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Introduction: Obesity has emerged as one of the main public health problems. This condition triggers a series of hormonal and metabolic changes related to a low-grade chronic inflammatory condition. The trypsin inhibitor purified from tamarind (TTIp) seeds is a promising anti-inflammatory molecule, but its safety needs to be evaluated. This study aimed to evaluate TTIp bioactive dose effects on organs involved in its metabolism (liver and pancreas) and affected tissues (small intestine and perirenal adipose tissue) in an obesity model. Methods: Three groups of adult male Wistar rats were used (n = 5). Two of these groups had diet-induced obesity, and a third group was eutrophic. TTIp was administered by gavage in one of the obese groups for 10 days, while the remaining groups received a vehicle. The chromatographic profile and the inhibition assay corroded the purification of the inhibitor. Physical and behavioral changes, liver enzymes, and stereological and histopathological analyses of tissues were evaluated. Results: TTIp did not cause visible signs of toxicity, nor caused changes in liver enzymes, the liver, and pancreatic tissues. TTIp did not cause changes in the intestinal mucosa, showing improvement in the villi’s histopathological characteristics compared to the group of animals with obesity without treatment with TTIp (p = 0.004). The analysis of perirenal adipose tissue showed that the average sectional area of animals with obesity that received TTIp did not differ from the control. There was a difference between the high glycemic load diet group and the group treated with the inhibitor (351.8 ± 55.5) (p = 0.016). In addition, the group that received TTIp had no inflammatory infiltrates. Conclusion: Based on histological and stereological analysis, the use of TTIp is potentially safe and anti-inflammatory in the evaluated obesity model and can be investigated as a possible adjuvant in obesity therapy.

Alcoholic neuropathy (AN), a debilitating condition that mainly affects chronic alcohol drinkers, is thought to cause lesions in the peripheral nervous system leading to sensory, autonomic, and motor dysfunctions. Despite many studies, the pathogenesis of these lesions is still not completely understood. We investigated few aspects on the development of alcohol-induced peripheral neuropathy, by assessing sensory, motor and autonomic functions, as well as stereological analysis of axonal fibers and myelin sheath of the sciatic nerve. Twelve male Wistar rats were divided into Control group and Alcohol group that was submitted to Two Bottle-Choice Paradigm of intermittent and voluntary alcohol solution intake (20%; v/v) during eight weeks. At the end of treatment, three different sensorium-motor tests were applied - Tactile Sensitivity, Thermal Sensitivity, and Functional Observational Battery (FOB). Quantitative morphometric analysis of sciatic nerve structures was performed by stereological method. Alcohol concentration in the blood was measured to analyze possible correlation between availability of alcohol in the blood and the magnitude of the peripheral nerve lesion. Our data showed a peripheral effect of chronic alcohol intake associated with hyperalgesia and a process of demyelination with a strong correlation with alcohol consumption. This process was associated with increased tactile sensitivity, with behavioral reflexes such as locomotor hyperactivity, changes in gait and balance, and autonomic reflexes such as piloerection.

Made available in DSpace on 2019-10-04T19:54:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-07-27 Fundacao de apoio a pesquisa do Estado do Rio Grande do Sul (FAPERGS) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Parkinson's disease (PD) is an age-related neurodegenerative disorder that severely affects quality of life of patients and their families. The flavonoid chrysin (5,7-dihydroxylflavone) is a naturally occurring flavone with several pharmacological activities, including anti-inflammatory and anti-oxidative. We investigated the effects of a 28-day chrysin treatment (10 mg/kg/day, i.g.) on a model of PD induced by 6-OHDA in aged (20-month old) mice. We found a protective effect of chrysin on behavioral and cognitive alterations (rotational behavior, passive avoidance and Barnes maze tests), nitric oxide synthesis (NOx), lipid peroxidation (HNE), glutathione levels (GSH), reactive species levels (RS), neuroinflammation (interleukin-1 beta - IL-1 beta and tumor necrosis factor alpha- TNF-alpha), Na+, K+-ATPase and nicotinamide adenine dinucleotide phosphate oxidase activity (NADPH oxidase) activities. In addition, chrysin protected against changes in striatal dopamine (DA), 3,4-di-hydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels. In conclusion, chrysin improved several behavioral, cognitive and neurochemical parameters in a relevant preclinical model of PD in aged mice. Fed Univ Pampa, Lab Pharmacol & Toxicol Evaluat Appl Bioact Mol L, Campus Itaqui, BR-97650000 Itaqui, RS, Brazil Fed Univ Pampa Campus, Postgrad Program Pharmaceut Sci, Uruguaiana, RS, Brazil Univ Fed Rio Grande do Norte, Biosci Ctr, Lab Neuroanat, Dept Morphol, Natal, RN, Brazil Univ Sao Paulo, Coll Vet Med & Anim Sci, Dept Surg, Lab Stochast Stereol & Chem Anat, Sao Paulo, SP, Brazil Univ Sao Paulo, Bauru Dent Sch, Dept Biol Sci, Lab Histol, Sao Paulo, SP, Brazil Sao Paulo State Univ, Lab Optimizat Sports Performance Human LaBOEH, Sao Paulo, SP, Brazil Univ Fed Santa Maria, Lab Neurotox & Psychopharmacol LABNEURO, Santa Maria, RS, Brazil Univ Fed Santa Maria, Lab Pharmacol Mycotoxins & Toxicol LAFARMT, Santa Maria, RS, Brazil Sao Paulo State Univ, Lab Optimizat Sports Performance Human LaBOEH, Sao Paulo, SP, Brazil Fundacao de apoio a pesquisa do Estado do Rio Grande do Sul (FAPERGS): 16/2551-0000526-5 Fundacao de apoio a pesquisa do Estado do Rio Grande do Sul (FAPERGS): 16/2251-0000183-9 CAPES: 001

Alcohol consumption has been identified as a causal factor promoting changes in different molecular and cellular mechanisms resulting in neurodegeneration. This process is specific to certain brain regions and its effects on different areas of the brain can result in a variety of deleterious consequences. The prefrontal cortex (PFC) appears to be particularly sensitive to alcohol-induced neurodegeneration; this region is quite complex, as it is responsible for high order mental processes such as decision making. Thus, it is important to have precise and unbiased data of neuronal morphology parameters to understand the real effects of alcohol on the PFC. This study aimed to investigate alcohol-induced neurodegeneration in the PFC by utilizing behavioral and stereological methods. In the first phase of the study, we utilized eighteen animals, six controls and twelve alcohol-treated, that were submitted to voluntary chronic alcohol ingestion for four or eight weeks. Their brains were analyzed by design-based stereology methods to assess number and volume parameters regarding neuronal integrity in regions of the PFC (prelimbic - PL, infralimbic - IL and anterior cingulate - ACC). In the second phase of the study, six animals were utilized as controls and eight animals were submitted to the same alcohol ingestion protocol and to a behavioral decision-making test. In conclusion, our findings indicate that chronic alcohol consumption promotes a decrease in volume in the prelimbic and in the anterior cingulate, a decrease of mean neuronal volume in the anterior cingulate cortex and a decrease of total volume of neurons in the IL area. We did not observe changes in decision-making behavior in either of the two periods of alcohol intake. This shows that morphological changes occur in specific regions of the prefrontal cortex, a noble area of cognitive functions, induced by chronic alcohol consumption.

Diabetes mellitus (DM) is a metabolic disease associated with several intestinal disorders. S-methyl cysteine sulfoxide (SMCS) ​​is an amino acid present in Allium cepa L with hypoglycemic effects. However, the effects of SMCS on diabetic intestinal changes are unknown. Thus, we aimed to investigate the effects of SMCS on duodenal morphology and immunomodulatory markers in diabetic rats. Twenty-six rats were divided into three groups: control (C), diabetic (D) and diabetic +200 mg/kg SMCS (DSM). DM was induced by intraperitoneal injection of streptozotocin (50 mg/kg). After 30 days, duodenum samples were processed to assess histopathological and stereological alterations in volume, villus length, and immunohistochemical expression of NF-kB, IL-10, BCL-2, and caspase-3. SMCS reduced hyperglycemia and mitigated the increase in total reference volume of the duodenum, the absolute volume of the mucosa, and the length of the intestinal crypts in the DMS group when compared to D. IL-10 immunostaining was reduced in D when compared to C, while NF-kB was increased in D in comparison to the other groups. SMCS ​​supplementation could decrease the NF-kB immunostaining observed in D. Positive staining for BCL-2 and caspase-3 were not statistically different between groups. In summary, SMCS decreased hyperglycemia and mitigated the morphological changes of the duodenum in diabetic animals, and these beneficial effects can be partially explained by NF-kB modulation.

Hesperidin is a flavonoid glycoside that is frequently found in citrus fruits. Our group have demonstrated that hesperidin has neuroprotective effect in 6-hydroxydopamine (6-OHDA) model of Parkinson’s disease (PD), mainly by antioxidant mechanisms. Although the pathophysiology of PD remains uncertain, a large body of evidence has demonstrated that mitochondrial dysfunction and apoptosis play a critical role in dopaminergic nigrostriatal degeneration. However, the ability of hesperidin in modulating these mechanisms has not yet been investigated. In the present study, we examined the potential of a 28-day hesperidin treatment (50 mg/kg/day, p.o.) in preventing behavioral alterations induced by 6-OHDA injection via regulating mitochondrial dysfunction, apoptosis and dopaminergic neurons in the substantia nigra pars compacta (SNpc) in C57BL/6 mice. Our results demonstrated that hesperidin treatment improved motor, olfactory and spatial memory impairments elicited by 6-OHDA injection. Moreover, hesperidin treatment attenuated the loss of dopaminergic neurons (TH+ cells) in the SNpc and the depletion of dopamine (DA) and its metabolities 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum of 6-OHDA-lesioned mice. Hesperidin also protected against the inhibition of mitochondrial respiratory chain complex-I, -IV and V, the decrease of Na + -K + -ATPase activity and the increase of caspase-3 and -9 activity in the striatum. Taken together, our findings indicate that hesperidin mitigates the degeneration of dopaminergic neurons in the SNpc by preventing mitochondrial dysfunction and modulating apoptotic pathways in the striatum of 6-OHDA-treated mice, thus improving behavioral alterations. These results provide new insights on neuroprotective mechanisms of hesperidin in a relevant preclinical model of PD.

The objective of this study was to evaluate effects of eCG on vascularization and development of feline ovarian tissue xenografted to immunosuppressed mice. Feline ovarian fragments (∼1 mm3) were transplanted under the renal capsule of 20 adult, ovariectomized, C57BL/6 SCID female mice. At 45 d after transplantation, 10 mice (controls) were euthanized and the remainder given 10 IU of eCG (and sacrificed 48 h later). Transplants were recovered immediately after death, fixed, sectioned, and stained with periodic acid-Schiff (PAS). Fragment volume (Cavallieri principle) and vascularization were assessed. Mean xenotransplant volume for control and treatment groups was 0.17 ± 0.03 and 0.37 ± 0.13 mm3, respectively (P = 0.0952); vascular volume density, 30.3 ± 11.3 and 49.1 ± 8.9% (P = 0.0281); surface density, 4.1 ± 2.4 and 6.2 ± 1.7 μm−1 (P = 0.2222); and vessel total surface, 0.63 ± 0.24 μm2 and 2.28 ± 1.05 μm2 (P = 0.0079). In conclusion, eCG significantly increased vascular volume density of xenotransplanted ovarian tissue and improved its development.

Chrysin is a natural flavonoid which is found in bee propolis, honey and various plants, and neuroprotective effect of chrysin in mice was previously demonstrated by our group. Neuroinflammation, neurotrophic factors and neuronal recovery factors associated with the neuroprotective effect of this flavonoid require further investigations. Thus, now we investigated the possible involvement of inflammatory cytokines, neurotrophic factors and neuronal recovery in the effect of chrysin in 6-hydroxidopamine (6-OHDA), a well-established model of Parkinson's disease, in striatum of mice. The 6-OHDA microinjection induced behavioral alterations on the rotarod test and apomorphine-induced circling behavior in mice. 6-OHDA administration elevated levels of tumour necrosis factor-α, interferon-gamma, interleukin-1β, interleukin-2, interleukin-6 and nuclear factor-kappa B and decreased the interleukin-10 levels, total reactive antioxidant potential and total antioxidant reactivity in striatum, as well as, modified the calcium-binding protein B (S100B), brain-derived neurotrophic factor, nerve growth factor and glial cell line-derived neurotrophic factor levels. The intrastriatal injection of 6-OHDA also induced an decrease of dopamine, 3,4-dihydroxyphenylacetic acid, homovanylic acid levels and tyrosine hydroxylase content. Oral treatment with chrysin (10 mg/kg, 28 days), culminated with the prevention of these alterations occasioned by 6-OHDA. These results corroborated with the neuroprotective effect of chrysin in the treatment of Parkinson's disease and, indicated the mechanism involved throught the inflammatory cytokines, neurotrophic factors and recovery of dopaminergic neurons in striatum.

The mechanisms underlying the neuroprotective effects of hesperidin in a murine model of PD are not fully elucidated. The current study was carried out to investigate the ability of hesperidin in modulating proinflammatory cytokines, neurotrophic factors, and neuronal recovery in 6-hydroxydopamine (6-OHDA)-induced nigral dopaminergic neuronal loss. Adult male C57BL/6 mice were randomly assigned into four groups: (I) sham/vehicle, (II) sham/hesperidin, (III) 6-OHDA/vehicle, and (IV) 6-OHDA/hesperidin. Mice received a unilateral intrastriatal injection of 6-OHDA and treated with hesperidin (50 mg/kg; per oral) for 28 days. After hesperidin treatment, mice were submitted to behavioral tests and had the striatum removed for neurochemical assays. Our results demonstrated that oral treatment with hesperidin ameliorated the anxiety-related and depressive-like behaviors in 6-OHDA-lesioned mice (p

The increasing prevalence of obesity and, consequently, chronic inflammation and its complications has increased the search for new treatment methods. The effect of the purified tamarind seed trypsin inhibitor (TTIp) on metabolic alterations in Wistar rats with obesity and dyslipidemia was evaluated. Three groups of animals with obesity and dyslipidemia were formed, consuming a high glycemic index and glycemic load (HGLI) diet, for 10 days: Obese/HGLI diet, Obese/standard diet, Obese/HGLI diet + TTIp (730 &mu, g/kg), and one eutrophic group of animals was fed a standard diet. Rats were evaluated daily for food intake and weight gain. On the 11th day, animals were anesthetized and sacrificed for blood and visceral adipose tissue collection. TTIp treated animals presented significantly lower food intake than the untreated group (p = 0.0065), TG (76.20 &plusmn, 18.73 mg/dL) and VLDL-C (15.24 &plusmn, 3.75 mg/dL). Plasma concentrations and TNF-&alpha, mRNA expression in visceral adipose tissue also decreased in obese animals treated with TTIp (p &lt, 0.05 and p = 0.025, respectively) with a negative immunostaining. We conclude that TTIp presented anti-TNF-&alpha, activity and an improved lipid profile of Wistar rats with dyslipidemia and obesity induced by a high glycemic index and load diet regardless of PPAR-&gamma, induction.

We investigated the inflammatory effect of a pellet-diet with high glycemic index and load (HGLI) on the histological organization of adipocytes, intestinal epithelium, and fat in liver and pancreas in adult male Wistar rats. Two groups (n=10) received for 17 weeks: (1) HGLI diet or (2) Standard diet (Labina®). Histological analyses of adipose tissue, jejunum, liver, and pancreas were performed. Stereology analysis, visceral adiposity index, gene expression, and immunohistochemistry of tumor necrosis factor-α (TNF-α) in visceral adipose tissue and plasma TNF-α were also assessed. The HGLI diet-induced hypertrophy of adipocytes with adipocyte volume density equal to 97.0%, cross-sectional area of adipocytes equivalent to 1387 µm² and a total volume of adipocytes of 6.97 cm³ an elevation of 8%, 25%, and 58%, respectively. Furthermore, the HGLI diet increased liver and pancreatic fat deposition, altered and inflamed the intestinal epithelia, and increased TNF-α gene expression (P=0.014) with a positive immunostaining in visceral adipose tissue and high plasma TNF-α in comparison with standard diet. The results suggest that this diet was able to generate changes commonly caused to solid diets with high fat or fructose-rich beverages. To the best of our knowledge, this is the first report in the literature concerning the properties of low-cost, sucrose-rich pellet-diet presenting high glycemic index and high glycemic load efficient on the development of obesity complications in Wistar rats that were subjected to diet-induced obesity. Therefore, the HGLI pellet-diet may be considered an effective tool to be used by the scientific community in experimental research.

In mammals, the suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL) are the main components of the circadian timing system. The SCN, classically known as the master circadian clock, generates rhythms and synchronizes them to environmental cues. The IGL is a key structure that modulates SCN activity. Strategies on the use of time by animals can provide important clues about how some species are adapted to competitive process in nature. Few studies have provided information about temporal niche in bats with special attention on the neural substrate underlies circadian rhythms. The aim of this study was to investigate these circadian centers with respect to their cytoarchitecture, chemical content and retinal projections in the flat-faced fruit-eating bat (Artibeus planirostris), a chiropteran endemic to South America. Unlike other species of phyllostomid bats, the flat-faced fruit-eating bat's peak of activity occurs 5 h after sunset. This raises several questions about the structure and function of the SCN and IGL in this species. We carried out a mapping of the retinal projections and cytoarchitectural study of the nuclei using qualitative and quantitative approaches. Based on relative optical density findings, the SCN and IGL of the flat-faced fruit-eating bat receive bilaterally symmetric retinal innervation. The SCN contains vasopressin (VP) and vasoactive intestinal polypeptide (VIP) neurons with neuropeptide Y (NPY), serotonin (5-HT) and glutamic acid decarboxylase (GAD) immunopositive fibers/terminals and is marked by intense glial fibrillary acidic protein (GFAP) immunoreactivity. The IGL contains NPY perikarya as well as GAD and 5-HT immunopositive terminals and is characterized by dense GFAP immunostaining. In addition, stereological tools were combined with Nissl stained sections to estimate the volumes of the circadian centers. Taken together, the present results in the flat-faced fruit-eating bat reveal some differences compared to other bat species which might explain the divergence in the hourly activity among bats in order to reduce the competitive potential and resource partitioning in nature.

The dopamine (DA) neurons of the retrorubral field (RRF - A8), the substantia nigra (SN - A9), and the ventral tegmental area (VTA - A10) have been implicated in motor regulation, reward, aversion, cognition, and several neuropsychiatric disorders. A series of studies have identified subdivisions of these cell groups in rodents, but these cell groups have not been well described in bats. An understanding of the motor system organization in bats would provide a context for comparing motor systems across rodent, primate, and bat phylogenies. The aim of this work was to determine whether typical subdivisions of RRF, SN, and VTA are present in Artibeus planirostris, a common frugivorous bat species found throughout South America. Coronal and sagittal sections of bat brain were subjected to Nissl staining and TH immunohistochemistry. The organizational pattern of the nuclei in A. planirostris showed a conspicuous tail in the SN, which has been not described in bats to date, and also contained a well-defined substantia nigra reticulata (SNR) not previously reported in microbats. This work provides for the first time a morphometric analysis of DA neurons in a microchiropteran species, enabling a comparative investigation of vertebrates. Our analysis revealed an apparent phylogenetic stability in these structures, although the SN tail might represent a functional specialization in this species.

O presente estudo analizou nove gânglios cervicais craniais esquerdos (GCC) de Cutias (Dasyprocta aguti) machos oriundos do criatório da Universidade Federal Rural do Semi Árido Nordestino de Mossoró- RN. Nestes animais foi estimado o número total dos neurônios (mono e binucleados), bem como seus volumes, volume do gânglio, a densidade neuronal e densidade de volume neuronal durante o desenvolvimento pós-natal (maturação): animais neonatos, jovens e adultos. Os GCCs foram fixados com solução de formoldeído (4%) em PBS, embebidos em solução de ágar e seccionados sistemática, uniforme e aleatoriamente para a aplicação dos métodos estereológicos entre os quais disector e rotator ópticos. para a estimativa da densidade e do volume neuronal, respectivamente. Houve diferença significativa entre os grupos etários para os parâmetros: volume ganglionar, número total de neurônios binucleados, volume neuronal médio de neuronios mono e binucleados e densidade de volume neuronal. A conclusão é de que a idade influencia quantitativamente a dinamica neuronal do GCC de cutias e futuramente estes dados servirão como base para a investigação da ocorrência de divisão celular durante o período pós-natal em roedores. The present study was pursued in nine left cranial cervical ganglia (CCG) of male cutias (Dasyprocta aguti) obtained from the animal house of the Universidade Federal Rural do Semi-Árido Nordestina em Mossoró- RN. The number of CCG neurons as well as their volume, ganglion volume, numerical density and neuronal volume density were estimated during the post-natal development (maturation), in neonates, young and adult animals, by using 3-D design-based stereological methods, e.g., optical disector and optical rotator. Briefly, CCGs were fixed with a 4% formaldehyde solution in PBS, embedded in a 10% agar solution and exhaustively vibrosectioned (SURS) in order to accordingly perform the relevant stereological estimations. There were significant difference between age groups for the follow parameters: ganglion volume, total number of binucleated neurons, mean neuronal volume of mono and binucleated neurons and volume density of neurons. The conclusion is of that the age quantitative influences the dinamic of neuronal cells of the GCC of agoutis. In the future these data will serve as basis for the inquiry of the occurrence of cellular division during the post-natal period in rodents.