Frederico Ferreira - Academia.edu (original) (raw)

Papers by Frederico Ferreira

Bioscience Journal, Jul 20, 2006

Feed restriction (FR) has been recognized as the major experimental assay able to retard aging an... more Feed restriction (FR) has been recognized as the major experimental assay able to retard aging and degeneration diseases, although the effects of dietary manipulation at Central Nervous System (CNS) superior functions as learning and memory remain controversial. The aim of the present study was to evaluate the FR effects in CNS superior functions focusing in learning and memory in rodent models. Male Wistar rats were divided into three groups (n = 9/group) according to dietary conditions: ad libitum (AL) with unlimited access to standard rat diet (22% of protein, 8% fiber, 4% fat, 10% minerals, 1.4% Calcium, 0.8% Phosphorus); FR30 and FR60 groups were fed with 70% and 40%, respectively, of total rat diet offered to the AL group for 15 weeks. The animals FR30 and FR60 showed significant increase of learning performance in Y maze compared to animals fed ad libitum. The FR30 group, in memory task, also showed strong preference to the correct arm in Y maze at the first trials and greater rightness probability, in relation to the AL and FR60 groups. The AL group had significantly higher exploratory activity at the open field test than both FR groups. These findings implicate the FR on modulation of CNS functions as learning, suggesting, also, a possible anxiogenic-like effect of stress caused by FR.

Rbm Rev Bras Med, Oct 1, 2009

Doutorando em Farmacologia da Universidade de São Paulo (USP) - Ribeirão Preto. ... Endocrinologi... more Doutorando em Farmacologia da Universidade de São Paulo (USP) - Ribeirão Preto. ... Endocrinologista. Professor assistente da Universidade Federal de Uberlândia. ... Professora titular da Disciplina de Fisiologia da Universidade Presidente Antônio Carlos, Araguari.

Bioscience Journal, Jun 19, 2007

As crescentes necessidades nutricionais da população exigem o desenvolvimento de mecanismos para ... more As crescentes necessidades nutricionais da população exigem o desenvolvimento de mecanismos para o aumento do valor nutricional na dieta. Uma alternativa é a complementação com diferentes fontes protéicas, sendo a combinação de arroz, feijão e castanha-do-pará uma possibilidade. O presente estudo analisou o efeito da adição da castanha-do-pará sobre o ganho de peso de animais e também observou o ritmo de absorção intestinal do óleo extraído da castanha-do-pará. Os experimentos foram conduzidos em conformidade com o guia de manipulação de animal de laboratório da Sociedade Brasileira de Biologia Experimental e normas do Comitê Internacional de Manipulação e Cuidados de Animais Experimentais. Utilizou-se 36 camundongos da linhagem albino suíço e 10 ratos da linhagem Wistar. O protocolo alimentício seguiu a dieta ideal proposta por Souza e Oliveira (1969). Camundongos alimentados com uma mistura de 3 partes de arroz e 1 de feijão acrescido 3,33%, 6,67% e 16,65% de castanha-do-pará apresentaram, ao final de duas semanas, significativamente maior ganho de peso médio, 20,43%, em relação aos camundongos alimentados com 0%, 33,3% e 50% de castanha-do-pará. A dieta acrescida em 16,65% de castanha-do-Pará aumentou de 40,74% o ganho de peso comparado ao controle. O teste de absorção intestinal não mostrou diferença significativa na taxa de absorção. O maior ganho de peso entre animais que receberam dieta enriquecida com castanha-do-Pará relaciona-se, entre outros fatores, com a maior biodisponibilidade do aminoácido metionina. Contudo, o acréscimo de maiores quantidades de castanha-do-Pará não revelou aumento no peso dos animais.

Toxicology Letters

A high-fat (HF) diet, the serotonergic system and stromal elements have all been implicated in co... more A high-fat (HF) diet, the serotonergic system and stromal elements have all been implicated in colon carcinogenesis. We investigated whether the colonic serotonergic system could play a main role in the development of colonic dysplasia and stromal reactivity in carcinogen-treated rats under HF diet. For this, dimethylhydrazine-treated rats were fed with standard diet and a HF diet. Fat distribution was quantified by computerized tomography exam, serotonergic activity was analyzed by high-performance liquid chromatography, gene expression, and immunohistochemistry, which along with histopathological technique enabled us to enumerate dysplasia, microvessels density, cell proliferation and COX-2 expression. We found that the HF diet induced an increase in the amount of visceral adipose tissue, even without expressive changes in the average body weight. This was correlated with a loss of serotonergic balance in colon tissue. Moreover, the HF diet promoted dysplasia and microvessel densi...

Genes Brain and Behavior

Nitric oxide (NO) is an atypical neurotransmitter that has been related to the pathophysiology of... more Nitric oxide (NO) is an atypical neurotransmitter that has been related to the pathophysiology of major depression disorder. Increased plasma NO levels have been reported in depressed and suicidal patients. Inhibition of neuronial nitric oxide synthase (nNOS), on the other hand, induces antidepressant effects in clinical and pre-clinical trials. The mechanisms responsible for the antidepressant-like effects of nNOS inhibitors, however, are not completely understood. In this study, genomic and proteomic analyses were used to investigate the effects of the preferential nNOS inhibitor 7-nitroindazole (7-NI) on changes in global gene and protein expression in the hippocampus of rats submitted to forced swimming test (FST). Chronic treatment (14 days, i.p.) with imipramine (15 mg/kg daily) or 7-NI (60 mg/kg daily) significantly reduced immobility in the FST. Saturation curves for Serial analysis of gene expression libraries showed that the hippocampus of animals submitted to FST presente...

Journal of Psychopharmacology

Systemic or intra-striatal acute administration of nitric oxide synthase (NOS) inhibitors causes ... more Systemic or intra-striatal acute administration of nitric oxide synthase (NOS) inhibitors causes catalepsy in rodents. This effect disappears after sub-chronic treatment. The aim of the present study was to investigate if this tolerance is related to changes in the expression of NOS or dopamine-2 (D2) receptor or to a recovery of NOS activity. Male albino Swiss mice (25-30 g) received single or sub-chronic (once a day for 4 days) i.p. injections of saline or L-nitro-arginine (L-NOARG, 40 mg/kg), a non-selective inhibitor of neuronal nitric oxide synthase (nNOS). Twenty-four hours after the last injection, the animals were killed and their brains were removed for immunohistochemistry assay to detect the presence of nNOS or for 'in-situ' hybridisation study using (35)S-labeled oligonucleotide probe complementary to D2 receptor mRNA. The results were analysed by computerised densitometry. Independent groups of animals received the same treatment, but were submitted to the catal...

FEMS Immunology & Medical Microbiology

Controversies over the vitamin D receptor (VDR) acting as a susceptibility factor in Mycobacteriu... more Controversies over the vitamin D receptor (VDR) acting as a susceptibility factor in Mycobacterium sp. infections may be the result of incorrect population stratification. The risk of leprosy occurrence conditioned by VDR polymorphism was investigated by stratifying the population of a highly endemic Brazilian region into negative and positive Mitsuda responses. Leprosy patients (102) and a group of healthy nonconsanguineous household contacts (68) were genotyped for the VDR TaqI polymorphism (T/t). TT and Tt genotypes were not considered to be risk factors as their odds ratios (OR) were not different from those presented by the negative Mitsuda response individuals. The combination of the tt genotype and the negative Mitsuda test provided an occurrence rate 13 times higher in leprosy patients than in controls with positive Mitsuda responses. This suggests that there is a higher risk of leprosy development when individuals carry this unfavorable combination, and demonstrates a possi...

Catalepsy is a preclinical test that predicts extrapyramidal symptoms in humans. It models sympto... more Catalepsy is a preclinical test that predicts extrapyramidal symptoms in humans. It models symptoms of acute extrapyramidal side effects induced at the beginning of antipsychotic treatment. Nitric oxide (NO) plays a role in a series of neurobiological functions underlying behavior. For example, inhibition of NO synthesis disrupts rodent exploratory behavior and induces catalepsy. Although several effects mediated by NO involve the activation of soluble guanylyl cyclase (sGC), the transduction mechanism of the catalepsy-inducing effect of NO has not yet been investigated. The study was designed to test if intracerebroventricular (i.c.v.) microinjection of NO-sensitive inhibitors of sGC (NO-sGC) induces catalepsy in mice similar to that induced by NO synthase (NOS) inhibitors. Exploratory behavior was tested in the open field. In addition, the effects of a NOS inhibitor on oxidative metabolites of NO were measured in the striatum. Drug effects were examined in the hanging-bar test after the following i.c.v. treatments: oxadiazolo-quinoxalin (ODQ, 30-300 nmol) or methylene blue (MB, 3-100 nmol), selective and nonselective sGC inhibitors, respectively, or 7-nitroindazole (7-NI, 3-90 nmol) and G-nitro-L: -arginine methyl ester (L: -NAME, 3-90 nmol), selective and nonselective neuronal NOS inhibitors. To test if the effects were related to interference with the NO system, additional groups received 7-NI (30 nmol), ODQ (100 nmol), or L-NAME (90 nmol) preceded by L: -arginine (L: -arg, 30-100 nmol, i.c.v. 30 min before). A possible interference of ODQ and 7-NI on exploratory behavior was tested in an open field. The concentration of nitrites and nitrates (NO( x )) in striatum homogenates was measured by the Griess reaction. Both NO-sGC and NOS inhibitors induced catalepsy in mice that lasted for at least 2 h. The range of effective doses of these drugs, however, was limited, and the dose-effect curves had an inverted U shape. The cataleptic effect induced by L: -NAME was inversely correlated with NO( x ) products in the striatum. The cataleptic effect of 7-NI and ODQ was prevented by pretreatment with L: -arginine. No drug changed exploratory behavior in the open field. This study showed that pharmacological disruption of the endogenous NO-sGC signaling in the central nervous system induces long-lasting catalepsy in mice. Moreover, the cataleptic effect of NOS inhibition correlates with the decrease in NO( x ) products formation in the striatum. The results give further support to the hypothesis that NO plays a role in motor behavior control mediated, at least in part, by cyclic guanosine monophosphate production in the striatum.

The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), Jan 31, 2014

Preclinical and clinical data suggest that cannabidiol (CBD), a major non-psychotomimetic compoun... more Preclinical and clinical data suggest that cannabidiol (CBD), a major non-psychotomimetic compound from Cannabis sativa, induces antipsychotic-like effects. However, the antipsychotic properties of repeated CBD treatment have been poorly investigated. Behavioral changes induced by repeated treatment with glutamate N-methyl-D-aspartate receptor (NMDAR) antagonists have been proposed as an animal model of schizophrenia-like signs. In the present study, we evaluated if repeated treatment with CBD would attenuate the behavioral and molecular modifications induced by chronic administration of one of these antagonists, MK-801. Male C57BL/6J mice received daily i.p. injections of MK-801 (0.1, 0.5, or 1mg/kg) for 14, 21, or 28 days. Twenty-four hours after the last injection, animals were submitted to the prepulse inhibition (PPI) test. After that, we investigated if repeated treatment with CBD (15, 30, and 60mg/kg) would attenuate the PPI impairment induced by chronic treatment with MK-801...

Toxicology Letters, 2012

We investigated whether high-fat diet promotes colonic dysplasia. High-fat diet increased viscera... more We investigated whether high-fat diet promotes colonic dysplasia. High-fat diet increased visceral adipose tissue. High-fat diet deregulated serotonin activity in colon tissue. High-fat diet increased dysplastic lesions and microvessels in colon tissue. High-fat diet increased proliferation and COX-2 expression in stromal colonic areas. a b s t r a c t A high-fat (HF) diet, the serotonergic system and stromal elements have all been implicated in colon carcinogenesis. We investigated whether the colonic serotonergic system could play a main role in the development of colonic dysplasia and stromal reactivity in carcinogen-treated rats under HF diet. For this, dimethylhydrazine-treated rats were fed with standard diet and a HF diet. Fat distribution was quantified by computerized tomography exam, serotonergic activity was analyzed by high-performance liquid chromatography, gene expression, and immunohistochemistry, which along with histopathological technique enabled us to enumerate dysplasia, microvessels density, cell proliferation and COX-2 expression. We found that the HF diet induced an increase in the amount of visceral adipose tissue, even without expressive changes in the average body weight. This was correlated with a loss of serotonergic balance in colon tissue. Moreover, the HF diet promoted dysplasia and microvessel density in association with increased proliferation and COX-2 expression within pericryptal colonic stroma. Our current findings suggest that a HF diet promotes the enlargement of adipose tissue via loss of control in colon serotonergic activity, which enhances colonic dysplasia by supporting microvessel development.

Toxicology Letters, 2011

Fluoxetine (FLX) is a drug commonly used as antidepressant. However, its effects on tumorigenesis... more Fluoxetine (FLX) is a drug commonly used as antidepressant. However, its effects on tumorigenesis remain controversial. Aiming to evaluate the effects of FLX treatment on early malignant changes, we analyzed serotonin (5-HT) metabolism and recognition, aberrant crypt foci (ACF), proliferative process, microvessels, vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) expression in colon tissue. Male Wistar rats received a daily FLX-gavage (30 mg kg −1 ) and, a single dose of 1,2 dimethylhydrazine (DMH; i.p., 125 mg kg −1 ). After 6 weeks of FLX-treatment, our results revealed that FLX and nor-fluoxetine (N-FLX) are present in colon tissue, which was related to significant increase in serotonin (5-HT) levels (P < 0.05) possibly through a blockade in SERT mRNA (serotonin reuptake transporter; P < 0.05) resulting in lower 5-hydroxyindoleacetic acid (5-HIAA) levels (P < 0.01) and, 5-HT2C receptor mRNA expressions. FLX-treatment decreased dysplastic ACF development (P < 0.01) and proliferative process (P < 0.001) in epithelia. We observed a significant decrease in the development of malignant microvessels (P < 0.05), VEGF (P < 0.001), and COX-2 expression (P < 0.01). These findings suggest that FLX may have oncostatic effects on carcinogenic colon tissue, probably due to its modulatory activity on 5-HT metabolism and/or its ability to reduce colonic malignant events.

Toxicology, 2013

Calorie restriction regimens usually promote health and extend life-span in mammals. This is part... more Calorie restriction regimens usually promote health and extend life-span in mammals. This is partially related to their preventive effects against malignancies. However, certain types of nutritional restriction failed to induce beneficial effects. The American Institute of Nutrition defines calorie restriction as diets which have only 40% fewer calories, but provide normal amounts of necessary food components such as protein, vitamins and minerals; whereas, food restriction means 40% less of all dietary ingredients plus 40% less calories. Our study aimed to test the hypothesis that the latter type of food deprivation (40% less food than consumed by standard fed rats) might increase cancer risk instead of reducing it, as is generally assumed for all dietary restrictive regimens. Since the endogenous modulation of the colon serotonergic system has been observed to play a role during the early steps of carcinogenesis we also investigated whether the serotoninergic system could be involved in the food intake modulation of cancer risk. For this, rats were exposed to a carcinogen and subjected to food deprivation for 56 days. Triglyceride levels and visceral adipose tissue were reduced while hepatic and colonic lipid peroxidation was increased. This dietary restriction also decreased serotonin levels in colon, and gene expression of its intestinal transporter and receptors. Finally, the numbers of preneoplastic lesions in the colon tissue of carcinogen-exposed rats were increased. Our data suggest that food deprivation enhances formation of early tumorigenic lesions by suppressing serotonergic activity in colon tissue.