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Pesticides are globally used to eliminate pests from crops and plants. The increased use of pesticides has posed a serious threat to human health. This study evaluates the effects of pesticide exposure on pregnancy outcomes in tea garden workers (TGW). The acetylcholinesterase (AChE) activity was measured in the maternal blood, placenta, and cord blood of TGW and housewives (HWs). The placental structure and expression of hypoxia-inducible factor (HIF)-1α were also analyzed in TGW and HW groups delivering low birth weight (LBW) and normal birth weight (NBW) babies. A significantly decreased AChE activity was observed in maternal blood and cord blood in TGW as compared with HW in the LBW group. However, it did not change significantly in the NBW group (p < .05). The adjusted regression analysis of birth outcomes (birth weight, head circumference, infant's length, and ponderal index) revealed a significant and positive association with the levels of AChE activity in maternal blood, placenta, and cord blood in TGW (p < .05). The histological analysis showed significantly higher placental syncytial knots, chorangiosis, fibrinoid deposition, necrosis, and stromal fibrosis in the LBW group of TGW. Microinfarction, increased fibrinoid deposition, and atypical villi characteristics, such as mushroom-like structures, were observed during scanning electron microscopy along with increased HIF-1α expression in placental tissues of TGW exposed to pesticides. Results suggest that occupational pesticide exposure during pregnancy may decrease AChE activity and cause in utero pathological changes accompanied by an increased HIF-1α expression, which also contributes to placental insufficiency and fetal growth restriction.
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Acetilcolinesterasa/sangre , Exposición Materna/efectos adversos , Exposición Profesional/efectos adversos , Plaguicidas/toxicidad , Placenta/metabolismo , Té , Adulto , Femenino , Proteínas Ligadas a GPI/sangre , Humanos , Masculino , Placenta/patología , EmbarazoRESUMEN
AIM: This study was aimed to evaluate the association of maternal determinants with birth weight (BW) of babies in tea garden workers (TGW) and housewives (HW). METHODS: A total of 175 subjects were recruited from Assam Medical College, Dibrugarh, India. In this cross-sectional study, maternal determinants, BW of babies and placental weight were explored in TGW (n = 102) and HW (n = 73). These factors were assessed and correlated by logistic regression models. RESULTS: A higher incidence of low birth weight (LBW) was found in mothers working in the tea garden (48.04%) as compared to HW (10.96%). Activity of plucking of leaves in tea garden by women had a higher risk for LBW babies (adjusted odd ratio [AOR] 4.33, 95% confidence interval [CI] 1.38-13.57, P = 0.012) and decreased placental weight (AOR 11.42, 95% CI 1.18-126.02, P = 0.036) as compared to HW considered as reference group. Women who worked continuously in the tea garden during 9 months of pregnancy also revealed an elevated risk for LBW (AOR 5.32, 95% CI 1.34-21.09, P = 0.017). CONCLUSION: This study suggests the activity of plucking of tea leaves by women is associated with LBW of babies and decreased placental weight. Particularly, if mothers worked continuously in the tea garden during 9 months of pregnancy, it also increased the risk of delivering LBW babies. This exploratory study provides an important platform for further prospective studies, which could be focused on the potential consequences of maternal occupational exposures during pregnancy on fetal development.
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Recién Nacido de Bajo Peso , Adolescente , Adulto , Estudios de Casos y Controles , Estudios Transversales , Agricultores/estadística & datos numéricos , Femenino , Humanos , India/epidemiología , Placenta/patología , Embarazo , Factores de Riesgo , Población Rural , Té , Adulto JovenRESUMEN
Bisphenol A (BPA), a well-known xenoestrogen, is ubiquitously utilized in manufacturing of polycarbonated plastics. Convincing evidence suggests that BPA induces neurotoxicity and certain behavioral deficits. α-Lipoic acid (ALA) supplementation has shown protective effect against heart and liver diseases, diabetes, and neurological debility associated with aging. We studied the neuromodulatory effect of ALA against neurotoxicity of BPA in vitro in C8-D1A mouse astrocyte cell line and in vivo in C57BL/6J male mice. In vitro ALA (100⯵M) protected cells from BPA (30⯵M)-induced reactive oxygen species generation and increased activity of glial fibrillary acidic protein. ALA showed reduction in cell death in astrocytes treated with BPA. In vivo ALA (50â¯mg/kg) increased the neurospecific acetylcholinesterase activity and decreased the monoamine oxidase activity altered by BPA exposure (10â¯mg/kg, per os x 30 days). In addition to neuroprotective effects, ALA also showed protective effects against BPA-induced oxidative stress. We observed that ALA significantly replenished the declined neurobehavioral and cognitive performances, decreased muscle coordination and alerted short-term recognition memory in mice exposed to BPA. Our results suggest that ALA has a promising role in modulating BPA-induced neurotoxicity in C8-D1A mouse astrocyte cells as well as neurochemical and neurobehavioral deficits in C57BL/6J male mice and its antioxidant and free radical scavenging activities may in part be responsible for such an effect.
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Antioxidantes/farmacología , Compuestos de Bencidrilo/toxicidad , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Fenoles/toxicidad , Reconocimiento en Psicología/efectos de los fármacos , Ácido Tióctico/farmacología , Animales , Células Cultivadas , Masculino , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo/fisiología , Reconocimiento en Psicología/fisiologíaRESUMEN
INTRODUCTION: Bisphenol A (BPA) is suspected to cause hormonal imbalance in humans. Dietary factors are known to bring changes in hormonal profile. In order to study chemico-biological interaction of iron deficiency on toxicity outcome of BPA exposure, we studied the modulatory effects of iron deficiency on the hormone levels in rats chronically-exposed to BPA. METHODS: Weanling rats maintained on normal and iron-deficient diets were exposed to low level of BPA at 0, 1, 5 and 10 ppm for six months through drinking water. The serum levels of thyroidstimulating hormone (TSH), testosterone, progesterone and estradiol were measured in the animals by enzyme-linked immunosorbent assay kit. Histopathology was performed to check the pathological changes in gonads. RESULTS: No significant change was observed in TSH, progesterone and estradiol levels at 1 and 5 ppm BPA. However, at 10 ppm BPA a significant increase in TSH level was observed in the animals maintained on an iron-deficient diet of either sex. BPA caused a significant change in testosterone level even at 5 and 10 ppm doses in animals of either sex. However, in male rats 1 ppm dose also showed a significant effect in the animals maintained on iron deficient diet. Changes in the histoarchitecture of the testes at high dose of BPA (10 ppm) were more remarkable in anemic rats. CONCLUSION: These results suggest that iron deficiency has no generalized effect on hormonal levels in BPA-treated animals and trends indicate a more remarkable effect in male animals at hormonal and tissue levels.
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Anemia Ferropénica/sangre , Compuestos de Bencidrilo/toxicidad , Disruptores Endocrinos/toxicidad , Hormonas/sangre , Fenoles/toxicidad , Testículo/efectos de los fármacos , Anemia Ferropénica/diagnóstico , Anemia Ferropénica/patología , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Estradiol/sangre , Femenino , Masculino , Ovario/efectos de los fármacos , Ovario/metabolismo , Ovario/patología , Progesterona/sangre , Ratas Wistar , Factores Sexuales , Testículo/metabolismo , Testículo/patología , Testosterona/sangre , Tirotropina/sangre , Factores de Tiempo , DesteteRESUMEN
Oxidative stress-related inflammation and apoptosis are important pathogenic consequences, which result in acute pulmonary toxicity. Bleomycin (BLM) is used to treat various forms of cancers. However, its prolonged administration is associated with major toxicity to respiratory system. We studied the effect of walnut (Juglans regia) extract in a rat model of BLM-induced pulmonary toxicopathy. We also studied parameters of inflammation, apoptosis and oxidative stress in various groups of animals. Prophylactic treatment of total methanolic extract of walnut at the dose of 150mg/kg b.w. was given per os to Wistar rats for 14days prior to BLM exposure. A single intratracheal injection of BLM (10U/kg b.w.) was administered on the eleventh day of the treatment. There was a marked increase in the hydroxyproline level, lipid peroxidation, nitric oxide production, and in the activities of xanthine oxidase and myeloperoxidase in the lung tissue in BLM-treated animals when compared to control animals. BLM also decreased the activities of antioxidant enzymes such as glutathione reductase and catalase and increased the lung inflammation and apoptosis by upregulating the NF-κB signaling pathway and caspase-3 expression. Treatment with walnut extract attenuated these changes in a significant manner. Walnut extract significantly modulated the lung injury as measured by markers of cellular injury such as lactate dehydrogenase and alkaline phosphatase, total cell count, total protein and reduced glutathione in bronchoalveolar lavage fluid. Histological findings supported the protective effects of walnut extract against BLM-induced lung injury. Walnut which has been shown to have numerous medicinally valuable constituents including ellagic acid showed efficacy in preventing the various toxicopathological effects of BLM in rat lungs. Overall, walnut extract decreases BLM-induced oxidative stress and lung inflammation by modulating the alveolar macrophage inflammatory response in rats and thus protecting them from the pathological effect of BLM.
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Juglans/química , Pulmón/patología , Extractos Vegetales/farmacología , Fosfatasa Alcalina/metabolismo , Animales , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Bleomicina , Líquido del Lavado Bronquioalveolar , Caspasa 3/metabolismo , Ciclooxigenasa 2/metabolismo , Ácido Elágico/farmacología , Inmunohistoquímica , Inflamación/patología , L-Lactato Deshidrogenasa/metabolismo , Masculino , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/farmacología , Ratas WistarRESUMEN
OBJECTIVE: There is an urge to identify new molecules which can modulate process of epileptogenesis, since currently available drugs act symptomatically and one-third of the patients remain refractory to the disease. Hence, the present study was conducted to evaluate the effects of Resveratrol (RESV) on epileptogenesis in pentylenetetrazole (PTZ)-induced kindling in mice. METHOD: Swiss albino mice were administered RESV (10, 20 and 40â mg/kg,p.o) in acute study. On the seventh day animals were subjected to various neurological and neurobehavioral tests viz, Increasing Current Electroshock Test (ICES), PTZ-induced seizures, passive avoidance response, and elevated plus maze test. For the development of kindling PTZ was administered in a dose of 25â mg/kg, i.p. on every alternate day and RESV in all the three doses was administered daily. Seizure score was continuously monitored till the development of kindling and cognition tests were performed in the end of the study. The animals were sacrificed and levels of inflammatory biomarkers viz., IL-1ß, interleukin-1 receptor antagonist (IL1-Ra), IL-6, and TNF-α were assessed in the hippocampus and cortex of the kindled animals. RESULTS: RESV in all three doses increased the seizure threshold to hind limb extension in the ICES test. RESV in all the tested doses suppressed the development of kindling and reduced the levels of IL-1ß, IL1-Ra, IL-6, and TNF-α in kindled mice. CONCLUSION: RESV suppressed the development of kindling in mice and decreased the levels of inflammatory biomarkers in their hippocampus. RESV modified brain inflammation during epileptogenesis and found to possess nootropic activity in the kindled mice.
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Antiinflamatorios no Esteroideos/uso terapéutico , Anticonvulsivantes/uso terapéutico , Corteza Cerebral/metabolismo , Suplementos Dietéticos , Hipocampo/metabolismo , Convulsiones/prevención & control , Estilbenos/uso terapéutico , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Anticonvulsivantes/administración & dosificación , Antioxidantes/administración & dosificación , Antioxidantes/uso terapéutico , Reacción de Prevención/efectos de los fármacos , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/inmunología , Convulsivantes/antagonistas & inhibidores , Convulsivantes/toxicidad , Encefalitis/inducido químicamente , Encefalitis/inmunología , Encefalitis/metabolismo , Encefalitis/prevención & control , Femenino , Hipocampo/efectos de los fármacos , Hipocampo/inmunología , Mediadores de Inflamación/antagonistas & inhibidores , Mediadores de Inflamación/metabolismo , Excitación Neurológica/efectos de los fármacos , Excitación Neurológica/inmunología , Excitación Neurológica/metabolismo , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , Neuronas/efectos de los fármacos , Neuronas/inmunología , Neuronas/metabolismo , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/uso terapéutico , Pentilenotetrazol/antagonistas & inhibidores , Pentilenotetrazol/toxicidad , Distribución Aleatoria , Resveratrol , Convulsiones/inducido químicamente , Convulsiones/inmunología , Convulsiones/metabolismo , Estilbenos/administración & dosificaciónRESUMEN
Nonylphenol (NP), an environmental endocrine disruptor mimics estrogen and is a potential toxicant both under in vitro and in vivo conditions. In this study, the effect of melatonin on NP- induced neurotoxicity and cognitive alteration was investigated in adult male Wistar rats. Melatonin supplementation has been known to protect cells from neurotoxic injury. The animals were divided into three groups namely, control (vehicle) which received olive oil orally and treated rats received NP (25 mg/kg, per os) thrice a week for 45 days while the third group i.e., NP + melatonin, animals were co-administered melatonin (10 mg/kg, i.p.) along with NP. On the 46th day, rats were assessed for anxiety, motor co-ordination, grip strength and cognitive performance using Morris water maze test and then sacrificed for biochemical and histopathological assays in brain tissues. Melatonin improved the behavioral performance in NP exposed group. The results showed that NP significantly decreased the activity of acetylcholine esterase (AchE), monoamine oxidase (MAO) and Na+/K+-ATPase, in rat brain tissue along with other enzymes of antioxidant milieu. The outcome of the study shows that NP, like other persistent endocrine disrupting pollutants, creates a potential risk of cognitive, neurochemical and histopathological perturbations as a result of environmental exposure. Taken together, our study demonstrates that melatonin is protective against NP-induced neurotoxicity.
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Antioxidantes/farmacología , Lóbulo Frontal/efectos de los fármacos , Hipocampo/efectos de los fármacos , Melatonina/farmacología , Animales , Lóbulo Frontal/metabolismo , Hipocampo/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fenoles/farmacología , Ratas WistarRESUMEN
Bisphenol A (BPA), an estrogenic and endocrine disrupting agent, is widely used in manufacturing of polycarbonate plastics and epoxy resins. BPA and other endocrine disrupting chemicals (EDCs) act via multiple mechanisms including interference with mitochondrial functions. Mitochondria are the hub of cellular energy pool and hence are the target of many EDCs. We studied perturbation of activities of mitochondrial enzymes by BPA and its possible role in hepatotoxicity in Wistar rats. Rats were exposed to BPA (150 mg/kg, 250 mg/kg, 500 mg/kg per os, for 14 days) and activities of enzymes of mitochondrial electron transport chain (ETC) were measured. Besides, other biochemical parameters such as superoxide generation, protein oxidation, and lipid peroxidation (LPO) were also measured. Our results indicated a significant decrease in the activities of enzymes of mitochondrial ETC complexes, i.e., complex I, II, III, IV, and V along with significant increase in LPO and protein oxidation. Additionally, a significant increase in mitochondrial superoxide generation was also observed. All these findings could be attributed to enhanced oxidative stress, decrease in reduced glutathione level, and decrease in the activity of superoxide dismutase in rat liver mitochondria isolated from BPA-treated rats. BPA treatment also caused a significant increase in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase indicating its potential hepatotoxicity. Furthermore, histopathological findings revealed marked edema formation, hepatocellular degeneration, and necrosis of liver tissue in BPA-exposed rats. In conclusion, this study provides an evidence of impaired mitochondrial bioenergetics and liver toxicity after high-dose BPA exposure in rats. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1922-1934, 2016.
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Compuestos de Bencidrilo/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Disruptores Endocrinos/toxicidad , Mitocondrias Hepáticas/efectos de los fármacos , Fenoles/toxicidad , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Complejo I de Transporte de Electrón/metabolismo , Glutatión/metabolismo , Peroxidación de Lípido , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Mitocondrias Hepáticas/metabolismo , Estrés Oxidativo , Ratas Wistar , Superóxido Dismutasa/metabolismoRESUMEN
In environmental risk assessments (ERA), biomarkers have been widely used as an early warning signal of environmental contamination. However, biomarker responses have limitation due to its low relevance to adverse outcomes (e.g., fluctuations in community structure, decreases in population size, and other similar ecobiologically relevant indicators of community structure and function). To mitigate these limitations, the concept of adverse outcome pathways (AOPs) was developed. An AOP is an analytical, sequentially progressive pathway that links a molecular initiating event (MIE) to an adverse outcome. Recently, AOPs have been recognized as a potential informational tool by which the implications of molecular biomarkers in ERA can be better understood. To demonstrate the utility of AOPs in biomarker-based ERA, here we discuss a series of three different biological repercussions caused by exposure to benzo(a)pyrene (BaP), silver nanoparticles (AgNPs), and selenium (Se). Using mainly aquatic invertebrates and selected vertebrates as model species, we focus on the development of the AOP concept. Aquatic organisms are suitable bioindicator species whose entire lifespans can be observed over a short period; moreover, these species can be studied on the molecular and population levels. Also, interspecific differences between aquatic organisms are important to consider in an AOP framework, since these differences are an integral part of the natural environment. The development of an environmental pollutant-mediated AOP may enable a better understanding of the effects of environmental pollutants in different scenarios in the diverse community of an ecosystem.
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Exposición a Riesgos Ambientales , Peces/embriología , Peces/metabolismo , Teratógenos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Organismos Acuáticos/efectos de los fármacos , Benzo(a)pireno/toxicidad , Biomarcadores/metabolismo , Monitoreo del Ambiente , Nanopartículas del Metal/toxicidad , Neoplasias/inducido químicamente , Neoplasias/veterinaria , Medición de Riesgo , Selenio/toxicidad , Plata/toxicidadRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: [corrected] Fumaria parviflora Lam. is used for treating aches and pains, diarrhea, fever, influenza and other complications. The herb mixed with honey is taken to prevent vomiting as per Ayurvedic text. AIM OF THE STUDY: In vivo studies were conducted to explore the hepatoprotective potential of Fumaria parviflora Lam. Fp extract against nimesulide induced oxidative stress and regulation of critical events in mitochondria mediated apoptosis. MATERIALS AND METHODS: Group of Wistar rats were fed with nimesulide for 5 days (80 mg/kg/day, po), another group was pre-treated with Fp extract/silymarin (200mg/kg/day, po) for 5 days followed by nimesulide exposure. Liver serum biomarkers and histopathology were done to assess hepatotoxicity caused by nimesulide. Antioxidant enzymes (SOD, LPO, GPx, GR) were assessed using biochemical assays as well as gene expression by RT-PCR. GSH content and ROS generation was also evaluated using flow cytometry. Key apoptotic markers like phosphatidyl serine externalization, Bax, Bcl-2 translocation, mitochondrial membrane potential, cytochrome c release, caspases (9/3) activation and DNA damage were also observed in all the groups to confirm involvement of mitochondrial pathway. RESULTS: Pre-treatment with Fp extract for 5 days significantly reduced the impact of nimesulide induced toxicity as evident from the serum biomarkers of liver damage and histopathology. It also modulated antioxidant enzymes mRNA expression as well as activity (SOD, glutathione peroxidase, glutathione reductase) and reduced lipid peroxidation during nimesulide toxicity. Nimesulide exposure decreased GSH content (92.9%) and increased reactive oxygen species (9.29 fold) which was attenuated in Fp treated rats. Fp pre-treatment significantly altered key apoptotic events like Bcl2 and Bax translocation, inhibited mitochondrial depolarization, prevented cytochrome c release, caspase-9/caspase-3 activation and DNA damage. CONCLUSION: Our in vivo findings regarding protection accorded by Fp extract against nimesulide toxicity suggest that Fp not only reduced hepatotoxicity but attenuated critical control points of apoptotic cell death.
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Antioxidantes/uso terapéutico , Apoptosis/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Fumaria , Mitocondrias/fisiología , Estrés Oxidativo/efectos de los fármacos , Fitoterapia , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , SulfonamidasRESUMEN
Nordihydroguaiaretic acid (NDGA) is a phenolic antioxidant found in the leaves and twigs of the evergreen desert shrub, Larrea tridentata (Sesse and Moc. ex DC) Coville (creosote bush). It has a long history of traditional medicinal use by the Native Americans and Mexicans. The modulatory effects of topically applied NDGA was studied on acute inflammatory and oxidative stress responses in mouse skin induced by stage I tumor promoting agent, 12-O-tetradecanoylphorbol-13-acetate (TPA). Double TPA treatment adversely altered many of the marker responses of stage I skin tumor promotion cascade. Pretreatment of NDGA in TPA-treated mice mitigated cutaneous lipid peroxidation and inhibited production of hydrogen peroxide. NDGA treatment also restored reduced glutathione level and activities of antioxidant enzymes. Elevated activities of myeloperoxidase, xanthine oxidase and skin edema formation in TPA-treated mice were also lowered by NDGA indicating a restrained inflammatory response. Furthermore, results of histological study demonstrated inhibitory effect of NDGA on cellular inflammatory responses. This study provides a direct evidence of antioxidative and anti-inflammatory properties of NDGA against TPA-induced cutaneous inflammation and oxidative stress corroborating its chemopreventive potential against skin cancer.
RESUMEN
Methotrexate (MTX) is a folic acid antagonist widely used as a cytotoxic chemotherapeutic agent for leukemia and other malignancies. The purpose of this study was to investigate the damage caused by MTX on liver mitochondria and its protection by using antioxidant properties of lipoic acid. MTX substantially affects mitochondrial function by reducing glutathione levels leading to disturbances in antioxidant enzyme defense system. Lipoic acid occurs naturally in mitochondria as a coenzyme. In various studies lipoic acid has been convincingly shown to exhibit an antioxidant role when supplemented exogenously. We studied the effect of lipoic acid pre-treatment on the toxicity of MTX in mouse liver mitochondria focusing specifically on the oxidative stress. MTX caused a significant rise in the mitochondrial lipid peroxidation (LPO), protein carbonyl (PC) content and superoxide radical generation. It also affected the mitochondrial thiol profile. Pre-treatment of mice with lipoic acid (35 mg/kg) markedly lowered mitochondrial LPO, PC content and superoxide radical generation. It also restored decreased enzymatic and non-enzymatic antioxidants of mitochondria. It is suggested that lipoic acid has a potential role in suppressing MTX-induced mitochondrial toxicity, and it affords protection either by reversing the decline of antioxidants or by the directly scavenging the free radicals.
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Antagonistas del Ácido Fólico/toxicidad , Metotrexato/antagonistas & inhibidores , Metotrexato/toxicidad , Mitocondrias Hepáticas/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ácido Tióctico/farmacología , Animales , Peso Corporal/efectos de los fármacos , ADN/metabolismo , Radicales Libres/metabolismo , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Técnicas In Vitro , Metabolismo de los Lípidos/efectos de los fármacos , Ratones , Oxidación-Reducción , Carbonilación Proteica/efectos de los fármacos , Compuestos de Sulfhidrilo/metabolismo , Superóxido Dismutasa/metabolismo , Superóxidos/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
Nimesulide, a popular nonsteroidal anti-inflammatory drug, has been associated with serious hepatotoxicity. Reactive oxygen species (ROS) and mitochondrial perturbations have been implicated in drug induced hepatotoxicity, although their role in the pathway needs exploration. Study was undertaken to elucidate the effect of Fumaria parviflora Lam. (Fp) on nimesulide induced cell death in primary rat hepatocyte cultures. Fp extract treated cells showed increased viability as compared to nimesulide stressed cells as assessed by MTT assay. LDH leakage increased significantly at 500microM nimesulide, and the data suggested that apoptosis was the predominant mechanism responsible for cell death. Nimesulide induced apoptosis was further confirmed by DNA fragmentation and chromatin condensation. Nimesulide exposure increased intracellular ROS, translocation of Bax and Bcl2 followed by mitochondrial depolarization and cytochrome c (Cyt c) release along with caspase-9/-3 activity confirming involvement of mitochondria in nimesulide induced apoptosis. Events like membrane depolarization of mitochondria, expression of Bax, Bcl2, externalization of phosphatidyl serine are substantially reversed by the pre-treatment of Fp extract. Thus, the study indicates that Fp extract modulates critical events regulating pro and anti-apoptotic proteins in mitochondria dependent apoptosis induced by nimesulide.
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Apoptosis/efectos de los fármacos , Fumaria/química , Mitocondrias Hepáticas/efectos de los fármacos , Extractos Vegetales/farmacología , Sulfonamidas/efectos adversos , Animales , Células Cultivadas , Ensamble y Desensamble de Cromatina , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Citocromos c/metabolismo , Fragmentación del ADN/efectos de los fármacos , Genes bcl-2 , Glutatión , Hepatocitos/citología , Hepatocitos/efectos de los fármacos , Peroxidación de Lípido , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Extractos Vegetales/química , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno , Proteína X Asociada a bcl-2RESUMEN
Previous studies on the intertidal copepod Tigriopus japonicus have demonstrated that it is a suitable model species for the assessment of acute toxicities of marine pollutants. In order to standardize T. japonicus for use in environmental risk assessment involving whole life cycle exposure, we tested nine pollutants for their effects on growth and reproduction during a two-generation life cycle exposure test. Nauplii (F 0) were exposed to a range of concentrations of each chemical in a static renewal culture system. Broods of the second generation (F1) were subsequently exposed to the same concentrations for one full life cycle. Of the seven traits (nauplius phase, development time, survival, sex ratio, number of clutch, nauplii per clutch and fecundity), only the length of the nauplius phase and development time showed a greater sensitivity to chemical exposure. Between the two sensitive traits, the period of the nauplius phase was more sensitive than cohort generation time. Biocides significantly increased the maturation period of nauplii as well as copepodids in F 0 generation. In this study, it was demonstrated that T. japonicus could also be used in reproduction and life cycle tests and it provides an opportunity for testing the chronic and subchronic toxic effects of marine pollutants. Further validation and harmonization in a multi-centric study involving other laboratories of the region will strengthen its use as a supplement to existing model species.
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Copépodos/fisiología , Pruebas de Toxicidad , Contaminantes del Agua/toxicidad , Animales , Arsenicales , Interpretación Estadística de Datos , Desinfectantes/toxicidad , Disruptores Endocrinos/toxicidad , Femenino , Dosificación Letal Mediana , Masculino , Reproducción/efectos de los fármacos , Análisis de Supervivencia , Oligoelementos/toxicidadRESUMEN
We cloned and sequenced the full-length cDNA of a theta class glutathione S-transferase (GST-T) from the polychaete Neanthes succinea. The open reading frame of N. succinea GST-T cDNA was 678bp and encoded 226 amino acid residues. We generated recombinant N. succinea GST-T by expression in transformed Escherichia coli and studied the kinetic properties as well as the effects of inhibitors, pH, and temperature on N. succinea GST-T. GST-T expression was studied using real-time RT-PCR in response to exposure to the model oxidative stress-inducing agent, CuCl(2). Copper induced a concentration-dependant increase in the expression of GST-T. Moreover, polychaetes collected from a heavily contaminated lake near an industrial complex showed significantly higher levels of GST-T expression. Interestingly, the site-collected polychaetes with the highest GST-T mRNA expression levels also showed the highest metallothioneins levels. These results suggest that GST-T in polychaetes may have an antioxidant role and that N. succinea GST-T expression may be a useful biomarker for exposure to environmental contaminants such as copper. Our findings provide a better understanding of the biochemical characteristics of N. succinea GST-T, and elucidate the potential role of GST-T in heavy metal-induced oxidative stress and as a biomarker for environmental contamination.
Asunto(s)
Regulación Enzimológica de la Expresión Génica , Glutatión Transferasa/biosíntesis , Glutatión Transferasa/genética , Poliquetos/enzimología , Poliquetos/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Biomarcadores/análisis , Clonación Molecular , Cobre/toxicidad , ADN Complementario/química , Dinitroclorobenceno/metabolismo , Etilmaleimida/farmacología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Sedimentos Geológicos/análisis , Glutatión/metabolismo , Glutatión Transferasa/análisis , Glutatión Transferasa/metabolismo , Hemina/farmacología , Concentración de Iones de Hidrógeno , Datos de Secuencia Molecular , Filogenia , Poliquetos/clasificación , Proteínas Recombinantes/análisis , Proteínas Recombinantes/biosíntesis , Temperatura , Triazinas/farmacología , Contaminantes Químicos del Agua/toxicidadRESUMEN
Natural antioxidants like catechin are now known to have a modulatory role on physiological functions and biotransformation reactions involved in the detoxification process, thereby affording protection from toxic metabolic actions of xenobiotics. Reactive oxygen intermediates have been demonstrated to play an etiological role in anticancer drug-induced toxicity. This study was performed to explore the modulatory and protective effect of catechin on the toxicity of an anticancer drug, tamoxifen (TAM) with special reference to protection against disruption of glutathione metabolizing and antioxidant enzymes. TAM treatment resulted in a significant increase in the lipid peroxidation (LPO), H(2)O(2) generation and protein carbonyl (PC) contents in the liver and kidney as compared to controls while catechin+TAM-treated group showed significant decrease in LPO levels, H(2)O(2) generation and PC contents in liver and kidney when compared with TAM-treated group. Non-enzymatic antioxidants like reduced glutathione (GSH) and low molecular antioxidants like ascorbic acid (AsA) also showed normalcy due to exogenous catechin administration. Catechin pre-treatment showed restoration in the level of cytochrome P450 (CYP) content and in the activities of glutathione metabolizing enzymes, viz., glutathione-S-transferase (GST), glutathione reductase (GR) and glutathione peroxidase (GPx) and other antioxidant enzymes such as, glucose-6-phosphate dehydrogenase (G6-PD), catalase (CAT) and superoxide dismutase (SOD) in both liver and kidney when compared to TAM-treated animals. The results of the study show that catechin supplementation might be helpful in abrogation of TAM toxicity during chemotherapy. Additionally, it makes it a prophylactic and preventive agent of anticancer drug-induced oxidative stress.
Asunto(s)
Antineoplásicos Hormonales/toxicidad , Antioxidantes/farmacología , Catequina/farmacología , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Tamoxifeno/toxicidad , Animales , Ácido Ascórbico/metabolismo , Antagonismo de Drogas , Quimioterapia Combinada , Enzimas/metabolismo , Glutatión/metabolismo , Peróxido de Hidrógeno/metabolismo , Riñón/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Carbonilación Proteica/efectos de los fármacosRESUMEN
Cancer of the prostate gland (CaP), the most common invasive malignancy and a major cause of cancer related deaths in male population in the USA, is an ideal candidate disease for chemoprevention because it is typically detected in elderly population with a relatively slower rate of growth and progression. Many dietary phytochemicals are showing promising chemopreventive effects, at-least in pre-clinical models of CaP. Our published data in cell culture and animal studies, supported by the work from other laboratories, as well as epidemiological observations and case-control studies, suggest that polyphenols present in green tea possess CaP chemopreventive and possibly therapeutic effects. This present study was designed to compare CaP cancer chemopreventive effects of green tea polyphenols (GTP), water extract of black tea, and their major constituents epigallocatechin-3-gallate and theaflavins, respectively, in athymic nude mice implanted with androgen-sensitive human CaP CWR22Rnu1 cells. Our data demonstrated that the treatment with all the tea ingredients resulted in (i) significant inhibition in growth of implanted prostate tumors, (ii) reduction in the level of serum prostate specific antigen, (iii) induction of apoptosis accompanied with upregulation in Bax and decrease in Bcl-2 proteins, and (iv) decrease in the levels of VEGF protein. Furthermore, we also found that GTP (0.01 or 0.05% w/v; given after establishment of CWR22Rnu1 tumor) causes a significant regression of tumors suggesting therapeutic effects of GTP at human achievable concentrations.
Asunto(s)
Anticarcinógenos/farmacología , Biflavonoides/farmacología , Catequina/análogos & derivados , Antígeno Prostático Específico/metabolismo , Neoplasias de la Próstata/prevención & control , Té/química , Animales , Apoptosis/efectos de los fármacos , Catequina/farmacología , Flavonoides/farmacología , Masculino , Ratones , Ratones Desnudos , Fenoles/farmacología , Polifenoles , Antígeno Prostático Específico/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Regulación hacia Arriba , Proteína X Asociada a bcl-2/biosíntesisRESUMEN
Walnut (Juglans regia L.) bark has been claimed to possess anti-inflammatory, blood purifying, anticancer, depurative, diuretic and laxative activities. It contains several therapeutically active constituents, especially polyphenols. We studied the antioxidant potential of aqueous extract of walnut bark and its modulatory effect on cyclophosphamide (CP)-induced urotoxicity in Swiss albino male mice. Free radical-scavenging activity of extract was assessed in four in vitro assays. The phenolic and flavonolic contents of the extract were also measured. Walnut bark extract treatment (150 mg/kg p.o. x 10 days) resulted in protective restoration of decreased antioxidants in CP-treated (18 mg/kg i.p. x 10 days) animals. CP treatment caused decreases in the activities of catalase (CAT), glutathione peroxidase (GP), glutathione reductase (GR) and glutathione S-transferase (GST) and in the glutathione (GSH) content in urinary bladder and a significant concomitant increase in lipid peroxidation (LPO). Administration of extract restored all the antioxidants significantly and lowered the elevated LPO in the bladder. A correlation between radical scavenging capacities of the extract with phenolic content was observed thus justifying its antioxidant potential against oxidative stress-mediated urotoxicity in mice. Walnut is reported to possess antiproliferative activity. Its protective effect on CP-induced toxicity in bladder is a promising activity, which warrants possible clinical investigations on this medicinal plant.