,3,7,8-Tetrachlorodibenzo in Cultured Rat Hepatocytes
(Inst Medical Research & Occupational Health, 2011) Turkez, Hasan; Geyikoglu, Fatime
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a very toxic environmental pollutant that raises great public concern about its impact on human health. Recent studies indicate that laurel leaf extract exhibits antioxidant properties that can counter the toxic effects of certain compounds in the liver. The aim of this study was to assess how effective LE is against the toxicity of TCDD in a primary culture of rat hepatocytes. The extract (50 mg L-1, 100 mg L-1, and 200 mg L-1) was added to cultures alone or with TCDD (1.61 mg L-1 and 3.22 mg L-1) for 48 hours. Cell viability was measured using the [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide] (MTT) assay and the lactate dehydrogenase (LDH) cytotoxicity assay, while oxidative damage was assessed by measuring total antioxidant capacity (TAC) and total oxidative stress (TOS). DNA damage was also analysed using the micronucleus (MN) assay of the cultured hepatocytes. TCDD alone lowered, and laurel extract had no effect on cell viability. TCDD also increased TOS and significantly decreased TAG. It significantly increased the frequency of micronucleated hepatocytes in a dose-dependent manner. In cultures exposed to LE alone, TOS did not change and TAG significantly increased in a dose-dependent manner. Added to TCDD, laurel countered its toxic effects and showed protective effects against TCDD-mediated DNA damage. This points to the therapeutic potential of laurel against TCDD toxicity in the liver.
Effect of Oleuropein Against Chemotherapy Drug-Induced Histological Changes, Oxidative Stress, and DNA Damages in Rat Kidney Injury
(Food & Drug Administration, 2017) Geyikoglu, Fatime; Emir, Murat; Colak, Suat; Koc, Kubra; Turkez, Hasan; Bakir, Murat; Ozek, Nihal Simsek
Cisplatin-based chemotherapy is responsible for a large number of renal failures, and it is still associated with high rates of mortality today. Oleuropein (OLE) presents a plethora of pharmacological beneficial properties. In this study we investigated whether OLE could provide sufficient protection against cisplatin-induced nephrotoxicity. With this aim, Sprague-Dawley rats were divided into eight groups: control; 7 mg/kg/d cisplatin, 50 mg/kg, 100 mg/kg, and 200 mg/kg OLE; and treatment with OLE for 3 days starting at 24 hours following cisplatin injection. After exposure to the chemotherapy agent and OLE, oxidative DNA damage was quantitated in the renal tissue of experimental animals by measuring the amount of 8-hydroxy-20-deoxyguanosine (8-OHdG) adducts. Malondialdehyde (MDA) level, total oxidative stress (TOS), and total antioxidant status (TAS) were assessed to determine the oxidative injury in kidney cells. The histology of the kidney was examined using four different staining methods: hematoxylin-eosin (H& E), periodic acid Schiff (PAS), Masson trichrome, and amyloid. In addition, the blood urea nitrogen (BUN), uric acid (UA), and creatinine (CRE) levels were established. Our experimental data showed that tissue 8OHdG levels were significantly higher in the cisplatin group when compared to the control group. The glomerular cells were sensitive to cisplatin as tubular cells. In addition, treatment with cisplatin elevated the levels of BUN, UA, CRE, and TOS, but lowered the level of TAS compared to the control group. The OLE therapy modulated oxidative stress in order to restore normal kidney function and reduced the formation of 8-OHdG induced by cisplatin. Furthermore, the OLE treatment significantly reduced pathological findings in renal tissue. We demonstrate for the first time that OLE presents significant cytoprotective properties against cisplatin-induced genotoxicity by restoring the antioxidant system of the renal tissue. According to our findings, OLE is a promising novel natural source for the prevention of serious kidney damage in current chemotherapies. Copyright (C) 2016, Food and Drug Administration, Taiwan. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license.
The Effects of Cetraria Islandica and Pseudevernia Furfuracea Extracts in Normal and Diabetic Rats
(Sage Publications Inc, 2015) Bakir, Tulay Ozhan; Geyikoglu, Fatime; Colak, Suat; Turkez, Hasan; Aslan, Ali; Bakir, Murat
Lichens are symbiotic organisms composed of a fungus joined to a photosynthesizing partner that can be either an alga or a cyanobacterium. They can be used as a novel bioresource for natural antioxidants. However, there is also a need for further studies to validate the lichens used in medicinal remedies. This study covers a previously unrecognized effects of Cetraria islandica (CIAE) and Pseudeverniafurfuracea (PFAE) in streptozotocin (STZ)-induced diabetes. In experimental design, control or diabetic rats were either untreated or treated with aqueous lichen extracts (250-500 mg/kg/day) for 2 weeks starting at 72 h after STZ injection. On day 14, animals were anesthetized, metabolic and biochemical parameters were appreciated between control and treatment groups. The histopathology of kidney was examined using four different staining methods: hematoxylin-eosin (H&E), periodic acid-Schiff (PAS), Masson trichrome and Congo red. Our experimental data showed that increasing doses of CIAE and PFAE did not have any detrimental effects on the studied parameters and the malondialdehyde level of kidney. CIAE extract showed prominent results compared to doses of PFAE extract for antioxidant capacity. However, the protective effect of CIAE extract was inadequate on diabetes-induced disorders and kidney damages. Moreover, animals subjected to diabetes mellitus (DM) therapy did not benefit unfortunately from the usage of increasing lichen doses due to their unchanged antioxidant activity to tissue. The results obtained in present study suggested that CIAE and PFAE are safe but the power of these is limited because of the intensive oxidative stress in kidney of type 1 diabetic rats. It is also implied that CIAE extract is especially suitable for different administration routes in DM.
The Efficacy of Carvacrol on Renal Damage in Rats with Acute Pancreatitis
(Taylor & Francis Ltd, 2014) Hsseinigouzdagani, Mirkhalil; Geyikoglu, Fatime; Colak, Suat; Turkez, Hasan; Bakir, Tuelay Ozhan; Bakir, Murat
The carvacrol is thought to promote optimal health via its antioxidant and free radical scavenging effects. The aim of our present study was to investigate the efficacy of carvacrol on the development of kidney injury in acute pancreatitis model (AP) induced by cerulein and to explore the underlying mechanism. The rats were randomised into groups to receive (I) no therapy; (II.) 50 mu g/kg cerulein at 1-h intervals by four intraperitonally injection (i.p.); (III) 50, 100 and 200 mg/kg carvacrol by one i.p.; and (IV) cerulein+carvacrol after 2 h of cerulein injection. 12 h later, serum was provided to assess the blood urea nitrogen (BUN), creatinine (CRE) and uric acid (UA) values. Also, renal tissues were obtained for histological and biochemical measurements. Kidney oxidative stress markers were evaluated by changes in the amount of lipid peroxides measured as malondialdehyde (MDA) and changes in tissue antioxidant enzyme levels, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-PX). Histopathological examination was performed using scoring systems. We found that the increasing doses of carvacrol decreased pancreatitis-induced MDA levels. Moreover, the renal SOD, CAT and GSH-Px activities in the AP+carvacrol group were higher than that of the rats in the AP group. In the treatment groups, the BUN, CRE and UA were reduced. Besides, necrosis, coagulation and inflammation in the kidney were alleviated (p < 0.05). Finally, the magnitude of the protective effect on kidney is certain, and 200 mg/kg carvacrol is an effective theraphy for oxidative stress caused by AP.
Evaluating the Toxic and Beneficial Effects of Lichen Extracts in Normal and Diabetic Rats
(Sage Publications Inc, 2016) Colak, Suat; Geyikoglu, Fatime; Bakir, Tulay Ozhan; Turkez, Hasan; Aslan, Ali
Lichens can be used as a novel bioresource for natural antioxidants. However, there is need for further investigations to validate the lichens used in medicinal remedies. In this study, the effects of Cetraria islandica and Pseudevernia furfuracae lichen species in streptozotocin (STZ)-induced diabetes were evaluated. Diabetic rats were treated with aqueous lichen extracts (250 and 500 mg/kg/day) for 2 weeks starting at 72 h after STZ injection. On the 14th day, animals were anesthetized, and then metabolic and biochemical parameters were evaluated between control and treatment groups. Pancreatic histology and -cell mass were examined by hematoxylin and eosin and insulin immunohistochemistry stainings. Our findings revealed that these lichen species could be used safely in this dose range. In addition, C. islandica extracts showed prominent results compared to the doses of P. furfuracae extract for antioxidant capacity. However, the protectivity of C. islandica extract was inadequate against diabetes-induced pancreatic damages via forming oxidative stress. In conclusion, the usage of C. islandica might serve for early intervening in the risk reduction of type 1 diabetes.
Genotoxic and Oxidative Damage Potentials in Human Lymphocytes After Exposure to Terpinolene in Vitro
(Springer, 2015) Turkez, Hasan; Aydin, Elanur; Geyikoglu, Fatime; Cetin, Damla
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.
The Genotoxic, Hepatotoxic, Nephrotoxic, Haematotoxic and Histopathological Effects in Rats After Aluminium Chronic Intoxication
(Sage Publications Inc, 2013) Geyikoglu, Fatime; Turkez, Hasan; Bakir, Tulay Ozhan; Cicek, Mustafa
Aluminium (Al) is used in water purification and is also present in several manufactured foods and medicines. Al is known to induce a broad range of physiological, biochemical and behavioural dysfunctions in laboratory animals and humans. This investigation was carried out to investigate the effects of subchronic exposure to Al (as AlCl3) in rats. Sprague-Dawley rats were randomly separated into two groups. Group 1 rats treated with sodium chloride served as the control, group 2 rats were treated with Al (as AlCl3, 5mg/kg body weight) intraperitonally for 10 weeks. Animals were killed and blood samples were analyzed for blood serum alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) enzyme activities and creatinine, urea (U) and uric acid (UA) levels for evaluating hepatotoxicity and nephrotoxicity. Blood parameters including red blood cells (RBCs), haemoglobin (Hb) concentration, haematocrit (Ht), platelets (PLTs) and white blood cells (WBCs) were compared between control and experimental group to assess haematoxicity. In order to determine the genotoxicity, the number of micronucleated hepatocytes (MNHEPs) was counted in isolated hepatocytes. In addition, histological alterations in liver and kidney samples were investigated. After exposure with Al, the enzymatic activities of ALP, AST, ALT and LDH, and the levels of U and UA significantly increased. RBC, WBC, PLT, Hb and Ht revealed significant decreases in experimental group compared to the control. AlCl3 caused a significant increase in MNHEPs. Furthermore, severe pathological damages were established in both liver and kidney samples. Subchronic exposure to low doses of Al can produce serious dysfunctions in rat blood, liver and kidney, and exposure to this metal can result in greater damages.
Guaiazulene Biochemical Activity and Cytotoxic and Genotoxic Eff Ects on Rat Neuron and N2a Neuroblastom Cells
(Ejmanager LLC, 2015) Togar, Basak; Turkez, Hasan; Hacimuftuoglu, Ahmet; Tatar, Abdulgani; Geyikoglu, Fatime
Aim: Neuroblastoma (NB) cells are often used in cancer researches such as glioblastoma cells since they have the potential of high mitotic activity, nuclear pleomorphism, and tumor necrosis. Guaiazulene (GYZ 1,4-dimethyl-7-isopropylazulene) is present in several essential oils of medicinal and aromatic plants. Many studies have reported the cytotoxic effect of GYZ; however, there are no studies that compare such effects between cancer cell lines and normal human cells after treatment with GYZ. Materials and Methods: In this study, we aimed to describe in vitro antiproliferative and/or cytotoxic properties (by 3-[4,5 dimetylthiazol -2-yl]-2,5 diphenlytetrazolium bromide [MTT] test), oxidative effects (by total antioxidant capacity [TAC] and total oxidative stress [TOS] analysis) and genotoxic damage potentials (by single cell gel electrophoresis) of GYZ. Result: The results indicated that GYZ have anti-proliferative activity suppressing the proliferation of neuron and N2a-NB cells at high doses. In addition, GYZ treatments at higher doses led to decreases of TAC levels and increases of TOS levels in neuron and N2a-NB cells. On the other hand, the mean values of the total scores of cells showing DNA damage were not found different from the control values. Conclusion: From this study, it is observed that GYZ has in vitro cytotoxic activity against neuron and N2a-NB cells.