RESUMO
Phthalates metabolites have been detected in the urine of pregnant and breastfeeding women. Thus, this study evaluated the adverse effects of maternal exposure to a mixture of six phthalates (Pth mix) on the mammary gland development and carcinogenesis in F1 female offspring. Pregnant female Sprague-Dawley rats were exposed daily to vehicle or Pth mix (35.22% diethyl-phthalate, 21.03% di-(2-ethylhexyl)-phthalate, 14.91% dibutyl-phthalate, 15.10% diisononyl-phthalate, 8.61% diisobutyl-phthalate, and 5.13% benzylbutyl-phthalate) by gavage at 20 µg/kg, 200 µg/kg or 200 mg/kg during gestational day 10 (GD 10) to postnatal day 21 (PND 21). After weaning (PND 22), some female offspring were euthanized for mammary gland analyses while other females received a single dose of N-methyl-N-nitrosourea (MNU, 50 mg/kg) or vehicle and then tumor incidence and multiplicity were recorded until PND 180. Maternal Pth mix exposure increased the number of Ki-67 and progesterone receptor-positive epithelial cells in the mammary gland from Pth mix 200 at µg/kg and 200 mg/kg groups. In addition, tumor incidence and mean number were higher only in Pth mix at 200 mg/kg when compared to the vehicle-treated group, and percentage of tumor-free animals was lower in Pth mix at 200 µg/kg and 200 mg/kg groups. The findings indicate that perinatal Pth mixture exposure increased susceptibility to MNU-induced mammary carcinogenesis in adult F1 female offspring.
Assuntos
Carcinogênese/induzido quimicamente , Poluentes Ambientais/toxicidade , Neoplasias Mamárias Animais/induzido quimicamente , Ácidos Ftálicos/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Ração Animal , Animais , Relação Dose-Resposta a Droga , Poluentes Ambientais/administração & dosagem , Poluentes Ambientais/classificação , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Metilnitrosoureia/toxicidade , Ácidos Ftálicos/administração & dosagem , Ácidos Ftálicos/classificação , Gravidez , Ratos , Ratos Sprague-Dawley , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismoRESUMO
Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants, commonly used as flame retardants in a wide variety of products. In the last years, the concentration of PBDEs is increasing in the environment, turning human exposure more common. Since the diet is the primary source of human exposure, several surveys evaluate the levels of PBDEs in foods to estimate the dietary intake and the hazard index (HI). However, this data is limited in Brazil. Thus, this study aims to determine the level of seven PBDE congeners (BDE-28, 47, 99, 100, 153, 154, 183) in Brazilian food of animal origin. The total concentration of PBDE (∑PBDE) determined in the food samples were 2.29 (0.92-4.85) ng/g wet weight (ww), 1.98 (1.23-3.12) ng/g ww, 1.91 (1.23-3.12) ng/g ww, and 4.42 (1.26-8.42) ng/g ww in eggs, fish, seafood, and milk, respectively. BDE-47 was the most abundant compound. Based on consumer habits and the found levels of PBDEs in Brazilian food, we estimated the daily intake of ∑PBDEs as 3.25 (0.02-2.19) ng/kg bw per day. Surprisingly, the PBDE levels in milk samples were higher than those found in reported studies in other countries, and the consumption of milk products give a higher relative contribution to PBDEs exposure. The HI was <1. A complete risk assessment of the human exposure to PBDEs most likely could be evaluated considering all commercial PBDEs congeners and other exposure sources of these contaminants.
Assuntos
Ovos/análise , Poluentes Ambientais/toxicidade , Éteres Difenil Halogenados/toxicidade , Leite/química , Alimentos Marinhos/análise , Animais , Brasil , Poluentes Ambientais/administração & dosagem , Poluentes Ambientais/química , Peixes , Análise de Alimentos , Contaminação de Alimentos , Éteres Difenil Halogenados/administração & dosagem , Éteres Difenil Halogenados/química , HumanosRESUMO
We have previously shown that daily exposure to the environmental pollutant 3-methylcholanthrene (3MC) alters the ovarian function by affecting follicle growth and ovulation. To extend our findings, the aims of this work were to study the effects of daily and non-daily exposure to 3MC on oocyte morphology and integrity and the meiosis process. To this end, immature female rats were daily (0.1-1.0 mg/kg) and non-daily (0.1 mg/kg, three times a week) exposed to 3MC and/or α-naphthoflavone (αNF) (80 mg/kg) for 19 and 20 days, respectively. The latter was used to study its ability to prevent the 3MC action. Follicular growth was examined by histology, apoptosis by in situ cell death detection, oocyte integrity by morphological parameters and fluorescent dyes, and the meiotic spindle by immunostaining. Compared with controls (C), and in a dose-dependent manner, all 3MC-treated rats showed i) increased presence of apoptotic cells in antral follicles and decreased percentage of healthy oocytes, ii) increased oocyte area, perimeter and perivitelline space and decreased thickness of the zona pellucida, and ii) increased percentage of oocytes with abnormal meiotic spindle. In addition, the non-daily dose of 3MC caused DNA damage in oocytes, but not in blood or bone marrow cells. All 3MC-induced changes were prevented with the co-treatment with αNF. These results suggest that low doses of 3MC severely disrupt the ovarian function and that germ cells seem to be more sensitive to this environmental pollutant than other cells such as peripheral blood and bone marrow cells.
Assuntos
Benzoflavonas/toxicidade , Metilcolantreno/toxicidade , Oócitos/efeitos dos fármacos , Folículo Ovariano/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Benzoflavonas/administração & dosagem , Células da Medula Óssea/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Poluentes Ambientais/administração & dosagem , Poluentes Ambientais/toxicidade , Feminino , Meiose/efeitos dos fármacos , Metilcolantreno/administração & dosagem , Oócitos/citologia , Ratos , Ratos Sprague-DawleyRESUMO
PURPOSE: Environmental and nutritional disorders during perinatal period cause metabolic dysfunction in the progeny and impair human health. Advanced glycation end products (AGEs) are primarily produced during metabolism of excess blood glucose, which is observed in diabetes. Methylglyoxal (MG) is a precursor for the generation of endogenous AGEs, which disturbs the metabolism. This work aimed to investigate whether the maternal MG treatment during lactation programs the progeny to metabolic dysfunction later in life. METHODS: Female Wistar rats were divided into two groups: control group (C) treated with saline and MG group treated with MG (60 mg/kg/day) by gavage throughout the lactation period. Both mothers and offspring were fed a standard chow. At weaning, breast milk composition was analyzed and mothers euthanized for blood and tissue sample collections. At 90 days of age, offspring were submitted to glucose tolerance test (ivGTT) and euthanized for blood and tissue samples collection. RESULTS: MG mothers showed increase in glucose and fructosamine levels; however, they showed low insulin levels and failure in ß-cell function (p < 0.05). MG mothers also showed dyslipidemia (p < 0.05). Moreover, breast milk had elevated levels of glucose, triglycerides, cholesterol and fructosamine and low insulin (p < 0.05). Interestingly, MG offspring had increased body weight and adipose tissue at adulthood, and they also showed glucose intolerance and failure in ß-cell function (p < 0.05). Besides, MG offspring showed dyslipidemia (p < 0.05) increasing cardiovascular diseases risk. CONCLUSIONS: Maternal MG treatment negatively affects the male rat offspring, leading to type 2 diabetes and dyslipidemia in later life, possibly by changes in breast milk composition.
Assuntos
Diabetes Mellitus Tipo 2/induzido quimicamente , Dislipidemias/induzido quimicamente , Poluentes Ambientais/toxicidade , Lactação/efeitos dos fármacos , Exposição Materna/efeitos adversos , Obesidade/induzido quimicamente , Aldeído Pirúvico/toxicidade , Adiposidade/efeitos dos fármacos , Administração Oral , Animais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Dislipidemias/sangue , Dislipidemias/metabolismo , Dislipidemias/patologia , Poluentes Ambientais/administração & dosagem , Poluentes Ambientais/análise , Feminino , Insulina/análise , Insulina/sangue , Insulina/metabolismo , Resistência à Insulina , Secreção de Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/patologia , Lactação/metabolismo , Masculino , Leite/química , Obesidade/sangue , Obesidade/metabolismo , Obesidade/patologia , Gravidez , Aldeído Pirúvico/administração & dosagem , Aldeído Pirúvico/análise , Distribuição Aleatória , Ratos Sprague-Dawley , Toxicocinética , Aumento de Peso/efeitos dos fármacosRESUMO
Tributyltin chloride (TBT) is an organometallic pollutant that is used as a biocide in antifouling paints. TBT induces several toxic and endocrine-disrupting effects. However, studies evaluating the effects of TBT on renal function are rare. This study demonstrates that TBT exposure is responsible for improper renal function as well as the development of abnormal morphophysiology in mammalian kidneys. Female rats were treated with TBT, and their renal morphophysiology was assessed. Morphophysiological abnormalities such as decreased glomerular filtration rate and increased proteinuria levels were observed in TBT rats. In addition, increases in inflammation, collagen deposition and α-smooth muscle actin (α-SMA) protein expression were observed in TBT kidneys. A disrupted cellular redox balance and apoptosis in kidney tissue were also observed in TBT rats. TBT rats demonstrated reduced serum estrogen levels and estrogen receptor-α (ERα) protein expression in renal cortex. Together, these data provide in vivo evidence that TBT is toxic to normal renal function and that these effects may be associated with renal histopathology complications, such as inflammation and fibrosis.
Assuntos
Desinfetantes/toxicidade , Poluentes Ambientais/toxicidade , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Insuficiência Renal/induzido quimicamente , Compostos de Trialquitina/toxicidade , Actinas/agonistas , Actinas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Biomarcadores/sangue , Biomarcadores/metabolismo , Biomarcadores/urina , Colágeno/agonistas , Colágeno/metabolismo , Desinfetantes/administração & dosagem , Relação Dose-Resposta a Droga , Disruptores Endócrinos/toxicidade , Poluentes Ambientais/administração & dosagem , Receptor alfa de Estrogênio/antagonistas & inibidores , Receptor alfa de Estrogênio/metabolismo , Estrogênios/sangue , Feminino , Fibrose , Rim/imunologia , Rim/patologia , Rim/fisiopatologia , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Mastócitos/patologia , Proteinúria/etiologia , Ratos Wistar , Insuficiência Renal/imunologia , Insuficiência Renal/patologia , Insuficiência Renal/fisiopatologia , Estanho/sangue , Toxicocinética , Compostos de Trialquitina/administração & dosagemRESUMO
The aim of this work was to study whether the increase in antioxidant defenses associated with orchiectomy may account for the reduced susceptibility to aluminum (Al) in male kidney and also to examine whether the reduced antioxidant defenses are associated with androgen levels in orchiectomized (ORX) rats treated with testosterone propionate (TP). Rats were divided into nine groups, namely, intact males (without treatment, treated with sodium lactate, and treated with Al), sham males, ORX males (without treatment, treated with sodium lactate, treated with TP, treated with Al, and treated with TP and Al). Al groups were chronically treated with aluminum lactate for 12 weeks (0.575 mg Al/100 g of body weight, intraperitoneally, three times per week). We reported that ORX rats treated with Al had significantly less lipid peroxidation and an increased level of reduced glutathione (GSH) and GSH/oxidized glutathione ratio in the kidney when compared with intact and TP-treated ORX rats. The activity of superoxide dismutase, catalase, and glutathione peroxidase in ORX rats was much greater than in intact or TP-administered ORX rats. Castration reduced the glomerular alterations caused by Al as well as the number of necrotic tubular cells and nuclear abnormalities. However, we observed a slight alteration in brush border, dilation of proximal tubules, mononuclear infiltrates, and interstitial fibrosis. Castrated males treated with TP showed that this intervention cancels the protective effect of the ORX. This finding suggests that androgens contribute to the development of renal alterations and proteinuria in rats treated with Al. Our results showed that ORX rats are protected against the induction of oxidative stress by Al, but the morphological damage to the kidney tissue induced by the cation was only reduced. Male intact rats treated with Al had more severe glomerulosclerosis, tubular damage, and proteinuria than ORX rats.
Assuntos
Alumínio/toxicidade , Poluentes Ambientais/toxicidade , Intoxicação por Metais Pesados , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Intoxicação/fisiopatologia , Testículo/metabolismo , Testosterona/metabolismo , Alumínio/administração & dosagem , Animais , Resistência a Medicamentos , Poluentes Ambientais/administração & dosagem , Glutationa/metabolismo , Terapia de Reposição Hormonal/efeitos adversos , Injeções Intraperitoneais , Rim/metabolismo , Rim/patologia , Rim/fisiopatologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Metais Pesados/sangue , Metais Pesados/metabolismo , Orquiectomia/efeitos adversos , Oxirredução , Oxirredutases/metabolismo , Intoxicação/sangue , Intoxicação/metabolismo , Intoxicação/patologia , Distribuição Aleatória , Ratos Wistar , Insuficiência Renal/etiologia , Insuficiência Renal/prevenção & controle , Testículo/efeitos dos fármacos , Testículo/fisiopatologia , Testosterona/efeitos adversos , Testosterona/sangue , Testosterona/uso terapêuticoRESUMO
Cadmium (Cd) is a well-known toxicant targeting many organs, among them placenta. This heavy metal also has embryonary and foetal toxicity. This study was undertaken to analyse the effect of a single Cd dose administered at 4, 7, 10 or 15 days of gestation on the offspring of pregnant rats sacrificed at 20 days of gestation. Cadmium chloride was administered subcutaneously at 10 mg/kg body weight to Wistar pregnant dams; control animals received a proportionate volume of sterile normal saline by the same route. Maternal uteri, livers, kidneys and lungs, and foetuses were examined at necropsy. Samples of maternal organs and whole foetuses were collected for histopathologic examination, determination of Cd levels and staining by the Alizarin red S technique. Results revealed a clear embryotoxic and a teratogenic effect of this heavy metal, the former as a significant increase in the number of resorptions, and the latter as significant decrease of the gestational sac weight, and the size and weight of foetuses of Cd-treated dams as well as induced malformations in skull bones, vertebrae and thoracic, and pelvian limbs. The deleterious effects found were similar to those previously reported for other animal models suggesting a high conservation of the pathogenic mechanisms of Cd. Additionally, many of the addressed aspects showed a slight dependence on the time of administration of the toxic that might be due to the accumulation of the metal in different organs, as we were able to demonstrate by the analysis of its concentration.
Assuntos
Cloreto de Cádmio/toxicidade , Poluentes Ambientais/toxicidade , Feto/anormalidades , Efeitos Tardios da Exposição Pré-Natal , Animais , Cloreto de Cádmio/administração & dosagem , Poluentes Ambientais/administração & dosagem , Feminino , Feto/efeitos dos fármacos , Gravidez , Ratos , Ratos WistarRESUMO
Diphenyl ditelluride (PhTe)2 is a versatile molecule used in the organic synthesis and it is a potential prototype for the development of novel biologically active molecules. The mechanism(s) involved in (PhTe)2 toxicity is(are) elusive, but thiol oxidation of critical proteins are important targets. Consequently, the possible remedy of its toxicity by thiol-containing compounds is of experimental and clinical interest. The present study aimed to investigate putative mechanisms underlying the toxicity of (PhTe)2 in vivo. We assessed behavioral and oxidative stress parameters in mice, including the modulation of antioxidant enzymatic defense systems. In order to mitigate such toxicity, N-acetylcysteine (NAC) was administered before (3 d) and simultaneously with (PhTe)2 (7 d). Mice were separated into six groups receiving daily injections of (1) TFK (2.5 ml/kg, intraperitonealy (i.p.)) plus canola oil (10 ml/kg, subcutaneously (s.c.)), (2) NAC (100 mg/kg, i.p.) plus canola oil s.c., (3) TFK i.p. plus (PhTe)2 (10 µmol/kg, s.c.), (4) TFK i.p. plus (PhTe)2 (50 µmol/kg, s.c.), (5) NAC plus (PhTe)2 (10 µmol/kg, s.c.), and (6) NAC plus (PhTe)2 (50 µmol/kg, s.c.). (PhTe)2 treatment started on the fourth day of treatment with NAC. Results demonstrated that (PhTe)2 induced behavioral alterations and inhibited important selenoenzymes (thioredoxin reductase and glutathione peroxidase). Treatments produced no or minor effects on the activities of antioxidant enzymes catalase and glutathione reductase. Contrary to expected, NAC co-administration did not protect against the deleterious effects of (PhTe)2. Other low-molecular-thiol containing molecules should be investigated to determine whether or not they can be effective against ditellurides.
Assuntos
Derivados de Benzeno/toxicidade , Poluentes Ambientais/toxicidade , Glutationa Peroxidase/antagonistas & inibidores , Proteínas do Tecido Nervoso/antagonistas & inibidores , Síndromes Neurotóxicas/enzimologia , Compostos Organometálicos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores , Acetilcisteína/administração & dosagem , Acetilcisteína/uso terapêutico , Animais , Antioxidantes/administração & dosagem , Antioxidantes/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Derivados de Benzeno/administração & dosagem , Derivados de Benzeno/antagonistas & inibidores , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Relação Dose-Resposta a Droga , Poluentes Ambientais/administração & dosagem , Poluentes Ambientais/antagonistas & inibidores , Glutationa Peroxidase/metabolismo , Injeções Intraperitoneais , Injeções Subcutâneas , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Síndromes Neurotóxicas/prevenção & controle , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/antagonistas & inibidores , Tiorredoxina Dissulfeto Redutase/metabolismo , Testes de Toxicidade AgudaRESUMO
Environmental contaminants known as endocrine-disrupting chemicals (EDC) have been associated with adverse effects on reproductive processes. These chemicals may mimic or antagonize endogenous hormones, disrupting reproductive functions. Although preliminary studies focused on environmental estrogens, the presence of compounds with androgenic activity has also been described. This study examines exposure of female pregnant and lactating rats to low doses of androgens and assesses potential effects on female offspring. Pregnant Wistar rats were exposed to testosterone propionate (TP) at doses of 0.05, 0.1, or 0.2 mg/kg or corn oil (vehicle), subcutaneously, to determine influence on reproductive health of female offspring. There were two exposure groups: (1) rats treated from gestational day (GD) 12 until GD 20; and (2) animals treated from GD 12 until the end of lactation. Perinatal exposure to TP produced increased anogenital distance after birth and diminished height of uterine glandular epithelium at puberty in animals exposed to 0.2 mg/kg. However, these alterations were not sufficient to impair sexual differentiation and normal physiology of the female rat reproductive tract.
Assuntos
Androgênios/toxicidade , Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Lactação , Efeitos Tardios da Exposição Pré-Natal , Desenvolvimento Sexual/efeitos dos fármacos , Anormalidades Urogenitais/induzido quimicamente , Androgênios/administração & dosagem , Animais , Relação Dose-Resposta a Droga , Disruptores Endócrinos/administração & dosagem , Endométrio/anormalidades , Endométrio/efeitos dos fármacos , Poluentes Ambientais/administração & dosagem , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Injeções Subcutâneas , Exposição Materna/efeitos adversos , Gravidez , Distribuição Aleatória , Ratos , Ratos Wistar , Teratogênicos/toxicidade , Propionato de Testosterona/administração & dosagem , Propionato de Testosterona/toxicidadeRESUMO
Methylmercury (MeHg) is a highly toxic environmental contaminant that produces neurological and developmental impairments in animals and humans. Although its neurotoxic properties have been widely reported, the molecular mechanisms by which MeHg enters the cells and exerts toxicity are not yet completely understood. Taking into account that MeHg is found mostly bound to sulfhydryl-containing molecules such as cysteine in the environment and based on the fact that the MeHg-cysteine complex (MeHg-S-Cys) can be transported via the L-type neutral amino acid carrier transport (LAT) system, the potential beneficial effects of L-methionine (L-Met, a well known LAT substrate) against MeHg (administrated as MeHg-S-Cys)-induced neurotoxicity in mice were investigated. Mice were exposed to MeHg (daily subcutaneous injections of MeHg-S-Cys, 10 mg Hg/kg) and/or L-Met (daily intraperitoneal injections, 250 mg/kg) for 10 consecutive days. After treatments, the measured hallmarks of toxicity were mostly based on behavioral parameters related to motor performance, as well as biochemical parameters related to the cerebellar antioxidant glutathione (GSH) system. MeHg significantly decreased motor activity (open-field test) and impaired motor performance (rota-rod task) compared with controls, as well as producing disturbances in the cerebellar antioxidant GSH system. Interestingly, L-Met administration did not protect against MeHg-induced behavioral and cerebellar changes, but rather increased motor impairments in animals exposed to MeHg. In agreement with this observation, cerebellar levels of mercury (Hg) were higher in animals exposed to MeHg plus L-Met compared to those only exposed to MeHg. However, this event was not observed in kidney and liver. These results are the first to demonstrate that L-Met enhances cerebellar deposition of Hg in mice exposed to MeHg and that this higher deposition may be responsible for the greater motor impairment observed in mice simultaneously exposed to MeHg and L-Met.
Assuntos
Cerebelo/química , Cisteína/análogos & derivados , Poluentes Ambientais/toxicidade , Metionina/farmacologia , Compostos de Metilmercúrio/toxicidade , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Desempenho Psicomotor/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Cerebelo/metabolismo , Cisteína/administração & dosagem , Cisteína/farmacocinética , Cisteína/toxicidade , Esquema de Medicação , Poluentes Ambientais/administração & dosagem , Poluentes Ambientais/farmacocinética , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Injeções Intraperitoneais , Masculino , Metionina/administração & dosagem , Compostos de Metilmercúrio/administração & dosagem , Compostos de Metilmercúrio/farmacocinética , Camundongos , Fármacos Neuroprotetores/administração & dosagem , Distribuição AleatóriaRESUMO
It has been hypothesized that oils containing high levels of omega-3 polyunsaturated fatty acids, such as canola and fish oil, could counteract some of the adverse effects induced by phthalates. In the present study, the influence of different oily vehicles on di-butyl phthalate (DBP)-induced testicular toxicity and lipid profile was investigated. Pregnant Wistar rats were treated by oral gavage from gestation days 13 to 20 with DBP (500 mg/kg/day) diluted in three different vehicles: corn, canola or fish oil. Male fetuses were analyzed on gestation day 20. DBP exposure lowered intratesticular testosterone levels and anogenital distance, regardless of the vehicle used. The percentage of seminiferous cords containing multinucleated gonocytes and cord diameter was increased in DBP-exposed groups, compared with vehicle controls, with no difference between the three DBP-exposed groups. Clustering of Leydig cells was seen in all DBP groups. Lipid profile indicated that administration of canola and fish oil can increase the content of omega-3 fatty acids in rat testis. However, content of omega-3 was diminished in DBP-treated groups. Overall, our results indicate that different oily vehicles did not alter fetal rat testicular toxicity induced by a high DBP dose.
Assuntos
Dibutilftalato/toxicidade , Disruptores Endócrinos/toxicidade , Ácidos Graxos Ômega-3/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Exposição Materna/efeitos adversos , Veículos Farmacêuticos/metabolismo , Testículo/efeitos dos fármacos , Animais , Óleo de Milho/química , Óleo de Milho/metabolismo , Dibutilftalato/administração & dosagem , Disruptores Endócrinos/administração & dosagem , Poluentes Ambientais/administração & dosagem , Poluentes Ambientais/toxicidade , Ácidos Graxos Monoinsaturados/química , Ácidos Graxos Monoinsaturados/metabolismo , Ácidos Graxos Ômega-3/química , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Óleos de Peixe/química , Óleos de Peixe/metabolismo , Masculino , Veículos Farmacêuticos/química , Plastificantes/administração & dosagem , Plastificantes/toxicidade , Gravidez , Óleo de Brassica napus , Ratos , Processos de Determinação Sexual/efeitos dos fármacos , Testículo/embriologia , Testículo/metabolismo , Testosterona/metabolismoRESUMO
Reactive O2 species production triggered by particulate matter (PM) exposure is able to initiate oxidative damage mechanisms, which are postulated as responsible for increased morbidity along with the aggravation of respiratory diseases. The aim of this work was to quantitatively analyse the major sources of reactive O2 species involved in lung O2 metabolism after an acute exposure to Residual Oil Fly Ashes (ROFAs). Mice were intranasally instilled with a ROFA suspension (1.0mg/kg body weight), and lung samples were analysed 1h after instillation. Tissue O2 consumption and NADPH oxidase (Nox) activity were evaluated in tissue homogenates. Mitochondrial respiration, respiratory chain complexes activity, H2O2 and ATP production rates, mitochondrial membrane potential and oxidative damage markers were assessed in isolated mitochondria. ROFA exposure was found to be associated with 61% increased tissue O2 consumption, a 30% increase in Nox activity, a 33% increased state 3 mitochondrial O2 consumption and a mitochondrial complex II activity increased by 25%. During mitochondrial active respiration, mitochondrial depolarization and a 53% decreased ATP production rate were observed. Neither changes in H2O2 production rate, nor oxidative damage in isolated mitochondria were observed after the instillation. After an acute ROFA exposure, increased tissue O2 consumption may account for an augmented Nox activity, causing an increased O2(-) production. The mitochondrial function modifications found may prevent oxidative damage within the organelle. These findings provide new insights to the understanding of the mechanisms involving reactive O2 species production in the lung triggered by ROFA exposure.
Assuntos
Cinza de Carvão/toxicidade , Poluentes Ambientais/toxicidade , Pulmão/metabolismo , Mitocôndrias/metabolismo , NADPH Oxidases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Administração Intranasal , Animais , Cinza de Carvão/administração & dosagem , Poluentes Ambientais/administração & dosagem , Feminino , Pulmão/efeitos dos fármacos , Pulmão/enzimologia , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/enzimologiaRESUMO
Hydroquinone (HQ) is an environmental contaminant which causes immune toxicity. In this study, the effects of exposure to low doses of HQ on neutrophil mobilization into the LPS-inflamed lung were investigated. Male Swiss mice were exposed to aerosolized vehicle (control) or 12.5, 25 or 50ppm HQ (1h/day for 5 days). One hour later, oxidative burst, cell cycle, DNA fragmentation and adhesion molecules expressions in circulating neutrophils were determined by flow cytometry, and plasma malondialdehyde (MDA) levels were measured by HPLC. Also, 1h later the last exposures, inflammation was induced by LPS inhalation (0.1mg/ml/10min) and 3h later, the numbers of leukocytes in peripheral blood and in the bronchoalveolar lavage fluid (BALF) were determined using a Neubauer chamber and stained smears; adhesion molecules expressed on lung microvessel endothelial cells were quantified by immunohistochemistry; myeloperoxidase (MPO) activity was measured in the lung tissue by colorimetric assay; and cytokines in the BALF were determined by ELISA. In vivo HQ exposure augmented plasma MDA levels and oxidative activity of neutrophils, but did not cause alterations in cell cycle and DNA fragmentation. Under these conditions, the number of circulating leukocytes was not altered, but HQ exposure reduced LPS-induced neutrophil migration into the alveolar space, as these cells remained in the lung tissue. The impaired neutrophil migration into BALF may not be dependent on reduced cytokines secretions in the BALF and lung endothelial adhesion molecules expressions. However, HQ exposure increased the expression of ß(2) and ß(3) integrins and platelet-endothelial cell adhesion molecule-1 (PECAM-1) in neutrophils, which were not further enhanced by fMLP in vitro stimulation, indicating that HQ exposure activates circulating neutrophils, impairing further stimulatory responses. Therefore, it has been shown, for the first time, that neutrophils are target of lower levels of in vivo HQ exposure, which may be considered in host defense in infectious diseases.
Assuntos
Poluentes Ambientais/toxicidade , Hidroquinonas/toxicidade , Inflamação/fisiopatologia , Pulmão/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Animais , Líquido da Lavagem Broncoalveolar , Moléculas de Adesão Celular/efeitos dos fármacos , Moléculas de Adesão Celular/metabolismo , Movimento Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Poluentes Ambientais/administração & dosagem , Citometria de Fluxo , Hidroquinonas/administração & dosagem , Lipopolissacarídeos/toxicidade , Pulmão/patologia , Masculino , Camundongos , Neutrófilos/metabolismo , Explosão Respiratória/efeitos dos fármacosRESUMO
The present studies were conducted to changes arising from mercury poisoning in the central nervous system (CNS), with a focus on determining the receptors and neurotransmitters involved. Currently, little is known regarding the neurological basis of the cardiopulmonary effects of mercury poisoning. We evaluated changes in systolic arterial pressure (SAP), diastolic arterial pressure (DAP), respiratory rate (RR) and heart rate (HR) following a 5 µl intracisternal (i.c) injection of mercuric chloride (HgCl(2)) and the participation of the autonomic nervous system in these responses. 58 animals were utilized and distributed randomly into 10 groups and administered a 5 µL intracisternal injection of 0.68 µg/kg HgCl(2) (n=7), 1.2 µg/kg HgCl(2) (n=7), 2.4 µg/kg HgCl(2) (n=7), 60 µg/kg HgCl(2) (n=7), 120 µg/kg HgCl(2) (n=3), saline (control) (n=7), 60 µg/kg HgCl(2) plus prazosin (n=6), saline plus prazosin (n=6), 60 µg/kg HgCl(2) plus metilatropina (n=4) or saline plus metilatropina (n=4)HgCl(2). Anesthesia was induced with halothane and maintained as needed with urethane (1.2 g/kg) administered intravenously (i.v.) through a cannula placed in the left femoral vein. The left femoral artery was also cannulated to record systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and heart rate (HR). A tracheotomy was performed to record respiratory rate. Animals were placed in a stereotaxic frame, and the cisterna magna was exposed. After a stabilization period, solutions (saline or HgCl(2)) were injected i.c., and cardiopulmonary responses were recorded for 50 min. Involvement of the autonomic nervous system was assessed through the i.v. injection of hexamethonium (20 mg/kg), prazosin (1 mg/kg) and methylatropine (1 mg/kg) 10 min before the i.c. injection of HgCl(2) or saline. Treatment with 0.68, 1.2, 2.4 µg/kg HgCl(2) or saline did not modify basal cardiorespiratory parameters, whereas the 120 µg/kg dose induced acute toxicity, provoking respiratory arrest and death. The administration of 60 µg/kg HgCl(2), however, induced significant increases (p<0.05) in SAP at the 30°, 40° and 50° min, timepoints and DAP at the 5°, 10°, 20°, 30°, 40° and 50° timepoints. RR was significantly decreased at the 5°, 10°, 20°, 40° and 50° min timepoints; however, there was no change in HR. Hexamethonium administration, which causes non-specific inhibition of the autonomic nervous system, abolished the observed cardiorespiratory effects. Similarly, prazosin, a α(1)-adrenoceptor blocker that specifically inhibits sympathetic nervous system function, abolished HgCl(2) induced increases in SAP and DAP without affecting HR and RR. Methylatropine (1 mg/Kg), a parasympathetic nervous system inhibitor, exacerbated the effects of HgCl(2) and caused slow-onset respiratory depression, culminating in respiratory arrest and death. Our results demonstrate that increases in SAP and DAP induced by the i.c. injection of mercuric chloride are mediated by activation of the sympathetic nervous system.
Assuntos
Sistema Nervoso Autônomo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Cisterna Magna/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Frequência Cardíaca/efeitos dos fármacos , Cloreto de Mercúrio/toxicidade , Intoxicação do Sistema Nervoso por Mercúrio/etiologia , Taxa Respiratória/efeitos dos fármacos , Antagonistas de Receptores Adrenérgicos alfa 1/administração & dosagem , Análise de Variância , Animais , Sistema Nervoso Autônomo/fisiopatologia , Cisterna Magna/fisiopatologia , Relação Dose-Resposta a Droga , Poluentes Ambientais/administração & dosagem , Masculino , Cloreto de Mercúrio/administração & dosagem , Intoxicação do Sistema Nervoso por Mercúrio/fisiopatologia , Intoxicação do Sistema Nervoso por Mercúrio/prevenção & controle , Microinjeções , Antagonistas Nicotínicos/administração & dosagem , Parassimpatolíticos/administração & dosagem , Ratos , Ratos Wistar , Fatores de TempoRESUMO
Manganese (Mn) has a natural occurrence and is necessary during the initial periods of the development. However, in high concentrations, Mn can be related to neurodegenerative disorders. The aim of the present study was to evaluate the mutagenic potential of manganese chloride (MnCl2.4H2O). Comet assay and chromosome aberrations analysis were applied to determine the DNA-damaging and clastogenic effects of MnCl2.4H2O. Cultured human lymphocytes were treated with 15, 20 and 25 microM manganese chloride during the G1, G1/S, S (pulses of 1 and 6h), and G2 phases of the cell cycle. All tested concentrations were cytotoxic and reduced significantly the mitotic index in G1, G1/S and S (1 and 6h) treatments, while in G2 treatment only the higher concentrations (20 and 25 microM) showed cytotoxic effects. Clastogenicity and DNA damage were found only in treatments with the highest concentration (25 microM). Chromosome aberrations were found exclusively in the G2 phase of the cell cycle. The absence of polyploidy in mitosis, suggests that manganese does not affect the formation of the mitotic spindle with the concentrations tested. The genotoxicity found in G2 phase and in the comet assay can be related to the short time of treatment in both cases.
Assuntos
Ciclo Celular/efeitos dos fármacos , Cloretos/toxicidade , Poluentes Ambientais/toxicidade , Linfócitos/efeitos dos fármacos , Células Cultivadas , Cloretos/administração & dosagem , Aberrações Cromossômicas/efeitos dos fármacos , Ensaio Cometa , Poluentes Ambientais/administração & dosagem , Humanos , Linfócitos/metabolismo , Compostos de Manganês/administração & dosagem , Índice Mitótico , Testes de Mutagenicidade , Mutagênicos/administração & dosagem , Mutagênicos/toxicidade , Fatores de TempoRESUMO
Treatment of male Wistar rats with hexachlorobenzene (HCB) (1000 mg/kg b.w.) for 3-30 days decreases circulating levels of thyroxine (T4) but does not affect triiodothyronine (T3). Time courses were determined for 5' deiodinase type I (5' D-I) activity in thyroid, liver, and kidney and 5' deiodinase type II (5' D-II) activity in brown adipose tissue (BAT) to test the possibility that increased deiodinase activity might contribute to the maintenance of the serum T3 level. Specific 5' D-I activity was increased in the thyroid at 21 days and thereafter. No significant changes were observed in the liver, however, total 5' D-I activity in this tissue was increased at 30 days of treatment as a consequence of liver weight enhancement. HCB decreased kidney 5' D-I activity after 15 days, and BAT 5' D-II activity after 21 days of treatment. Total body 5' D-I activity was significantly increased by 30 days of HCB-treatment. HCB increased the activity of hepatic T4 uridine diphosphoglucuronosyl transferase (UDPGT) in a time-dependent manner, without changes in T3 UDPGT. We propose that increased T4 to T3 conversion in the thyroid and in the greatly enlarged liver may account for the maintenance of serum T3 concentration in hypothyroxinemic HCB-treated rats.
Assuntos
Poluentes Ambientais/toxicidade , Hexaclorobenzeno/toxicidade , Iodeto Peroxidase/metabolismo , Doenças da Glândula Tireoide/induzido quimicamente , Glândula Tireoide/efeitos dos fármacos , Hormônios Tireóideos/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/enzimologia , Administração Oral , Animais , Poluentes Ambientais/administração & dosagem , Fungicidas Industriais/administração & dosagem , Expressão Gênica/efeitos dos fármacos , Glucuronosiltransferase/metabolismo , Hexaclorobenzeno/administração & dosagem , Iodeto Peroxidase/genética , Rim/efeitos dos fármacos , Rim/enzimologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Doenças da Glândula Tireoide/sangue , Glândula Tireoide/enzimologia , Hormônios Tireóideos/análiseRESUMO
Xenobiotic estrogens in the environment or diet have received much attention as a possible source of certain hormonal disease states in human and wildlife. Therefore, the detection of estrogenic activity of any substance, especially those related to the food industry, is important. The estrogenic activity of p-hydroxybenzoic acid (PHBA), a compound related to a commonly used group of preservatives in food, cosmetic, and pharmaceutical preparations, was evaluated with immature and adult ovariectomized female mice (CD1) using two well-known bioassays. Subcutaneous administrations (s.c.) of different doses of PHBA were compared with estradiol (E2), and their effects on vaginal cornification and uterotrophic activities were evaluated. Different groups of animals were treated s.c. daily for 3 days with vehicle (corn oil, 0.3 ml/100 g), E2 (1 microgram/100 g), and PHBA (0.5, 5, 50, and 500 micrograms/100 g). Four days after treatment, PHBA produced a dose-dependent response on vaginal cornification and uterotrophic activity in both immature and adult ovariectomized mice. The relative uterotrophic potency of PHBA (500 micrograms/100 g) to E2 (1 microgram/100 g) was 0.0011 in immature mice and 0.0018 in ovariectomized animals.