RESUMO
Manganese (Mn) is a metal and important micronutrient. However, exposure to supraphysiological levels of Mn, which occur through fungicides, atmospheric emissions, drainages, and spills, has been related to health risks, including morphometric changes in the male reproductive organs and impairment on gametogenesis and sperm quality, impacting the fertile ability of adult animals. Despite the relevance of the fetal/perinatal period for toxicological studies on Mn, previous data only deal with the physical and neurological development of the offspring, without mentioning their reproductive development. The present study investigated whether exposure to Mn during fetal/perinatal phase, specifically during the period of formation and proliferation of Sertoli cells, impairs the reproductive development of male offspring in early postnatal life. Therefore, pregnant Wistar rats were randomly distributed into 3 experimental groups: Ctl (received saline solution), Mn-9 (received 9 mg/kg of MnCl2), and Mn-90 (received 90 mg/kg of MnCl2). The female rats received the experimental treatment by gavage from gestational day 13 to lactational day 15, i.e., postnatal day (PND) 15 of the pups. Oxidative damage to the genetic material of germ and Sertoli cells, together with a decrease in connexin 43 immunolabeling were observed in the testis of male pups evaluated at PND 15. In addition, an increase in the seminiferous tubules presenting slight epithelium vacuolization and cells with eosinophilic cytoplasm were observed, without apparent epididymal changes. In conclusion, it was demonstrated that Mn perturbed the initial testicular development by altering Sertoli cell integrity through oxidative insult, which may compromise the spermatogenesis in the long-term.
Assuntos
Manganês , Células de Sertoli , Gravidez , Ratos , Masculino , Animais , Feminino , Ratos Wistar , Sêmen , Testículo , Espermatogênese , Proliferação de CélulasRESUMO
Green propolis produced by Apis melífera bees, having Baccharis dracunculifolia D.C. (Asteraceae) as the primary botanical source, has been used in traditional medicine to treat numerous disorders. However, studies evaluating propolis' potential in treating cardiovascular diseases via its effects on cholesterol metabolism are lacking. Therefore, this study investigated the effects of green propolis extracts on lipid metabolism in hypercholesterolemic guinea pigs. Chemical characterization of ethanolic extracts of green propolis samples was undertaken using HPLC. The in vitro characterization included an evaluation of the antioxidant capacity of the hydroalcoholic extract of green propolis (DPPH and FRAP assays) and its ability to act as an inhibitor of the HMG-CoA reductase enzyme. In vivo, we investigated the effect of the hydroalcoholic extract of green propolis on lipid metabolism in hypercholesterolemic guinea pigs. Results obtained validated previous reports of significant antioxidant activity. HPLC analysis confirmed that coumaric acid, artepillin C, and baccharin were the most common and abundant compounds in green propolis samples among the studied compounds. Furthermore, the compounds in these extracts acted as effective HMG-CoA reductase inhibitors in vitro. In vivo assays demonstrated that a hypercholesterolemic diet significantly reduced serum levels of the HDL cholesterol fraction. Simvastatin and propolis hydroalcoholic extracts promoted a significant increase in HDL cholesterol, suggesting that these extracts can improve the serum lipid profile of hypercholesterolemic guinea pigs. Results obtained in this study provide a perspective on the possible hypocholesterolemic effect of green propolis, suggesting that it can improve the serum lipid profile in hypercholesterolemic guinea pigs.
Assuntos
Própole , Cobaias , Animais , Própole/química , Brasil , HDL-Colesterol , Extratos Vegetais/farmacologia , Antioxidantes , Metabolismo dos Lipídeos , HomeostaseRESUMO
The management of agrochemicals in Brazilian agriculture impacts global environmental sustainability and food security, since this country is one of the major agro-food exporters in the world. Acephate, carbendazim, and dithiocarbamates (DTCs) such as mancozeb, are among the most detected agrochemicals in Brazilian agro-food products, occurring in combination in several crops, especially in fruit cultures. The present study evaluated the impact of the exposure to isolated agrochemicals and all the combined possible mixtures (binary and ternary forms) on the reproductive parameters of male juvenile rats, known to be a vulnerable biological system and developmental window. Data were analyzed using Generalized Linear Models (GzLM), considering each agrochemical as an independent factor. The study revealed higher reproductive toxicity exerted by isolated agrochemicals when compared to the combined treatments, which exhibited mostly an antagonistic effect. Results suggest endocrine disruptive effects of each one separately on the weight of reproductive organs and testicular histomorphometry, besides changes in testicular SOD activity. The full factorial experimental design employed here allowed us to conclude that it is not possible to scale-up the effects of the isolated treatments to the mixtures, showing how difficult it is to know beforehand the response and cross-talk among the multiple physiological mechanisms disturbed by complex mixtures. Considering that food products are shared on a global scale and that some of these three agrochemicals have already been prohibited in EU countries, the consumption of some Brazilian products puts global human health at risk, that of children.
Assuntos
Agroquímicos/toxicidade , Disruptores Endócrinos/toxicidade , Animais , Brasil , Misturas Complexas , Modelos Lineares , Masculino , Ratos , Testes de ToxicidadeRESUMO
The widespread use of agrochemicals results in the exposure of the general human population, including children, to several of these chemicals simultaneously. In the present preclinical study, it was investigated the hepatic damages caused by exposure to acephate, carbendazim and mancozeb when administered alone or in different combinations (binary and ternary). Juvenile male Wistar rats were exposed to agrochemicals from post-natal day 53, by gavage. The doses of agrochemicals applied here were determined from previous studies whose results showed no signs of systemic toxicity. All exposures provoked a significant increase in DNA damage (except for acephate alone) and activation of the xenobiotic biotransformation system (except for the ternary mixture). Interestingly, the ternary mixture did not exhibit an exacerbation in adverse effects caused by agrochemicals isolated or in binary combination, even though they are sharing genotoxicity damage induction as a common toxicity pathway. Conversely, some effects observed for isolated or binary combinations of agrochemicals were not observed for ternary combination, suggesting a chemical interaction that could imply antagonism character. Using a multivariate data analysis approach, exposure to isolated agrochemicals were related to a group of adverse effects characterized by hepatic lesion and the attempt of the tissue to mobilize defense cells and increase mitotic rates to minimize damages. Binary mixtures also share similarities in relation to the effects they exhibited, mainly a moderate to high increase in the GST activity and in histopathological alterations suggesting that binary combinations trigger an increased response of the mechanism of xenobiotics biotransformation. Together, obtained results bring important insights regarding adverse effects and possible interaction of the three agrochemicals whose residues are commonly detected in agro-food products.
Assuntos
Agroquímicos/toxicidade , Análise de Dados , Mediadores da Inflamação/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Maturidade Sexual/efeitos dos fármacos , Animais , Fígado/química , Masculino , Análise Multivariada , Ratos , Ratos Wistar , Maturidade Sexual/fisiologiaRESUMO
This study proposes an index for food labeling in order to promote sustainable consumption. The index is calculated by ranking multiple features from the environmental, health and nutritional dimensions of the target product in relation to a pre-set reference value; the obtained scores from each dimension are plotted in a radar chart resulting in a triangular area. An increase in area represents a greater impact. As examples, tuna and the potato-based foods at three different processing levels (in natura or minimally processed, processed and ultra-processed) were analyzed. For both cases, the index increases according to the processing grades and has proved to be capable of expressing in numbers and graphically a wide range of environmental, nutritional and health issues.
Assuntos
Dieta , Alimentos , Manipulação de Alimentos , Valor NutritivoRESUMO
For the first time, juvenile toxicity of inorganic arsenic (As) was investigated in male rats, focusing on reproductive effects. As is a metalloid naturally occurring in the environment, being the inorganic forms the most toxics. Contaminated drinking water and agricultural products are the main prospectors of intoxication for general population. In the present study, Wistar male rats (21 days old) were distributed into three groups (n = 10/group): control (received vehicle-filtered drinking water), As1 (received AsNaO2 at 0.01 mg L-1 ) and As2 (received AsNaO2 at 10 mg L-1 ). The animals were euthanized on PND 53. Testicular damages increased in As1 and As2 compared to control (ie, presence of vacuolization, acidophilic cells, and epithelium degeneration). Testicular interstitium of As1 and As2 presented fluid's increase and intense inflammatory infiltration. In the epididymis there was reduction of sperm amount in the lumen, besides epithelium areas presenting cribriform aspect in As1 and As2, exfoliation of cells in the light (in As1) and vacuoles (in As2). In epididymis interstitium, inflammatory infiltrates were observed in initial segment of As1 and As2. AsNaO2 changed immunolabeling pattern for androgen receptor in epididymis of As2, although serum testosterone levels was statistically comparable to control. Mass spectrometry revealed higher As concentrations in testis and epididymis of As2 compared to As1 and Control. These results indicate compromise of spermatogenesis and epididymal histophysiology in AsNaO2 -treated animals, possibly impairing sperm quality and fertility in long-term, even at low levels of exposure. Investigations about the reversibility of reproductive damages are necessary to better understand the mechanisms of As reproductive toxicity.
Assuntos
Arsenitos/toxicidade , Epididimo/efeitos dos fármacos , Epididimo/patologia , Maturidade Sexual/efeitos dos fármacos , Compostos de Sódio/toxicidade , Espermatogênese/efeitos dos fármacos , Animais , Intoxicação por Arsênico/patologia , Intoxicação por Arsênico/fisiopatologia , Arsenitos/farmacologia , Fertilidade/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar , Reprodução/efeitos dos fármacos , Compostos de Sódio/farmacologia , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testes de Toxicidade , Poluentes Químicos da Água/toxicidadeRESUMO
Prochloraz (PCZ) is a fungicide and androgen-receptor antagonist used worldwide in horticulture and agriculture. Pre- and perinatal exposure to this pesticide during sexual differentiation is deleterious for male offspring. Since data on the effects of PCZ on epididymal functions are scarce, and because sperm maturation occurs in this organ, the present investigation aimed to determine whether low PCZ doses administered to rats during the phase of sperm transit through the epididymis might affect the morphophysiology of this organ and sperm quality. Adult male Wistar rats were assigned to 4 different groups: 0 (control, vehicle) or 10, 15, or 30 mg/kg bw/d PCZ diluted in corn oil administered orally for 4 consecutive days. Morphofunctional parameters of the male reproductive tract, hormone concentrations, sperm evaluations, and fertility and histopathologic analysis of testis and epididymis were assessed. There were no statistically significant differences between treated and control groups in relation to all evaluated parameters. Data demonstrated show that PCZ exposure for a brief 4-d exposure and low doses did not produce reproductive toxicity or compromise sperm quality in adult rats.
Assuntos
Antagonistas de Androgênios/toxicidade , Epididimo/efeitos dos fármacos , Fertilidade/efeitos dos fármacos , Fungicidas Industriais/toxicidade , Imidazóis/toxicidade , Espermatogênese/efeitos dos fármacos , Testículo/efeitos dos fármacos , Administração Oral , Antagonistas de Androgênios/efeitos adversos , Animais , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Epididimo/citologia , Epididimo/crescimento & desenvolvimento , Feminino , Fungicidas Industriais/administração & dosagem , Humanos , Imidazóis/administração & dosagem , Inseminação Artificial , Masculino , Tamanho do Órgão/efeitos dos fármacos , Distribuição Aleatória , Ratos Wistar , Análise do Sêmen , Testículo/citologia , Testículo/crescimento & desenvolvimento , Testes de Toxicidade SubagudaRESUMO
The normal development of the male reproductive system can be divided into five phases: fetal, neonatal, childhood, puberty and adulthood. Childhood/peripuberty has yet been relatively little studied. Chemical insults during the peripubertal phase may result in adverse consequences that may be already visible during puberty as well as during later adult life. This occurs because endocrine disruptors often interfere in the developmental programming. The most important is to note that children are not just little adults and should be particularly investigated. The aim of this review is to discuss the recent literature (2000-2013) on male reproductive aspects in prepubertal toxicity assays, focusing on experimental in vivo studies, establishing a comparative analysis between the design, endpoints, results and consequent conclusion. The studies discussed in the present review were selected based on the period of exposure. Only studies with post-lactational exposures were included. 33 papers were included using rats, mice, rabbits or pigs as experimental model. There is a relative scarcity of studies investigating animals in development and thus an urgent need for further studies in order to evaluate the possible persistent effects on fertility and other reproductive parameters at adulthood. Another point is the lack of studies with chemical mixtures, an imminent problem in modern society. It is vital to consider the refinement of alternative methods and the experimental designs and endpoints to improve the scientific knowledge in this area.
Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Desenvolvimento Fetal/efeitos dos fármacos , Puberdade/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos , Animais , Criança , Desenvolvimento Infantil/fisiologia , Disruptores Endócrinos/efeitos adversos , Desenvolvimento Fetal/fisiologia , Humanos , Masculino , Puberdade/fisiologia , Reprodução/fisiologia , Maturidade Sexual/fisiologiaRESUMO
BACKGROUND: Smoking is the most relevant environmental factor that affects the development of aortic aneurysm. Smokers have elevated levels of elastase activity in the arterial wall, which leads to weakening of the aorta. The aim of this study was to verify whether cigarette smoke exposure itself is capable of altering the aortic wall. METHODS: Forty-eight Wistar rats were divided into 2-, 4-, and 6-month experimental periods and into 2 groups: smokers (submitted to smoke exposure at a rate of 40 cigarettes/day) and nonsmokers. At the end of the experimental periods, the aortas were removed and cross-sectioned to obtain histologic specimens for light microscopic and morphometric analyses. The remaining longitudinal segments were stretched to rupture and mechanical parameters were determined. RESULTS: A degenerative process (i.e., a reduction in elastic fibers, the loss of lamellar arrangement, and a reduction of smooth muscle cells) was observed, and this effect was proportional in intensity to the period of tobacco exposure. We observed a progressive reduction in the yield point of the thoracic aorta over time (P < 0.05). There was a decrease in stiffness (P < 0.05) and in failure load (P < 0.05) at 6 months in the abdominal aorta of rats in the smoking group. CONCLUSIONS: Chronic exposure to tobacco smoke can affect the mechanical properties of the aorta and can also provoke substantial structural changes of the arterial wall.
Assuntos
Aorta Abdominal/patologia , Aorta Torácica/patologia , Fumar/fisiopatologia , Poluição por Fumaça de Tabaco/efeitos adversos , Animais , Aorta Abdominal/fisiopatologia , Aorta Torácica/fisiopatologia , Modelos Animais de Doenças , Elasticidade , Masculino , Ratos , Ratos Wistar , Fumar/patologiaRESUMO
Recent studies indicate that several anomalies of the male reproductive system may be produced by acute or chronic exposure to chemical substances released into the environment, attributed to increased industrial development. Among these substances are trace metals such as cadmium (Cd). The aim of this study was to assess reproductive parameters in adult male rats whose mothers were exposed to Cd during pregnancy and lactation. For this, pregnant rats were divided into two experimental groups: treated rats, which received ad libitum cadmium acetate (CdAc) solution in distilled water (10 mg Cd/L), and control rats, which received sodium acetate (NaAc) solution in distilled water (equimolar to the CdAc). The results showed that the exposure to Cd in utero and through lactation adversely affected sperm quality of adult rats, as evidenced by compromised sperm morphology and motility and increased rate of cell death in testis.