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Epilepsy is a neurological disorder resulting from abnormal neuronal firing in the brain. Glutamate transporters and the glutamate-glutamine cycle play crucial roles in the development of seizures. In the present study, the correlation of epilepsy with glutamate transporters and enzymes was investigated. Herein, male Wistar rats were randomly allocated into four groups (six animals/group); 35 mg/kg pentylenetetrazole (PTZ) was used to induce a kindling model of epilepsy. Once the kindling model was established, animals were treated for 15 days with either valproic acid (VPA, 350 mg/kg) or ceftriaxone (CEF, 200 mg/kg) in addition to the control group receiving saline. After treatment, electrocorticography (ECoG) was performed to record the electrical activity of the cerebral cortex. The glutamate reuptake time (T80 ) was also determined in situ using an in vivo voltammetry. The expression levels of glutamate transporters and enzymes in the M1 and CA3 areas of the brain were determined using a real-time polymerase chain reaction (RT-PCR). ECoG measurements showed that the mean spike number of the PTZ + VPA and PTZ + CEF groups was significantly lower (p < 0.05) than that of the PTZ group. Compared with the PTZ group, VPA or CEF treatment decreased the glutamate reuptake time (T80 ). The expression levels of EAAC1, GLT-1, GLAST, glutamine synthetase (GS), and glutaminase were increased in the PTZ group. Treatment with VPA or CEF enhanced the expression levels of GLT-1, GLAST, EAAC1, and GS, whereas the glutaminase expression level was reduced. The current results suggest that VPA or CEF decreases seizure activity by increasing glutamate reuptake by upregulating GLT-1 and GLAST expression, implying a possible mechanism for treating epilepsy. Also, we have suggested a novel mechanism for the antiepileptic activity of VPA via decreasing glutaminase expression levels. To our knowledge, this is the first study to measure the glutamate reuptake time in situ during the seizure (i.e., real-time measurement).
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PentilenotetrazolRESUMEN
BACKGROUND AND OBJECTIVE: Metformin (MET) has been used as an antidiabetic agent for type II diabetes. At the same time, recent researches have shown that the clinical improvement of MET is useful for nerve damage. In this study, we investigated the analgesic effect of MET in paclitaxel (PAC)-induced neuropathic pain. MATERIALS AND METHODS: Forty-two adult, female rats, Wistar strain weighing 220 ± 10 g were randomly divided into 5 experimental groups. PAC was intraperitoneally (IP) administered (2.0 mg/kg) for 4 groups every other day (0, 2, 4, and 6 days). By the 30th day, MET (100, 200, and 400 mg/kg) was administered to 4 groups. Before and after treatment, basal pain threshold values were measured with Randall-Selitto analgesiometer test. At the end of experiment, pathological values were measured in selected regions including brain (motor cortex, M1), spinal cord (L4-L5), sciatic nerve, and muscle. RESULTS: According to our results, PAC-induced neuropathic pain reached to highest level at 14th day. Four hundred milligram/kilogram concentration of MET remarkably decreased PAC-induced neuropathic pain. On the other hand, pathologic features have shown that PAC had significant pathological change in the brain and spinal cord while in the peripheral nerves and muscles had not shown any pathological change. CONCLUSION: The pathological results of the current study for the first time demonstrated that MET beside of its antidiabetic effects reversed neuropathic pain induced by PAC. Consequently, this research can be promising for cancer patients that suffering from neuropathic pain induced by anticancer drugs.
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Analgésicos/farmacología , Hipoglucemiantes/farmacología , Metformina/farmacología , Neoplasias/complicaciones , Neuralgia/prevención & control , Paclitaxel/efectos adversos , Umbral del Dolor/efectos de los fármacos , Animales , Antineoplásicos Fitogénicos/efectos adversos , Modelos Animales de Enfermedad , Femenino , Neoplasias/patología , Neuralgia/inducido químicamente , Neuralgia/patología , Ratas , Ratas WistarRESUMEN
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-performance liquid chromatography. The recent results encourage that extract will be able to have therapeutic potential against glioblastoma.
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Antioxidantes/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Extractos Vegetales/farmacología , Usnea/química , Animales , Antioxidantes/uso terapéutico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Humanos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Ratas , Ratas Sprague-DawleyRESUMEN
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.
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Dibenzoxepinas/farmacología , Linfocitos/citología , Estrés Oxidativo/efectos de los fármacos , Parmeliaceae/química , Salicilatos/farmacología , 8-Hidroxi-2'-Desoxicoguanosina , Adulto , Células Cultivadas , Desoxiguanosina/análogos & derivados , Desoxiguanosina/análisis , Dibenzoxepinas/química , Relación Dosis-Respuesta a Droga , Humanos , Linfocitos/efectos de los fármacos , Estructura Molecular , Salicilatos/química , Metabolismo Secundario , Adulto JovenRESUMEN
This paper describes the development of mitoxantrone-loaded PEGylated graphene oxide/magnetite nanoparticles (PEG-GO/Fe3O4-MTX), and investigation of its preliminary drug delivery performance. For this, the GO was synthesized through oxidizing graphite powder, and subsequently carboxylated using a substitution nucleophilic reaction. The carboxylated GO (GO-COOH) was then conjugated with amine end-caped PEG chains by Steglich esterification. Afterward, GO-PEG/Fe3O4 nanocomposite was synthesized through the anchoring of Fe3O4 nanoparticles onto the surface of GO-PEG during the sonication. The biocompatibility and MTX-loading capacity of the synthesized GO-PEG/Fe3O4 nanocomposite were evaluated. The pH dependent drug release behavior and cytotoxicity effect of the MTX-loaded GO-PEG/Fe3O4 nanocomposite were also studied. According to biocompatibility, pH dependent drug release behavior as well as superior physicochemical and biological characteristics of graphene and magnetite nanoparticles, it is expected that the GO-PEG/Fe3O4 nanocomposite may be applied as de novo drug delivery system (DDS) for cancer therapy using both chemo- and photothermal therapy approaches.
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Antineoplásicos/administración & dosificación , Preparaciones de Acción Retardada/química , Grafito/química , Nanopartículas de Magnetita/química , Mitoxantrona/administración & dosificación , Nanocompuestos/química , Polietilenglicoles/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Humanos , Concentración de Iones de Hidrógeno , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Mitoxantrona/farmacocinética , Mitoxantrona/farmacología , Neoplasias/tratamiento farmacológico , Óxidos/químicaRESUMEN
Boron compounds have an ability of supporting antioxidant properties in human and animal tissues. Lithium metaborate dihydrate (LiBO2·2H2O; LMD) is commonly used in nonlinear optic materials, cellular phones and pagers. But, there are limited data on the genotoxic and antioxidant effects of LMD in cultured human whole blood cells. The aim of this study was to evaluate for the genotoxicity and antioxidant/oxidant activity of LMD on human whole blood lymphocytes (n = 5). LMD was applied at various concentrations (0-1,280 µg/ml) to cultured blood samples. Antioxidant/oxidant activity was evaluated by measuring the total oxidant status (TOS) and total antioxidant capacity levels. Micronuclei and chromosomal aberration tests were used in genotoxicity studies. Our results clearly revealed that all tested concentrations of LMD were found to be non-genotoxic when compared to that of the control group. In addition, LMD exhibited antioxidant activities at low concentrations. In addition the TOS levels were not changed at all concentrations of LMD. Consequently, our results clearly demonstrated that LMD is non-genotoxic and it has an important antioxidant potential in vitro.
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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.
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Antineoplásicos Fitogénicos/farmacología , Benzoxepinas/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Ácidos Carboxílicos/farmacología , Corteza Cerebral/efectos de los fármacos , Dibenzoxepinas/farmacología , Glioblastoma/tratamiento farmacológico , Líquenes , Neuronas/efectos de los fármacos , Extractos Vegetales/farmacología , Salicilatos/farmacología , 8-Hidroxi-2'-Desoxicoguanosina , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/toxicidad , Benzoxepinas/aislamiento & purificación , Benzoxepinas/toxicidad , Biomarcadores/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Ácidos Carboxílicos/aislamiento & purificación , Ácidos Carboxílicos/toxicidad , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Corteza Cerebral/metabolismo , Daño del ADN , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Dibenzoxepinas/aislamiento & purificación , Dibenzoxepinas/toxicidad , Relación Dosis-Respuesta a Droga , Glioblastoma/metabolismo , Glioblastoma/patología , Humanos , L-Lactato Deshidrogenasa/metabolismo , Líquenes/química , Neuronas/metabolismo , Neuronas/patología , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidad , Ratas Sprague-Dawley , Salicilatos/aislamiento & purificación , Salicilatos/toxicidad , Factores de TiempoRESUMEN
Paclitaxel (PAC) and cisplatin (CIS) are two established chemotherapeutic drugs used in combination for the treatment of various solid tumors. However, the usage of PAC and CIS are limited because of the incidence of their moderate or severe neurotoxic side effects. In this study, we aimed to assess the protective role of salicylic acid (SA) against neurotoxicity caused by PAC and CIS. For this purpose, newborn Sprague Dawley rats were decapitated in sterile atmosphere and primary cortex neuron cultures were established. On the 10th day SA was added into culture plates. PAC and CIS were added on the 12th day. The cytotoxicity was determined by using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Oxidative alterations were assessed using total antioxidant capacity and total oxidative stress assays in rat primary neuron cell cultures. It was shown that both concentrations of PAC and CIS treatments caused neurotoxicity. Although SA decreased the neurotoxicity by CIS and PAC, it was more effective against the toxicity caused by CIS rather than the toxicity caused by PAC. In conclusion it was clearly revealed that SA decreased the neurotoxic effect of CIS and PAC in vitro.
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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.
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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 (≤50 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.
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Sesquiterpenes have attracted much interest with respect to their protective effect against oxidative damage that may be the cause of many diseases including several neurodegenerative disorders and cancer. Our previous unpublished work suggested that cyclosativene (CSV), a tetracyclic sesquiterpene, has antioxidant and anticarcinogenic features. However, little is known about the effects of CSV 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 CSV in H2O2-induced toxicity in new-born rat cerebral cortex cell cultures for the first time. For this aim, MTT and lactate dehydrogenase release assays were carried out to evaluate cytotoxicity. Total antioxidant capacity (TAC) and total oxidative stress (TOS) parameters were used to evaluate oxidative changes. In addition to determining of 8-hydroxy-2-deoxyguanosine (8-OH-dG) levels, the single cell gel electrophoresis (or 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 H2O2 alone treated cultures. But pre-treatment of CSV suppressed the cytotoxicity, genotoxicity and oxidative stress which were increased by H2O2. On the basis of these observations, it is suggested that CSV as a natural product with an antioxidant capacity in mitigating oxidative injuries in the field of neurodegenerative disorders.
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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.
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Daño del ADN , Durapatita/toxicidad , Linfocitos/efectos de los fármacos , Micronúcleos con Defecto Cromosómico/inducido químicamente , Nanopartículas , Intercambio de Cromátides Hermanas/efectos de los fármacos , 8-Hidroxi-2'-Desoxicoguanosina , Antioxidantes/metabolismo , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Relación Dosis-Respuesta a Droga , Durapatita/química , Humanos , Linfocitos/metabolismo , Linfocitos/patología , Masculino , Pruebas de Mutagenicidad , Estrés Oxidativo/efectos de los fármacos , Cultivo Primario de CélulasRESUMEN
One of the useful and most commonly cultivated commercially species, migratory locust (Locusta migratoria; Orthoptera), was investigated in light of genotoxic damage potentials. For this aim, we evaluated the genotoxic potentials of water soluble extracts of L. migratoria on cultured human blood cells. The micronucleus, sister chromatid exchange and structural chromosome aberration assays were applied to assess DNA and chromosomal damage produced by aqueous extracts in vitro. The extracts were added to the cultures at different concentrations ranging from 0 to 1000 mg/L. Our results indicated that these extracts did not exhibit genotoxicity at tested concentrations. We conclude that this in vitro approach for biomonitoring genotoxicity assessment is useful for comparing the potential health risks of edible insects.
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Productos Biológicos/toxicidad , Aberraciones Cromosómicas/inducido químicamente , Daño del ADN/efectos de los fármacos , Locusta migratoria/genética , Mutágenos/toxicidad , Animales , Humanos , Linfocitos/efectos de los fármacos , Masculino , Pruebas de Mutagenicidad , Intercambio de Cromátides Hermanas/efectos de los fármacosRESUMEN
Potassium tetraborate (PTB) is a product resulting from the controlled reaction of potassium hydroxide, water and boric acid (BA). It is used in many areas of industry such as disinfectant, detergent and treatment of contact lenses. PTB is one of the boron compounds which is most commonly used in many areas of industry although very limited information is available concerning its toxicity. Therefore, in this study, it is aimed to determine genetic and biochemical effects of PTB in human blood cell cultures (n=4). PTB was added into culture tubes at various concentrations (0-1280 µg/ml). Micronucleus (MN) and chromosomal aberration (CA) tests were performed for genotoxic damage influences estimation. In addition, biochemical parameters (total antioxidant capacity (TAC) and total oxidative status (TOS) were examined to determine oxidative effects. The results indicated that all tested concentrations of PTB were found to be non-genotoxic. In addition, low concentrations (1.25, 2.5 and 5 µg/ml) of PTB caused increases of TAC levels. Furthermore, all concentrations of PTB were not changed the TOS levels in cultured human blood cells. Based on these results, in this study it has been reported for the first time that PTB is not genotoxic and it increases the antioxidant capacity in human peripheral blood lymphocytes.
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In this study, the cytotoxic, genotoxic/antigenotoxic and antioxidant/oxidant activity of copaene (COP), a plant-derived tricyclic sesquiterpene, on human lymphocyte cultures (n = 5) was investigated. COP was added into culture tubes at various concentrations (0, 10, 25, 50, 100, 200 and 400 mg/L). While the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays were used for viability and cytotoxic evaluations, the micronucleus (MN) and sister chromatid exchange (SCE) assays were used for genetic evaluations. Moreover, total antioxidant capacity (TAC) and total oxidative status analysis were used for biochemical evaluations. According to LDH and MTT assays COP significantly reduced cell proliferation at high concentrations (200 and 400 mg/L). In addition, there was no significant increase (P < 0.05) in both SCE and MN frequencies of cultures treated with COP as compared to controls. We have also concluded that concentrations of COP of 50 and 100 mg/L increased TAC level when compared to the controls. In conclusion, in this study it has been reported for the first time that copaene is not genotoxic and it increases the antioxidant capacity in human lymphocyte cultures.
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The purpose of this study was to evaluate the effect of carotenoid astaxanthin (ASTA) on cultured primary rat hepatocytes treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the cell viability (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, MTT), lactate dehydrogenase (LDH) activity, 8-oxo-2-deoxyguanosine (8-OH-dG), total antioxidant capacity (TAC), and total oxidative stress (TOS) levels, and liver micronucleus rates. ASTA (2.5, 5, and 10 µM) was added to cultures alone or simultaneously with TCDD (5 and 10 µM) for 48 h. The results of MTT and LDH assays showed that both doses of TCDD caused significant decrease in cell viability. Also, TCDD significantly increased TOS and decreased TAC level in rat hepatocytes. On the basis of increasing doses, the dioxin caused significant increase in micronucleated hepatocytes) and 8-OH-dG level as compared to control culture. The presence of ASTA with TCDD minimized its effects on primary hepatocytes cultures and DNA damages.
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Hepatocitos/efectos de los fármacos , Dibenzodioxinas Policloradas/toxicidad , 8-Hidroxi-2'-Desoxicoguanosina , Animales , Antioxidantes/farmacología , Supervivencia Celular , Células Cultivadas , Daño del ADN/efectos de los fármacos , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Relación Dosis-Respuesta a Droga , Hepatocitos/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Hígado/citología , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Pruebas de Micronúcleos , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Sales de Tetrazolio/metabolismo , Tiazoles/metabolismo , Xantófilas/farmacologíaRESUMEN
OBJECTIVE: The present investigation was undertaken to assess the protective effect of Laurus nobilis leaf extract (LNE) against aluminum phosphide (AIP)-induced genotoxic and oxidative damages stress in cultured human blood cells in the presence of a metabolic activator (S9 mix). MATERIALS AND METHODS: Sister chromatid exchange (SCE) and chromosome aberration (CA) assays were used to assess AlP-induced genotoxicity and to establish the protective effects of LNE. In addition, we determined total antioxidant capacity (TAC) and total oxidative status (TOS) levels in AlP and LNE treated cultures for biomonitoring the oxidative alterations. RESULTS: There was significant increases (P < 0.05) in both SCE and CA frequencies of cultures treated with AlP as compared to controls. Our results also showed that AlP (58 mg/l) caused oxidative stress by altering TAC and TOS levels. However, co-application of LNE (25, 50, 100 and 200 mg/l) and AlP resulted in decreases of SCE, CA rates and TOS level and increases of TAC level as compared to the group treated with AlP alone. CONCLUSION: The preventive role of LNE in alleviating AlP-induced DNA and oxidative damages was indicated for the first time in the present study.
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Compuestos de Aluminio/toxicidad , Daño del ADN/efectos de los fármacos , Laurus/química , Estrés Oxidativo/efectos de los fármacos , Plaguicidas/toxicidad , Fosfinas/toxicidad , Extractos Vegetales/farmacología , Hojas de la Planta/química , Células Cultivadas/efectos de los fármacos , Aberraciones Cromosómicas/efectos de los fármacos , Femenino , Humanos , Oxidación-Reducción , Intercambio de Cromátides Hermanas/efectos de los fármacosRESUMEN
Aluminum phosphide (AlP) is a colorless, flammable, liquefied pesticide that is commonly used to control insects, nematodes, weeds, and pathogens in crops, forests, ornamental nurseries, and wood products. Early investigations of AlP-poisoned mammalian cells led to the proposed involvement of oxidative damage in its toxicity mechanism. Therefore, this study was aimed to evaluate the effect of Laurus nobilis (L) leaf extract (LNE) against AlP-induced genetic and oxidative damages in rats. Selected animals were assigned to four groups (n = 6), namely, group A: control (only distilled water is injected); group B: AlP (4 mg kg(-1) injected intraperitoneally (i.p.)); group C: LNE (200 mg kg(-1) injected i.p.), and group D: AlP plus LNE, respectively. The experimental period lasted for 14 successive days. Chromosomal aberrations (CAs) and micronucleus (MN) assay were used for monitoring genotoxic damage. In addition, biochemical parameters such as total antioxidant capacity (TAC) and total oxidative status (TOS) were examined in serum samples to determine oxidative damage. Our results indicated that AlP caused increase in CA and MN assay rates and alterations in TAC and TOS levels when compared with control group. On the contrary, LNE did not change the rates of both the analyzed cytogenetic end points and led to increase in TAC level. Moreover, we observed that LNE suppressed the genetic damage by AlP to bone marrow cells in vivo. Interestingly AlP-induced oxidative stress was also strongly reduced by LNE. The results of the present study indicated that the protective effect of LNE might be ascribable to its antioxidant and free radical scavenging properties.
Asunto(s)
Compuestos de Aluminio/toxicidad , Aberraciones Cromosómicas/inducido químicamente , Laurus/química , Estrés Oxidativo/efectos de los fármacos , Fosfinas/toxicidad , Extractos Vegetales/farmacología , Análisis de Varianza , Animales , Antioxidantes/farmacología , Peso Corporal , Masculino , Pruebas de Micronúcleos , Mutágenos/toxicidad , Hojas de la Planta/química , Ratas , Ratas Sprague-DawleyRESUMEN
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces hepatic damage. Propolis exhibits antioxidant properties and several studies suggest that supplementations with antioxidants can influence hepatotoxicity. Therefore, the aim of the current study was to explore the effectiveness of propolis in alleviating the toxicity of TCDD in the liver of rats. Animals were divided into six groups, namely, TCDD (0.75 and 8 µg/kg body weight (bw)), propolis (50 mg/kg bw), TCDD (0.75 and 8 µg) plus propolis (50 mg/kg bw), and control, respectively. Rats were intraperitoneally administered with their respective doses daily for 21 days. In rats that received a high dose of TCDD, the antioxidant enzymes were significantly decreased and the serious pathological findings were established. Also, the rate of hepatocyte micronucleus (HMN) was increased after treating with TCDD. The reactions of enzymes in control and low-dose group were weak. The frequencies of HMN and liver histology were similar to both the groups. The presence of propolis with TCDD alleviated its pathological effects in hepatic tissue. Propolis also prevented the suppression of antioxidant enzymes in the livers of animals exposed to TCDD and displayed a strong protective effect against HMN. It can be concluded that propolis has beneficial influences and was able to antagonize TCDD toxicity in the liver.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Daño del ADN/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Dibenzodioxinas Policloradas/toxicidad , Própolis/farmacología , Animales , Antioxidantes/farmacología , Relación Dosis-Respuesta a Droga , Hepatocitos/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
In this study, the cytogenetic and oxidative effects of water soluble extracts of two commonly eaten insects, Zonocerus variegatus (Orthoptera: Pyrgomorphidae) and Oryctes boas (Solanales: Solanaceae), in southwestern Nigeria were evaluated on cultured human blood cells. The extracts were added to the cultures at various concentrations (0-2000 ppm). The chromosome aberration and micronucleus tests were used to find out the DNA and chromosomal damage potentials in vitro by aqueous insect extracts. To assess the oxidative effects of these insect extracts, total antioxidant capacity (TAC) and total oxidant status (TOS) levels were also measured. Our results indicated that these extracts did not show genotoxic effects at the tested concentrations. However, the extracts caused dose-dependent alterations in both TAC and TOS levels. Based on the findings, it was concluded that the studied insects can be consumed safely, but it is necessary to consider the cellular damages that are likely to appear depending on the oxidative stress. We also suggest that this in vitro approach for oxidative and genotoxicity assessments may be useful to compare the potential health risks of edible insects.