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1.
Pharmacol Biochem Behav ; 197: 173000, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32702398

RESUMO

Psychostimulant drugs addiction is a chronic public health problem and individuals remain susceptible to relapses increasing public expenses even after withdrawal and treatment. Our research group has focused on finding new therapies to be employed in drug addiction treatment, suggesting the physical exercise as a promising tool. This way, it is necessary to know the mechanisms involved in the beneficial influences of physical exercise observing the pathway that could be explored in drug addiction treatment. Male Wistar rats were conditioned with amphetamine (AMPH) following the conditioned place preference (CPP) protocol and subsequently submitted to swimming for 5 weeks (1 h per day, 5 days per week). Half of the animals were injected with Naloxone (0.3 mg/mL/kg body weight, i.p.) 5 min prior each physical exercise day. After AMPH-CPP re-exposure, our outcomes showed that physical exercise, in addition to minimizing the relapse behavior in the CPP, it increased D1R, D2R and DAT in the Ventral Tegmental Area (VTA), but not in the Nucleus accumbens (NAc). Interestingly, while naloxone inhibited the partial beneficial influence of the exercise on drug-relapse behavior, exercise-induced changes in the dopaminergic system were not observed in the group administered with naloxone as well. Based on these evidences, besides reinforcing the beneficial influence of the physical exercise on AMPH-induced drug addiction, we propose the involvement of endogenous opioid system activation, not as a single one, but as a possible mechanism of action resulting from the physical activity practice, thus characterizing an important therapeutic approach, which may contribute to drug withdrawal consequently preventing relapse.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/terapia , Anfetamina/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Condicionamento Físico Animal/métodos , Animais , Condicionamento Clássico/efeitos dos fármacos , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Locomoção/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Núcleo Accumbens/metabolismo , Ratos , Ratos Wistar , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Natação , Área Tegmentar Ventral/metabolismo
2.
Eur Neuropsychopharmacol ; 32: 25-35, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31899030

RESUMO

Addiction is a devastating worldwide disorder that requires effective and innovative therapies. Physical exercise could be useful in addiction treatment because it shares a common neural circuit with addictive drugs. Based on this, molecular adaptations consequent to time of exercise in opioid exposed animals were evaluated. Rats were designed as sedentary (SED) or exercised (EXE). This last group was separated to perform three different periods of swimming: short-term (S-EXE), medium-term (M-EXE) and long-term (L-EXE) for 14, 28 and 42 days, respectively. On the last exercising week, one-half of the animals from SED and all animals from S-, M- and l-EXE were concomitantly exposed to morphine-conditioned place preference (CPP) paradigm and y-maze task for behavioral assessments followed by molecular assays in both Nucleus accumbens (NAc) and hippocampus. Between SED groups, morphine conditioning showed drug-CPP and increased dopamine transporter (DAT), dopamine receptor type-1 (D1R), type-2 (D2R) and glucocorticoid receptor (GR) in both brain areas in relation to saline group. Besides the small morphine-CPP in relation to SED group, all periods decreased DAT, D1R, and GR immunoreactivity in NAc, DAT and D1R in hippocampus, while D2R in both brain areas and GR in hippocampus were primarily decreased by L-EXE. Our findings show that even a short-term exercise modifies behaviors related to drug withdrawal, changing DA targets and GR, which are closely linked to addiction. Therefore, our outcomes involving physical exercise are interesting to perform a possible clinical trial, thus expanding the knowledge about drug addiction.


Assuntos
Condicionamento Psicológico/fisiologia , Transtornos Relacionados ao Uso de Opioides/metabolismo , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Condicionamento Físico Animal/fisiologia , Comportamento Sedentário , Animais , Condicionamento Psicológico/efeitos dos fármacos , Masculino , Morfina/administração & dosagem , Condicionamento Físico Animal/psicologia , Condicionamento Físico Animal/tendências , Ratos , Ratos Wistar , Natação/fisiologia , Natação/psicologia , Natação/tendências , Fatores de Tempo
3.
Neurosci Lett ; 714: 134560, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31622649

RESUMO

INTRODUCTION: Ketamine (KET) is an anesthetic agent widely used in human and veterinary medicine. According to studies, KET is associated to direct neutorotoxic damages due to its capacity to induce oxidative stress. Because of the free radical generation in the organism and its relation with diseases' development, there is a growing interest to study antioxidant molecules, such as gallic acid (GA), a natural phenolic compound. AIM: Evaluate the GA antioxidant potential for the prevention of oxidative damage in the brain and liver tissue of rats exposed to acute KET administration. MATERIAL AND METHODS: 32 Wistar male rats received GA (by gavage, 13.5 mg/kg) for three consecutive days, 24 h after the last GA dose, animals were anesthetized with KET (50 mg/kg, i.m.). All animals were euthanized by decapitation 60 min after KET administration. The liver, brain cortex and hippocampus were removed and homogenized for biochemical analysis. RESULTS: In brain cortex, KET increased reactive species (RS) generation, protein carbonyls (PC) levels and reduced non-protein thiols (NPSH) levels, while GA pre-treatment reduced PC and increased NPSH levels. KET increased PC and decreased NPSH levels in the hippocampus, and GA reduced PC and NPSH levels. In the liver, no difference was observed in the RS generation, while KET induced and increase of PC levels and decreased NPSH levels, while GA pre-treatment prevented it. CONCLUSION: GA administration can prevent oxidative damage caused by acute KET administration and minimize its noxious effects. Further studies are needed to evidence GA antioxidant properties regarding KET chronic use.


Assuntos
Anestésicos Dissociativos/toxicidade , Córtex Cerebral/efeitos dos fármacos , Ácido Gálico/farmacologia , Hipocampo/efeitos dos fármacos , Ketamina/toxicidade , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Córtex Cerebral/metabolismo , Hipocampo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Masculino , Carbonilação Proteica/efeitos dos fármacos , Ratos , Ratos Wistar , Compostos de Sulfidrila/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
4.
Brain Res Bull ; 135: 69-76, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28964775

RESUMO

Amphetamine (AMPH) and its derivatives are addictive drugs used to promote and enhance alertness, motivation, willingness, courage and wellbeing. However, their chronic use is related to memory loss, emotional instability, insomnia, psychosis and paranoia. In the last decades, modern society has included processed foods, rich in trans fatty acids (TFA), in their diet, what has been related to several health problems including increased AMPH preference and self-administration. In this scenario, physical activity appears to be useful to attenuate rewarding symptoms related to addictive drugs mainly by affecting brain neuroplasticity and neurotransmission. The current study has been developed to assess the influence of physical activity on addiction parameters of rats exposed to AMPH which were previously supplemented with hydrogenated vegetable fat (HVF), rich in TFA. After six weeks of HVF or soybean oil (SO, control group) supplementation, adult rats were conditioned with d,l-AMPH or vehicle for 14 days. Then, half of each experimental group was submitted to physical activity in treadmill running sessions (60min/day, 5 days/week) for 5 weeks. Animals were re-conditioned with AMPH or vehicle for 3 more days, to observe drug relapse. Locomotor activity and anxiety-like symptoms were observed 24h after the last AMPH reconditioning, and fatty acids composition was quantified in the ventral tegmental area, striatum and prefrontal cortex. All animals showed AMPH preference, but only SO sedentary showed drug relapse. No differences were observed in locomotor activity among groups, while HVF-supplemented group showed decreased exploration per se, and physical activity prevented this. Moreover, AMPH-HVF group showed increased anxiety-like symptoms, which were prevented by physical activity. These results indicate that HVF supplementation modifies AMPH addiction, whereas regular physical activity could be protective against both AMPH and TFA damages.


Assuntos
Ansiedade/fisiopatologia , Condicionamento Físico Animal/psicologia , Ácidos Graxos trans/uso terapêutico , Anfetamina/metabolismo , Anfetamina/farmacologia , Transtornos Relacionados ao Uso de Anfetaminas/fisiopatologia , Transtornos Relacionados ao Uso de Anfetaminas/terapia , Animais , Ansiedade/metabolismo , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Córtex Cerebral/metabolismo , Hipocampo/metabolismo , Masculino , Atividade Motora , Condicionamento Físico Animal/métodos , Condicionamento Físico Animal/fisiologia , Ratos , Ratos Wistar , Óleo de Soja/metabolismo , Ácidos Graxos trans/metabolismo , Verduras
5.
Artigo em Inglês | MEDLINE | ID: mdl-26555614

RESUMO

Amphetamine (AMPH) abuse is a world concern and a serious public health problem. Repeated administration of high doses of AMPH induces neuropsychiatric consequences, including addiction, reward and psychosis, whose pharmacological treatment has shown limited effectiveness. The m-trifluoromethyl-diphenyldiselenide [(m-CF3-PhSe)2] has been documented as a promising pharmacological agent in different animal models related to oxidative damage. In this study, we examined the influence of (m-CF3-PhSe)2 on withdrawal following re-exposure to AMPH. Wistar rats received d,l-AMPH or saline in the conditioned place preference (CPP) paradigm for 8days. Then, half of each initial (AMPH or saline) experimental group was treated with (m-CF3-PhSe)2 or vehicle, resulting in four final groups: i) Saline/vehicle; ii) (m-CF3-PhSe)2/saline; iii) AMPH/vehicle; and iv) AMPH/(m-CF3-PhSe)2. After fourteen days of (m-CF3-PhSe)2 treatment, animals were re-exposed to AMPH or vehicle in the CPP paradigm for three more days in order to assess drug re-conditioning and memory/locomotor activity, performed 24h after AMPH re-exposure in the CPP and the Y maze, respectively. Subsequently, ex-vivo assays were carried out in samples of the prefrontal cortex (PFC) of the animals. The (m-CF3-PhSe)2 treatment was able to prevent AMPH-induced re-conditioning symptoms in rats. Behavioral observations in the Y maze task showed no significant changes. AMPH exposure was able to increase 5-HT uptake as well as oxidative damage in the PFC, whereas (m-CF3-PhSe)2 treatment exerted a preventative effect against these alterations. The current findings suggest that (m-CF3-PhSe)2 might be considered a promising therapeutic tool for AMPH-induced addiction.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Anfetamina/farmacologia , Atividade Motora/efeitos dos fármacos , Compostos de Organossilício/farmacologia , Síndrome de Abstinência a Substâncias , Animais , Aprendizagem por Associação/efeitos dos fármacos , Comportamento de Escolha/efeitos dos fármacos , Condicionamento Operante/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Ratos , Ratos Wistar
6.
Food Chem Toxicol ; 69: 38-45, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24694906

RESUMO

We evaluated the influence of dietary fats on ultraviolet radiation (UVR)-induced oxidative damage in skin of rats. Animals from two consecutive generations born of dams supplemented with fats during pregnancy and breastfeeding were maintained in the same supplementation: soybean-oil (SO, rich in n-6 FA, control group), fish-oil (FO, rich in n-3 FA) or hydrogenated-vegetable-fat (HVF, rich in TFA). At 90 days of age, half the animals from the 2nd generation were exposed to UVR (0.25 J/cm(2)) 3×/week for 12 weeks. The FO group presented higher incorporation of n-3 FA in dorsal skin, while the HVF group incorporated TFA. Biochemical changes per se were observed in skin of the HVF group: greater generation of reactive oxygen species (ROS), lower mitochondrial integrity and increased Na(+)K(+)-ATPase activity. UVR exposure increased skin wrinkles scores and ROS generation and decreased mitochondrial integrity and reduced-glutathione levels in the HVF group. In FO, UVR exposure was associated with smaller skin thickness and reduced levels of protein-carbonyl, together with increased catalase activity and preserved Na(+)K(+)-ATPase function. In conclusion, while FO may be protective, trans fat may be harmful to skin health by making it more vulnerable to UVR injury and thus more prone to develop photoaging and skin cancer.


Assuntos
Óleos de Peixe/farmacologia , Pele/efeitos da radiação , Ácidos Graxos trans/farmacologia , Raios Ultravioleta/efeitos adversos , Animais , Antioxidantes/metabolismo , Gorduras na Dieta/farmacologia , Ácidos Graxos/análise , Feminino , Hidrogenação , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/efeitos da radiação , Gravidez , Carbonilação Proteica/efeitos dos fármacos , Carbonilação Proteica/efeitos da radiação , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Óleo de Soja/farmacologia , Luz Solar/efeitos adversos
7.
Behav Brain Res ; 262: 94-100, 2014 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-24445072

RESUMO

Exercise has been reported to attenuate rewarding symptoms related to addictive drugs mainly by affecting the brain neuroplasticity and neurotransmission. In this study, we investigated the influence of physical exercise on the behavioral and enzymatic status related to drug relapse in rats. Animals were primarily treated with amphetamine (AMPH; 4.0 mg/kg, i.p.) or vehicle (C; NaCl 0.9% solution) in the conditioned place preference (CPP) paradigm for 14 days. Half of each experimental group was then submitted to swimming sessions (60 min/day, 5 days/week) for 5 weeks. Animals were re-exposed to AMPH- or vehicle-CPP paradigm for another 3 days, in order to observe drug relapse and anxiety-like symptoms, which were observed 24h after AMPH reconditioning in CPP, and elevated plus maze (EPM), respectively, and brain biochemical evaluations were carried out subsequently. While AMPH was related to place preference and anxiety, indicating drug addiction and abstinence symptoms, respectively, physical activity was able to prevent relapse symptoms after AMPH reconditioning, as observed through consecutive decreased CPP and anxiety-like symptoms. In addition, AMPH exposure increased reactive species (RS) generation and protein carbonyl (PC) levels together with decreased activity of catalase- and Na(+)K(+)-ATPase in hippocampus. On the other hand, while all AMPH-induced effects were prevented by physical activity, there was a negative correlation between PC levels (r=0.65; p<0.003) and CAT activity, and a positive correlation between RS generation and PC levels (r=0.54; r=0.52, p<0.05) with AMPH-CPP after exercise. These results indicate that exercise has a clear beneficial influence on the prevention of psychostimulant drug relapse.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Condicionamento Físico Animal , Anfetamina/administração & dosagem , Animais , Ansiedade , Biomarcadores/metabolismo , Catalase/metabolismo , Condicionamento Psicológico , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Ratos , Ratos Wistar , Prevenção Secundária , ATPase Trocadora de Sódio-Potássio/metabolismo
8.
Lipids ; 48(10): 977-87, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23737082

RESUMO

We evaluated the influence of fish oil (FO, rich in n-3 FA), soybean oil (SO, rich in n-6 FA) and hydrogenated vegetable fat (HVF, rich in trans FA) on the oxidative status and viability of skin cells of mice exposed to ultraviolet radiation (UVR). Mice were supplemented with FO, SO or HVF for three months and exposed to UVR (2.72 mJ/cm(2)) for 2 days. One day after the last UVR session, the FO group showed higher levels of n-3 fatty acids (FA), while the HVF showed higher incorporation of trans FA (TFA) in dorsal skin. UVR increased lipid peroxidation and protein carbonyl levels of the HVF and to a lesser extent of the control and SO groups. Although all irradiated groups showed increased skin thickness, this increase was slighter in FO mice. UVR exposure reduced skin cell viability of the control, SO and HVF groups, while FO prevented this. Catalase activity was reduced independently of the supplementation and SOD level was increased in C and FO groups after UVR exposure; FO prevented the UVR-induced increase in glutathione levels, which was observed in skin of the control, SO and HVF mice. Our results showed the beneficial effects of FO supplementation, as well as the harmful effects of trans FA, whose intensity can increase vulnerability to skin diseases.


Assuntos
Dieta , Estresse Oxidativo/efeitos dos fármacos , Pele/efeitos dos fármacos , Ácidos Graxos trans/farmacologia , Raios Ultravioleta , Análise de Variância , Animais , Sobrevivência Celular/efeitos dos fármacos , Óleos de Peixe/farmacologia , Masculino , Camundongos , Estresse Oxidativo/efeitos da radiação , Pele/efeitos da radiação , Óleo de Soja/farmacologia
9.
Ecotoxicol Environ Saf ; 91: 103-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23433555

RESUMO

The aim of this study was to compare the effects of manganese (Mn) on silver catfish exposed to different levels of dissolved oxygen. Silver catfish (Rhamdia quelen) were exposed to increasing concentrations of Mn (4.2, 8.4 or 16.2mgL(-1)) under either normoxia (100 percent saturation) or moderate hypoxia (51.87 percent saturation) for 15 days. Under normoxia, Mn exposure increased lipid peroxidation (LP) in brain and kidney; it increased gluthatione (GSH) levels in brain and decreased catalase (CAT) activity in both tissues. Moderate hypoxia was able to prevent Mn-induced LP in brain and to reduce this oxidative parameter in kidney; GSH level was increased in brain, while CAT activity was reduced in both tissues. Activity of isolated mitochondria of liver and gills was reduced by Mn exposure under both levels of dissolved oxygen, but this effect was more prominent in normoxia. As expected, liver, kidney and gills showed an increase of Mn accumulation according to waterborne levels, and these parameters presented positive relationship. The highest waterborne Mn (8.4 and 16.2mgL(-1)) resulted in greater accumulation under normoxia, indicating that moderate hypoxia can stimulate mechanisms capable of reducing Mn accumulation in tissues (though not in blood). Moderate hypoxia can be considered a stress factor and Mn an aquatic anthropogenic contaminant. Therefore we hypothesized that these two conditions together are able to invoke defense mechanisms in juvenile silver catfish, acting in a compensatory form, which may be related to adaptation and/or hormesis.


Assuntos
Peixes-Gato/fisiologia , Peroxidação de Lipídeos/efeitos dos fármacos , Manganês/toxicidade , Oxigênio/farmacologia , Poluentes Químicos da Água/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Peixes-Gato/metabolismo , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Manganês/análise , Manganês/metabolismo , Mitocôndrias/efeitos dos fármacos , Poluentes Químicos da Água/análise
10.
Behav Brain Res ; 226(2): 504-10, 2012 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-22004982

RESUMO

The influence of trans fatty acids (FA) on development of orofacial dyskinesia (OD) and locomotor activity was evaluated. Rats were fed with diets enriched with 20% soybean oil (SO; n-6 FA), lard (L; saturated FA) or hydrogenated vegetable fat (HVF; trans FA) for 60 weeks. In the last 12 weeks each group was subdivided into sedentary and exercised (swimming). Brains of HVF and L-fed rats incorporated 0.33% and 0.20% of trans FA, respectively, while SO-fed group showed no incorporation of trans FA. HVF increased OD, while exercise exacerbated this in L and HVF-fed rats. HVF and L reduced locomotor activity, and exercise did not modify. Striatal catalase activity was reduced by L and HVF, but exercise increased its activity in the HVF-fed group. Na(+)K(+)-ATPase activity was not modified by dietary FA, however it was increased by exercise in striatum of SO and L-fed rats. We hypothesized that movement disorders elicited by HVF and less by L could be related to increased dopamine levels in striatum, which have been related to chronic trans FA intake. Exercise increased OD possibly by increase of brain dopamine levels, which generates pro-oxidant metabolites. Thus, a long-term intake of trans FA caused a small but significant brain incorporation of trans FA, which favored development of movement disorders. Exercise worsened behavioral outcomes of HVF and L-fed rats and increased Na(+)K(+)-ATPase activity of L and SO-fed rats, indicating its benefits. HVF blunted beneficial effects of exercise, indicating a critical role of trans FA in brain neurochemistry.


Assuntos
Catalase/metabolismo , Corpo Estriado/enzimologia , Gorduras na Dieta/efeitos adversos , Discinesia Induzida por Medicamentos/metabolismo , Condicionamento Físico Animal/fisiologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Ácidos Graxos trans/efeitos adversos , Animais , Masculino , Atividade Motora/efeitos dos fármacos , Condicionamento Físico Animal/métodos , Ratos , Ratos Wistar , Ácidos Graxos trans/metabolismo
11.
Neuroscience ; 195: 80-8, 2011 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-21893165

RESUMO

Here we evaluated the influence of physical exercise on behavior parameters and enzymatic status of rats supplemented with different dietary fatty acids (FA). Male Wistar rats fed diets enriched with soybean oil (SO), lard (L), or hydrogenated vegetable fat (HVF) for 48 weeks were submitted to swimming (30 min/d, five times per week) for 90 days. Dietary FA per se did not cause anxiety-like symptoms in the animals, but after physical exercise, SO group showed a better behavioral performance than L and the HVF groups in elevated plus maze (EPM). In Barnes maze, HVF group showed impaired memory acquisition as compared to L group, and exercise reversed this effect. SO-fed rats showed an improvement in memory acquisition after 1 day of training, whereas lard caused an improvement of memory only from day 4. HVF-fed rats showed no improvement of memory acquisition, but this effect was reversed by exercise in all training days. A lower activity of the Na(+)K(+)-ATPase in brain cortex of rats fed lard and HVF was observed, and this effect was maintained after exercise. Similarly, the HVF diet was related to lower activity of hippocampal Na(+)K(+)-ATPase, and exercise reduced activity of this enzyme in the SO and L groups. Our findings show influences of dietary FA on memory acquisition, whereas regular exercise improved this function and was beneficial on anxiety-like symptoms. As FA are present in neuronal membrane phospholipids and play a critical role in brain function, our results suggest that low incorporation of trans FA in neuronal membranes may act on cortical and hippocampal Na(+)K(+)-ATPase activity, but this change appears to be unrelated to the behavioral parameters primarily harmed by consumption of trans and less so by saturated FA, which were reversed by exercise.


Assuntos
Encéfalo/metabolismo , Gorduras na Dieta/efeitos adversos , Memória/fisiologia , Condicionamento Físico Animal/fisiologia , Animais , Ansiedade/metabolismo , Masculino , Aprendizagem em Labirinto/fisiologia , Óleos de Plantas/efeitos adversos , Ratos , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/metabolismo , Óleo de Soja/efeitos adversos
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