RESUMO
We developed a model for evaluating the environmental risk of persistent organic pollutants (POPs) to aquatic organisms. The model is based on fuzzy theory and uses information provided by international experts through a questionnaire. It has been tested in two case studies for a particular type of POPs: brominated flame retardants (BFRs). The first case study is related to the EU-funded AQUATERRA project, with sampling campaigns carried out in two Ebro tributaries in Spain (the Cinca and Vero Rivers). The second one, named the BROMACUA project, assessed different aquatic ecosystems in Chile (San Vicente Bay) and Colombia (Santa Marta Marsh). In both projects, the BFRs under study were polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCD). However, the model can be extrapolated to other POPs and to different aquatic ecosystems to provide useful results for decision-makers.
Assuntos
Monitoramento Ambiental/métodos , Modelos Químicos , Poluentes Químicos da Água/análise , Poluição Química da Água/estatística & dados numéricos , Chile , Colômbia , Ecossistema , Retardadores de Chama/análise , Lógica Fuzzy , Éteres Difenil Halogenados/análise , Hidrocarbonetos Bromados/análise , Medição de Risco/métodos , EspanhaRESUMO
Environmental chemicals may be involved in the etiology of breast cancers. Many studies have addressed the association between cancer in humans and agricultural pesticide exposure. Organophosphorous pesticides have been used extensively to control mosquito plagues. Parathion and malathion are organophosphorous pesticides extensively used to control a wide range of sucking and chewing pests of field crops, fruits, and vegetables. They have many structural similarities with naturally occurring compounds, and their primary target of action in insects is the nervous system; they inhibit the release of the enzyme acetylcholinesterase at the synaptic junction. Eserine, parathion, and malathion are cholinesterase inhibitors responsible for the hydrolysis of body choline esters, including acetylcholine at cholinergic synapses. Atropine, a parasympatholytic alkaloid, is used as an antidote to acetylcholinesterase inhibitors. The aim of this study was to examine whether pesticides were able to induce malignant transformation of the rat mammary gland and to determine whether alterations induced by these substances increase the cholinergic activation influencing such transformation. These results showed that eserine, parathion, and malathion increased cell proliferation of terminal end buds of the 44-day-old mammary gland of rats, followed by formation of 8.6, 14.3, and 24.3% of mammary carcinomas, respectively, after about 28 months. At the same time, acetylcholinesterase activity decreased in the serum of these animals from 9.78 +/- 0.78 U/mL in the control animals to 3.05 +/- 0.06 U/mL; 2.57 +/- 0.15 U/mL; and 3.88 +/- 0.44 U/mL in the eserine-, parathion-, and malathion-treated groups, respectively. However, atropine alone induced a significant (p < 0.05) decrease in the acetylcholinesterase activity from the control value of 9.78 +/- 0.78 to 4.38 +/- 0.10 for atropine alone, to 1.32 +/- 0.06 for atropine in combination with eserine, and 2.39 +/- 0.29 for atropine with malathion, and there was no mammary tumor formation. These results indicate that organophosphorous pesticides induce changes in the epithelium of mammary gland influencing the process of carcinogenesis, and such alterations occur at the level of nervous system by increasing the cholinergic stimulation.
Assuntos
Acetilcolinesterase/efeitos dos fármacos , Inibidores da Colinesterase/toxicidade , Inseticidas/toxicidade , Malation/toxicidade , Glândulas Mamárias Animais/efeitos dos fármacos , Neoplasias Mamárias Experimentais/induzido quimicamente , Paration/toxicidade , Fisostigmina/toxicidade , Acetilcolinesterase/metabolismo , Animais , Atropina/farmacologia , Divisão Celular , Transformação Celular Neoplásica/induzido quimicamente , Feminino , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/patologia , Neoplasias Mamárias Experimentais/patologia , Parassimpatolíticos/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
It has been shown that oral administration of melatonin to Suffolk ewe lambs, from 10 weeks of age onwards, advances the onset of puberty compared with control lambs maintained under the same natural photoperiod. Luteinizing hormone (LH) pulse frequency at 20 and 26 weeks of age was unchanged by melatonin. However, LH pulse amplitudes greater than 1 ng mL(-1) were consistently observed in melatonin-treated lambs, suggesting either a high responsiveness of the pituitary gland to endogenous gonadotrophin-releasing hormone (GnRH) pulses, or a large amount of GnRH released by each pulse. The purpose of the present study was to assess the pituitary responsiveness to six diurnal and six nocturnal exogenous pulses of GnRH (10 ng kg(-1) bodyweight) in melatonin-treated ewe lambs (3 mg melatonin daily at 1600 hours, from 10 weeks of age; n = 5) and control lambs of the same age (n = 5), born in the spring and kept under natural photoperiod. Pulses of GnRH were given intravenously at 60-min intervals by means of an indwelling jugular catheter from 0900 to 1400 hours and from 2100 to 0200 hours to ewe lambs of 20 and 26 weeks of age. Blood samples were collected at 10-min intervals using a contralateral jugular vein catheter from 1 h before and up to 1 h after the last GnRH pulse. The difference (delta) between plasma LH concentrations at 0 min and the greatest concentration of LH after each GnRH pulse was calculated and compared in the same group. The total area under the GnRH response curve (AUC) was also calculated and compared within and between the groups. The AUC of melatonin-treated lambs (66.1 +/- 5.94 and 52.24 +/- 7.42 ng mL(-1)/6 h, diurnal and nocturnal respectively) was greater than that of control lambs (39.42 +/- 4.29 and 32.82 +/- 3.6 ng mL(-1)/6 h diurnal and nocturnal respectively; P<0.05) at 20 weeks of age. At 26 weeks of age, only the diurnal total AUC was greater in melatonin-treated lambs than in control lambs (60.17 +/- 7.98 and 29.8 +/- 5.02 ng mL(-1)/6 h respectively; P<0.05). Delta LH concentrations in response to the first diurnal pulse of GnRH were greater than those in response to the fifth diurnal GnRH pulse (P<0.05) in melatonin-treated lambs of 20 weeks of age. Also, the delta LH concentrations in response to the first three diurnal GnRH pulses were greater than to the last three nocturnal pulses of GnRH (P<0.05). Delta LH concentrations were greater in response to the second diurnal pulse of GnRH than to the last three diurnal GnRH pulses, and greater than the responses to the first and the last four nocturnal GnRH pulses (P<0.05), at 26 weeks of age in melatonin-treated lambs. The response to nocturnal pulses of GnRH was similar. In control lambs, the responses to diurnal and nocturnal GnRH pulses were similar at 20 and 26 weeks of age. These results suggest that melatonin enhances the pituitary responsiveness to GnRH pulses in ewe lambs.
Assuntos
Ritmo Circadiano , Hormônio Liberador de Gonadotropina/administração & dosagem , Melatonina/farmacologia , Hipófise/efeitos dos fármacos , Hipófise/fisiologia , Ovinos/fisiologia , Envelhecimento , Animais , Feminino , Hormônio Luteinizante/sangue , Periodicidade , Maturidade Sexual/efeitos dos fármacos , Ovinos/crescimento & desenvolvimentoRESUMO
Smooth muscle myometrial cells isolated by an enzymatic method from estrogenized rats were used after 7-10 days of culture. They were incubated for 24 h with two distinct competitive nitric oxide (NO) inhibitors: NG-monomethyl-L-arginine (L-NMMA: 300 microM) and L-nitro-arginine methylester (L-NAME: 600 microM, 5 mM and 10 mM). Afterwards, the supernatants were separated in order to measure nitrite production and prostaglandin PGE synthesis. In the present report, we demonstrate that myometrial cells from estrogenized rats are able to produce NO, since all the inhibitors significantly decrease the production of nitrites in the culture media. Furthermore, we report that both inhibitors inhibited PGE synthesis by myometrial cells. We also used a donor of NO in the incubation medium for 24 h, sodium nitroprusside (NP), obtaining an strong (P< 0.001) increase in both nitrite and PGE production. We conclude that myometrial cells can produce NO and that one possible role of the NO synthetized by this cells may be the modulation of PGE production.
Assuntos
Músculo Liso/metabolismo , Miométrio/metabolismo , Óxido Nítrico/farmacologia , Prostaglandinas/biossíntese , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Estradiol/farmacologia , Feminino , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/biossíntese , Nitritos/análise , Prostaglandinas/análise , Ratos , Ratos Wistar , ômega-N-Metilarginina/farmacologiaRESUMO
Previously, we demonstrated the presence of a nitric oxide (NO) prostaglandin (PG) pathway in myometrial cells obtained from uterine rat tissue. This pathway was modulated by estrogen and one possible function could be to modulate uterine relaxation. In the present study, we investigated the role of progesterone in the regulation of NO synthesis and the uterotonic PGE production by myometrial cells from uterine rat tissue. We worked with two groups of rats: (i) ovariectomizcd (OV) rats, without influence of sex hormones and (ii) OV rats injected with progesterone (4 mg) s.c. Myometrial uterine cells were obtained by a selective enzymatic digestion. In the incubation medium of these cells, nitrite concentration (as a measure of NO production) and PGE production were evaluated. To ensure a specific response, a competitive NOs inhibitor, N(G)-monomethyl-L-arginine; L-NMMA (300 microM) was used. We found that at 48 h of the incubation period, cells obtained from progesterone-primed uterine tissue presented an increase in the nitrite concentration concomitant with a decrease in the PGE production. When L-NMMA was added to the cells, nitrite production and PGE synthesis returned to control values. The fact that this effect had not been observed in the group of cells obtained from OV rats suggests that progesterone was responsible for it. These data provide strong evidence that in spite of the fact that estrogen and progesterone modulate the NO-PG pathway in the uterine rat tissue, the two hormones have opposite effects.