Fumonisin-containing diets decrease the metabolic activity of myenteric neurons in rats.

Fumonisins are naturally occurring mycotoxins that contaminate food for human and animal consumption. They have neurotoxic effects, but the mechanisms by which these toxins affect the nervous system are not fully known. In the present study, male Wistar rats were fed between 21 and 63 days of age with diets that contained fumonisins B1+B2 at 0, 1, and 4 mg/kg. The following variables were assessed: food consumption, growth, body weight gain, and blood parameters. Morphoquantitave analyses of the most metabolically active myenteric neurons were performed, detected by NADH-diaphorase activity. Nitrergic neurons were detected by NADPH-diaphorase activity. The fumonisin-containing diets did not significantly alter food consumption or the body or plasma parameters. These diets decreased the metabolic activity of jejunal myenteric neurons, reducing neuronal density of the most metabolic active neurons by 30.8% and the cell body area by 4.3%. The diets also decreased the cell body area of nitrergic neurons by 22.1%. The effects of fumonisin B1 on the respiratory metabolism of isolated mitochondria in the brain and liver were also assessed. A decrease in oxygen consumption up to a 29% in the brain and 38% in the liver was observed in mitochondrial isolates to which 50 µM fumonisin B1 was added. The decrease in respiratory activity that was triggered by exposure to fumonisins was related to the lower metabolic activity of myenteric neurons, which had a negative impact on neuroplasticity of the enteric nervous system.

Insulin degludec and glutamine dipeptide modify glucose homeostasis and liver metabolism in diabetic mice undergoing insulin-induced hypoglycemia.

This study investigated whether a 30-day co-treatment with 1 g/kg glutamine dipeptide (GdiP) and 1 U/kg regular (rapid acting) or 5 U/kg degludec (long acting) insulins modifies glucose homeostasis and liver metabolism of alloxan-induced type 1 diabetic (T1D) male Swiss mice undergoing insulin-induced hypoglycemia (IIH). Glycemic curves were measured in fasted mice after IIH with 1 U/kg regular insulin. One hour after IIH, the lipid profile and AST and ALT activities were assayed in the serum. Morphometric analysis was assessed in the liver sections stained with hematoxylin-eosin and glycolysis, glycogenolysis, gluconeogenesis and ureagenesis were evaluated in perfused livers. T1D mice receiving GdiP or the insulins had a smaller blood glucose drop at 60 minutes after IIH, which was not sustained during the subsequent period up to 300 minutes. The 30-day treatment of T1D mice with insulin degludec, but not with regular insulin, improved fasting glycemia, body weight gain and serum activity of AST and ALT. Treatments with insulin degludec, GdiP and insulin degludec + GdiP decreased the liver capacity in synthesizing glucose from alanine. GdiP, in combination with both insulins, was associated with increases in the serum triglycerides and, in addition, regular insulin and GdiP increased AST and ALT activities, which could be the consequence of hepatic glycogen overload. GdiP and the insulins improved the IIH, although to a small extent. Caution is recommended, however, with respect to the use of GdiP because of its increasing effects on serum triglycerides and AST plus ALT activities.

Whey protein enriched with Stevia rebaudiana fraction restores the pancreatic function of streptozotocin induced diabetic rats.

The study aims to analyse the treatment of whey protein enriched with Stevia rebaudiana fraction in insulin secretion and its role mitigating streptozotocin-induced hyperglycemia in rats. Thus, diabetic animals were treated with whey protein enriched with S. rebaudiana fraction or with only the protein isolate or only the Stevia fraction. Insulin level in plasma was measured by radioimmunoassay and the viability of ß cells was detected by immunohistochemistry. The results showed that diabetic animals treated with whey protein enriched with S. rebaudiana fraction had a greater recovery from insulinemia, with plasma levels similar to non-diabetic animals (~ 0.13 ng/mL). In addition, the same group showed a higher number of insulin-positive pancreatic B cells (~ 66%) in immunohistochemistry analysis, while the diabetic groups treated with only the fraction of stevia or whey protein showed 38 and 59% of positive cells, respectively. These results show that the treatment may have restored the viability of streptozotocin-injured pancreatic B cells, and consequently increased insulin secretion, suggesting whey protein enriched with S. rebaudiana fraction can be used an adjunct/supplement in diabetic treatment.

Particulate Matter Exposure During Perinatal Life Results in Impaired Glucose Metabolism in Adult Male Rat Offspring.

BACKGROUND/AIMS: Particulate matter (PM) is an important risk factor for immunological system imbalance due to its small size, which can reach more distal regions of the respiratory tract, independently of its chemical composition. Some studies have suggested that PM exposure is associated with an increased incidence of diabetes, especially in industrialized urban regions. However, studies regarding the effects of PM exposure during perinatal life on glucose metabolism are limited. We tested whether exposure to PM from an urban area with poor air quality during pregnancy and lactation could cause short- and long-term dysfunction in rat offspring. METHODS: Samples of < 10 µm PM were collected in an urban area of Cotonou, Benin (West Africa), and reconstituted in corn oil. Pregnant Wistar rats received 50 µg PM/day by gavage until the end of lactation. After birth, we analyzed the dams' biochemical parameters as well as those of their male offspring at 21 and 90 days of age. RESULTS: The results showed that PM exposure did not lead to several consequences in dams; however, the male offspring of both ages presented an increase of approximately 15% in body weight. Although the blood glucose levels remained unchanged, the insulin levels were increased 2.5- and 2-fold in PM exposure groups of both ages, respectively. HOMA-IR and HOMA-ß were also increased at both ages. We also demonstrated that the number, islet area and insulin immunodensity of pancreatic islets were significantly increased at both ages from PM exposure. CONCLUSION: Our data show that chronic PM exposure by the oral route during perinatal life in rats leads to glucose dyshomeostasis in male offspring both in early and later life. Thus, we suggest that an ambience with poor air quality, mainly where traffic is dense, can contribute to an increase in metabolic disease incidence.

Sex differences in the development of hepatic steatosis in cafeteria diet-induced obesity in young mice.

The present study was planned to improve our understanding about sex differences in the development of hepatic steatosis in cafeteria diet-induced obesity in young mice. Female (FCaf) and male (MCaf) mice fed a cafeteria diet had similar body weight gain and adiposity index, but FCaf had a more extensive steatosis than MCaf. FCaf livers exhibited a higher non-alcoholic fatty liver disease activity score, elevated lipid percentage area (+34%) in Sudan III staining and increased TG content (+25%) compared to MCaf. Steatosis in FCaf was not correlated with changes in the transcript levels of lipid metabolism-related genes, but a reduced VLDL release rate was observed. Signs of oxidative stress were found in FCaf livers, as elevated malondialdehyde content (+110%), reduced catalase activity (-36%) and increased Nrf2 and Hif1a mRNA expression compared to MCaf. Interestingly, fibroblast growth factor 21 (Fgf21) mRNA expression was found to be exclusively induced in MCaf, which also exhibited higher FGF21 serum levels (+416%) and hepatic protein abundance (+163%) than FCaf. Moreover, cafeteria diet increased Fgfr1, Fsp27 and Ucp1 mRNA expression in brown adipose tissue of males (MCaf), but not females (FCaf). FGF21 hepatic production by male mice seems to be part of a complex network of responses to the nutritional stress of the cafeteria diet, probably related to the unfolded protein response activation. Although aimed at the restoration of hepatic metabolic homeostasis, the branch involving Fgf21 upregulation seems to be impaired in females, rendering them incapable of reducing the hepatic lipid content and cellular oxidative stress.

Development and characterization of multiple emulsions for controlled release of Trichilia catigua (Catuaba) extract.

Considering the antioxidant activity of the Trichilia catigua extract (TCE), the aim of the current study was to develop and characterize W/O/W multiple emulsions containing different vegetable oils as a platform to deliver a TCE. The extract displayed antioxidant activity (IC50) of 4.59 µg/mL and total phenol content (TPC) of 50.84%. Formulations were prepared by the phase-inversion emulsification method and analyzed for morphological appearance, pH, conductivity, droplet size and distribution, content of active, rheological properties, in vitro release, skin permeation, and stability. Formulations prepared with canola oil were selected and displayed regular morphology, mean diameter 2.77 µm (without TCE), 3.07 µm with 0.5% and 3.23 µm with 1.0% TCE. Rheometry (flow) showed pseudoplastic behavior with minimal thixotropy for both systems. TCE could be released from emulsions containing 1.0% and 0.5% TCE in a controlled manner for 16 and 23 h, respectively. The emulsions allowed good retention of TCE in the skin (stratum corneum, epidermis, and dermis). In a 180-d assessment of accelerated chemical stability, TPC was more reduced for the emulsions at 40 °C; other parameters remained stable. Multiple emulsions containing TCE were developed, exhibited good characteristics, and may be considered for future investigations as anti-aging formulations for the skin.

High-fat diet promotes neuronal loss in the myenteric plexus of the large intestine in mice.

BACKGROUND: Obesity is considered a risk factor for other chronic diseases, and diets rich in lipids can cause alterations in the intestinal functions. AIM: The aim of this study was to investigate the effects of a high-fat diet (HFD) on the myenteric plexus of the large intestine in mice. METHODS: Swiss mice were distributed into four groups: Control animals fed standard chow for 8 and 17 weeks (C8 and C17 groups) and hyperlipidic animals fed HFD for 8 and 17 weeks (Ob8 and Ob17 groups). Immunofluorescence was performed in the large intestine for the morphologic and quantitative analysis of neuronal populations. RESULTS: Animals in the Ob17 group exhibited increased body weight and visceral fat gain compared with the C17 group. The intestinal area was also reduced in the two Ob groups. In the proximal colon, the Ob17 group exhibited 16.1 % reduction of the general neuronal density and 33 % reduction of the VIP-immunoreactive (IR) subpopulation. The general neuronal density in the distal colon was reduced by 45 % in the Ob17 group, and the nNOS-IR density was reduced by 35 %. The morphometry of neuronal cell bodies in the Ob17 group exhibited a reduction of the neuronal area of all of the neuronal populations studied in the proximal colon, with a reduction of the subpopulations of nNOS-IR and VIP-IR neurons in the distal colon. CONCLUSIONS: The HFD caused neuronal loss in the myenteric plexus, and nitrergic neurons were more resilient. The changes were more pronounced in the distal colon after 17 weeks.

Resveratrol Reduces Morphologic Changes in the Myenteric Plexus and Oxidative Stress in the Ileum in Rats with Ischemia/Reperfusion Injury.

BACKGROUND: Intestinal ischemia/reperfusion injury can be caused by surgical procedures and inflammatory bowel disease. It is normally associated with the increased production of free radicals and changes in the enteric nervous system. AIMS: Given the antioxidant and neuroprotective properties of resveratrol, the present study assessed its influence on oxidative stress in the intestinal wall and the morphology of myenteric neurons in the ileum of rats subjected to ischemia/reperfusion. METHODS: Resveratrol was orally administered daily at a dose of 10 mg/kg for 5 days. Changes in the ileum response to ischemia after 45 min were investigated followed by 3 h reperfusion. Lipoperoxide and carbonylated protein levels, and the activity of the antioxidant enzymes glutathione reductase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase were measured following ischemia/reperfusion injury. RESULTS: The density and morphometry of the general neuronal population, nitrergic neurons and glial cells, and morphometry of VIP varicosities in the ileum were also studied. Lipoperoxide and carbonylated protein levels were 171 and 40% higher during the ischemia/reperfusion, respectively, compared to control cohorts, and resveratrol attenuated these values. The glutathione ratio was 64% lower during ischemia/reperfusion, compared to control cohorts. Resveratrol increased the reduced/oxidized glutathione ratio, attenuated the changes in the activity of the antioxidant enzymes and the detrimental morphologic changes caused by ischemia/reperfusion in the general neuronal population and nitrergic neurons. CONCLUSIONS: Oral treatment with resveratrol reduced the oxidative stress in the ileum and attenuated the morphologic changes that occurred in the myenteric plexus of the ileum in rats subjected to ischemia/reperfusion.

Morpho-functional response of Nile tilapia (Oreochromis niloticus) to a homeopathic complex.

BACKGROUND: This study evaluated the performance, prevalence of ectoparasites and morpho-functional response of the liver and the branchiae of Nile tilapia (Oreochromis niloticus) raised on fish meal with added of the homeopathic complex Homeopatila 100(®) at different concentrations. METHODS: Post-reversed juvenile Nile tilapia (O. niloticus) of the GIFT (Genetic Improvement of Farmed Tilapia) strain were used in this study. The performance, ectoparasite prevalence and parasite load in the branchiae and skin as well as the liver and branchial histology. Fish were randomly assigned to receive one of four treatments: control, 20 mL hydroalcoholic solution (alcohol 30° GL); 20 mL Homeopatila 100(®) per kg of meal; 40 mL Homeopatila 100(®) per kg of meal; or 60 mL of Homeopatila 100(®) per kg of meal, compared to control with out the addition of the complex. There were four replications per treatment type (16 experimental units total) at a density of 40 fish per m(3) over a period of 57 days. The Kruskal-Wallis H test (p < 0.05) was employed to analyse the physical and chemical parameters of water as well as for parasite prevalence; whereas analysis of variance was used for liver performance. If the values were significant (p < 0.05), they were compared by Tukey's test. Multiple comparisons of averages were performed using Student's t test (p < 0.05). RESULTS: There were no significant between the physical and chemical parameters of the water between the different groups at the end of the experiment. Significant differences (p < 0.05) in the mixed parasite conditions were found within the different Homeopatila 100(®) treatments. The hepatosomatic ratio of fish treated with Homeopatila 100(®) was significantly lower than that of fish from the control group. The best results in the liver and branchiae occurred in fish receiving Homeopatila 100(®) at 40 mL/kg in terms of the number of hepatocytes/mm(2), the intercellular glycogenic behaviour, the rates of histological changes (hyperplasia, lamella fusion and telangiectasia) and the percentage of neutral and acidic mucin-producing cells. CONCLUSION: The addition of Homeopatila 100(®) at a concentration 40 mL per kg/meal to the diet of juvenile Nile tilapias resulted in improved hepatocytes and intracellular glycogen levels as well as the lowest mean rate of branchial histological changes with an increase in acidic mucin-producing cells compared to neutral mucin-producing cells, compared to control.

Chronic ingestion of deoxynivalenol-contaminated diet dose-dependently decreases the area of myenteric neurons and gliocytes of rats.

BACKGROUND: Deoxynivalenol (DON), a mycotoxin produced by Fusarium spp., is commonly found in cereals ingested by humans and animals. Its ingestion is correlated with hepatic, hematologic, renal, splenic, cardiac, gastrointestinal, and neural damages, according to dose, duration of exposure and species. In this work, the effects of the ingestion of DON-contaminated diet at concentrations considered tolerable for human and animal intake were assessed. METHODS: Male Wistar rats aging 21 days were allotted to five groups that were given, for 42 days, diets contaminated with different concentrations of DON (0, 0.2, 0.75, 1.75, and 2 mg kg-1 of chow). Food ingestion, bodyweight, oxidative status and morphometric analyses of gliocytes, and neurons of jejunal myenteric ganglia were recorded. KEY RESULTS: At these concentrations, there was no food rejection, decrease in bodyweight gain, changes in oxidative status, or loss of either neurons or gliocytes. However, DON decreased gliocyte area, general neuronal population, nitrergic, cholinergic and NADH-diaphorase positive subpopulations and, as a result, ganglion area. CONCLUSIONS & INFERENCES: It was concluded that, even in the absence of visible effect, DON exposure reduces cell body area of gliocytes and neurons of the myenteric plexus of the rat jejunum.

Sericin as treatment of obesity: morphophysiological effects in obese mice fed with high-fat diet.

OBJECTIVE: To investigate the effects of sericin extracted from silkworm Bombyx mori cocoon on morphophysiological parameters in mice with obesity induced by high-fat diet. METHODS: Male C57Bl6 mice aged 9 weeks were allocated to one of two groups - Control and Obese, and fed a standard or high-fat diet for 10 weeks, respectively. Mice were then further subdivided into four groups with seven mice each, as follows: Control, Control-Sericin, Obese, and Obese-Sericin. The standard or high fat diet was given for 4 more weeks; sericin (1,000mg/kg body weight) was given orally to mice in the Control-Sericin and Obese-Sericin Groups during this period. Weight gain, food intake, fecal weight, fecal lipid content, gut motility and glucose tolerance were monitored. At the end of experimental period, plasma was collected for biochemical analysis. Samples of white adipose tissue, liver and jejunum were collected and processed for light microscopy analysis; liver fragments were used for lipid content determination. RESULTS: Obese mice experienced significantly greater weight gain and fat accumulation and had higher total cholesterol and glucose levels compared to controls. Retroperitoneal and periepididymal adipocyte hypertrophy, development of hepatic steatosis, increased cholesterol and triglyceride levels and morphometric changes in the jejunal wall were observed. CONCLUSION: Physiological changes induced by obesity were not fully reverted by sericin; however, sericin treatment restored jejunal morphometry and increased lipid excretion in feces in obese mice, suggesting potential anti-obesity effects.

Evaluation of anti-HSV-1 activity and toxicity of hydroethanolic extract of Tanacetum parthenium (L.) Sch.Bip. (Asteraceae).

BACKGROUND: Herpes simplex type 1 (HSV-1) is widely distributed throughout the world's population. The virus spreads through direct contact with an infected individual. After primary infection, the virus remains in a latent state, and the recurrence of herpetic lesions is common. Standard treatment is performed with nucleoside analogues, but the selection of resistant strains have occurred, thus requiring the continual search for new antiviral agents. Plant extracts, fractions, and isolated compounds are a good source for studying possible antiviral compounds. HYPOTHESIS: Among plants with antiviral activity, the crude extract of aerial parts of Tanacetum parthenium (L.) Sch.Bip. (Asteraceae) have previously shown to inhibit HSV-1 infection in vitro. METHODS: The present study investigated the chemical composition of a crude hydroethanolic extract (CHE) of T. parthenium, and in vivo safety and therapeutic efficacy against HSV-1 infection. RESULTS: Liquid chromatography-mass spectrometry showed that the CHE was composed of phenolic acids (chlorogenic acids) and sesquiterpene lactones (parthenolide). Acute and subchronic toxicity and genotoxicity tests in vivo showed that oral CHE administration did not result in signs of toxicity, with no genotoxic potential. The CHE was also safe for topical administration, in which no irritation of the epidermis was observed in treated animals. Tests of topical and oral therapeutic efficacy showed that the CHE was effective against HSV-1 infection. Topical administration was the most effective, the results for which were comparable to acyclovir. CONCLUSION: These findings indicate that the CHE from aerial parts of Tanacetum parthenium has in vivo anti-HSV-1 activity and is safe for oral and topical application.

Myenteric neurons and intestinal mucosa of diabetic rats after ascorbic acid supplementation.

AIM: To investigate the effect of ascorbic acid (AA) dietary supplementation on myenteric neurons and epithelial cell proliferation of the jejunum of adult rats with chronic diabetes mellitus. METHODS: Thirty rats at 90 d of age were divided into three groups: Non-diabetic, diabetic and diabetic treated with AA (DA) (1 g/L). After 120 d of treatment with AA the animals were killed. The myenteric neurons were stained for myosin-V and analyzed quantitatively in an area of 11.2 mm(2)/animal. We further measured the cellular area of 500 neurons per group. We also determined the metaphasic index (MI) of the jejunum mucosa layer of about 2500 cells in the intestinal crypts, as well as the dimensions of 30 villi and 30 crypts/animal. The data area was analyzed using the Olympus BX40 microscope. RESULTS: There was an increase of 14% in the neuronal density (792.6 +/- 46.52 vs 680.6 +/- 30.27) and 4.4% in the cellular area (303.4 +/- 5.19 vs 291.1 +/- 6.0) respectively of the diabetic group treated with AA when compared to control diabetic animals. There were no significant differences in MI parameters, villi height or crypt depths among the groups. CONCLUSION: Supplementation with AA in the diabetic animal promoted moderate neuroprotection. There was no observation of alteration of the cellular proliferation of the jejunum mucosa layer of rats with chronic diabetes mellitus with or without supplementation with AA.

Resveratrol promotes neuroprotection and attenuates oxidative and nitrosative stress in the small intestine in diabetic rats.

Damages to the enteric nervous system caused by diabetes mellitus (DM) are frequently attributed to oxidative and nitrosative stress. We aimed to investigate the effect of Resveratrol (RSV) (10 mg/kg) on oxidative and nitrosative stress in the intestinal wall and morphoquantitative aspects of the myenteric plexus of the duodenum, jejunum and ileum in diabetic rats. Twenty-four rats were distributed into four groups (n = 6/group): control (C group), control treated with RSV (CR group), diabetic (D group), and diabetic treated with RSV (DR group) for 120 days. Immunohistochemical staining techniques for the general neuronal population, nitrergic and calretinin neuronal subpopulations, enteric glial cells and glial fibrillary acid protein were performed in the myenteric plexus. Furthermore, parameters of oxidative and nitrosative stress were analyzed in the intestinal wall. RSV attenuated oxidative and nitrosative stress and prevented neuronal loss and hypertrophy of the HuC/D-IR, nNOS-IR and CALR-IR neuronal subpopulations in the DR group compared with the D group (P < 0.05). In addition, RSV prevented the increase in glial fibrillary acid protein fluorescence in the DR group compared with the D (P < 0.05). These results suggest that RSV has antioxidant and neuroprotective effects in myenteric plexus in rats with experimental DM.

Methyl jasmonate: a phytohormone with potential for the treatment of inflammatory bowel diseases.

OBJECTIVES: The phytohormone methyl jasmonate (MeJA) has been identified as a vital cell regulator in plants. This substance is analogous to eicosanoids and similar to that of anti-inflammatory prostaglandins. In animals and in animal cells, it displayed an efficient neuroprotective, anti-inflammatory and antioxidant action; while in tumoral strains, it demonstrates a potentially highly attractive mechanism of apoptosis induction through various cellular and molecular mechanisms. The aim of the present review was to explore two new hypotheses that explain the action of MeJA, a lipid phytohormone and its potentially anti-apoptotic mechanism for use as a therapeutic target for future treatment of Inflammatory bowel diseases (IBDs). KEY FINDINGS: Methyl jasmonate is a new candidate for the treatment of IBDs, modulating the expression of the major classes of caspase-type protease families that selectively act on the extrinsic and intrinsic pathways of the apoptotic process. Its action is based on the reduction of the expression in tumour necrosis factor tissue levels and the modulating action of reactive oxygen species production, acting only on the destruction of cells that express the diseased phenotype, and preserving cells that are not transformed. CONCLUSIONS: Methyl jasmonate may represent an alternative for the transduction processes of important signals in the cellular renewal of the intestinal mucosa.

Treatment with Trichilia catigua ethyl-acetate fraction improves healing and reduces oxidative stress in TNBS-induced colitis in rats.

Beverages containing Trichilia catigua are commonly employed in folk medicine. T. catigua bark extracts possess antioxidant, anti-inflammatory, and bactericidal properties. These properties suggest T. catigua bark extracts as a potential treatment for inflammatory bowel diseases (IBD). Using the 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced model of colitis in rats we evaluated the effect of an ethyl-acetate fraction (EAF) of T. catigua (200 mg/kg) administered by daily oral gavage or intrarectally at different time points after TNBS challenge. TNBS treatment evoked severe colonic inflammation after 24 h that persisted for 7 days, characterized by weight loss, high levels of myeloperoxidase activity, histological and macroscopic damage, and elevated index of oxidative stress in the blood. T. catigua EAF treatment prevented the oxidative stress within 24 h and enhanced tissue recovery observed at day 7, returning histological and macroscopic damage levels to that of the control group. TNBS treatment led to loss of myenteric neurons after 28 days. T. catigua EAF was unable to prevent the neuronal loss. Oral delivery of T. catigua EAF was more effective than intrarectal administration of the extract. In conclusion, T. catigua EAF treatment normalized oxidative stress parameters in blood and reduced the degree of acute inflammation in TNBS colitis.

Avaliação morfológica do cólon proximal de ratos diabéticos suplementados com extrato de Agaricus blazei murrill / Morphological evaluation of the proximal colon of diabetic rats supplemented with agaricus blazei murrill extract / Evaluación morfológica del colon proximal de ratas diabéticas suplementadas con extracto de agaricus blazei murrill

O diabetes mellitus tipo I é resultado da absoluta deficiência de insulina, estando associado à anormalidades no metabolismo. Transtornos no trato gastrointestinal, tais como vômitos, disfagia e diarreia são frequentes no diabetes, sendo relacionados a alterações na morfologia intestinal e no sistema nervoso entérico. Compostos ricos em antioxidantes vem sendo utilizados como prevenção ou tratamento do diabetes. Agaricus blazei Murrill possui grande interesse farmacológico pelas propriedades anti-inflamató- rias, hipoglicêmicas e antioxidantes. Neste trabalho, avaliamos a integridade estrutural da parede e inervação intrínseca do cólon proximal em modelo experimental de diabetes induzido por estreptozotocina, tratados ou não com A. blazei. Ratos Wistar foram dividi- dos em grupos: normoglicêmicos (N), diabéticos (D) e com suplementação (NB e DB) por gavagem do extrato hidroalcoólico de Agaricus blazei (200mg/Kg), por 120 dias. Amostras do cólon proximal foram destinadas à técnicas histológicas para análise mor- fométrica da túnica mucosa, profundidade das criptas, muscular da mucosa, muscular ex- terna e parede total, número de células caliciformes e avaliação morfoquantitativa da pop- ulação mioentérica. O diabetes promoveu redução da muscular externa e muscular da mucosa com aumento na profundidade das criptas e área nuclear neuronal. O extrato promoveu hipertrofia da mucosa e muscular da mucosa. Houve manutenção na espessura da parede total, número de células caliciformes e na população neuronal mioentérica no diabetes e na suplementação. Conclui-se que o diabetes induzido por estreptozotocina e a suplementação com o extrato de Agaricus blazei causam ajustes morfológicos nas túnicas intestinais, sem interferir na parede e inervação mioentérica do cólon proximal, preservando a morfofisiologia absortiva e motora deste segmento

Type I diabetes mellitus is a result of absolute insulin deficiency and is associated with abnormalities in metabolism. Disorders in the gastrointestinal tract, such as vomiting, dysphagia and diarrhea are common in diabetes, being related to changes in intestinal morphology and enteric nervous system. Antioxidant rich compounds have been used as prevention or treatment of diabetes. Agaricus blazei Murrill is highly pharmacologically interested in anti-inflammatory, hypoglycemic and antioxidant properties. In this work, we evaluated the structural integrity of the wall and intrinsic innervation of the proximal colon in an experimental model of streptozotocin-induced diabetes, treated or not with A. blazei Wistar rats were divided into groups: normoglycemic (N), diabetic (D) and supplementation (NB and DB) by gavage of the hydroalcoholic extract of Agaricus blazei (200mg / kg) for 120 days. Samples of the proximal colon were used for histological techniques for morphometric analysis of the mucosa, depth of the crypts, muscularis mucosa, external muscular and total wall, number of goblet cells and morpho-quantitative evaluation of the myenteric population. Diabetes promoted reduction of muscularis mucosa and external muscular with increased depth of the crypts and nuclear neuronal area. The extract promoted mucosa and muscular of the mucosa hypertrophy. There were maintenance of total wall thickness, number of goblet cells and in the myenteric neuronal population in diabetes and supplementation. It is concluded that streptozotocin-induced diabetes and supplementation with Agaricus blazei extract cause morphological adjustments in the intestinal tunica, without interfering with the wall and myenteric innervation of the proximal colon, preserving the absorptive and motor morphophysiology of this segment.

La diabetes mellitus tipo I es el resultado de la deficiencia absoluta de insulina y se asocia con anomalías en el metabolismo. Los trastornos del tracto gastrointestinal, como vómitos, disfagia y diarrea son frecuentes en la diabetes, estando relacionados con cambios en la morfología intestinal y en el sistema nervioso entérico. Los compuestos ricos en antioxidantes se han utilizado como prevención o tratamiento de la diabetes. Agaricus blazei Murrill está muy interesado farmacológicamente en propiedades antiinflamatorias, hipoglucémicas y antioxidantes. En este trabajo, se evaluó la integridad estructural de la pared e inervación intrínseca del colon proximal en un modelo experimental de diabetes inducida por estreptozotocina, tratada o no con ratas A. blazei Wistar, divididas en grupos: normoglucémico (N), diabético (D) y suplementación (NB y DB) por sonda del extracto hidroalcohólico de Agaricus blazei (200mg/kg) por 120 días. Se utilizaron muestras del colon proximal para técnicas histológicas de análisis morfométrico de la mucosa, profundidad de las criptas, mucosa muscular, pared externa muscular y total, número de células caliciformes y evaluación morfo-cuantitativa de la población mientérica. La diabetes promovió la reducción de la muscular de la mucosa y de la muscular externa con el aumento de la profundidad de las criptas y del área neuronal nuclear. El extracto promovió la hipertrofia mucosa y muscular de la mucosa. Hubo mantenimiento del espesor total de la pared, número de células caliciformes y en la población neuronal mientérica en diabetes y suplementación. Se concluye que la diabetes inducida por estreptozotocina y la suplementación con extracto de Agaricus blazei causan ajustes morfológicos en la túnica intestinal, sin interferir con la pared e inervación mientérica del colon proximal, conservando la morfofisiología absortiva y motora de este segmento.

Food restriction promotes damage reduction in rat models of type 2 diabetes mellitus.

There are several animal models of type 2 diabetes mellitus induction but the comparison between models is scarce. Food restriction generates benefits, such as reducing oxidative stress, but there are few studies on its effects on diabetes. The objective of this study is to evaluate the differences in physiological and biochemical parameters between diabetes models and their responses to food restriction. For this, 30 male Wistar rats were distributed in 3 groups (n = 10/group): control (C); diabetes with streptozotocin and cafeteria-style diet (DE); and diabetes with streptozotocin and nicotinamide (DN), all treated for two months (pre-food restriction period). Then, the 3 groups were subdivided into 6, generating the groups CC (control), CCR (control+food restriction), DEC (diabetic+standard diet), DER (diabetic+food restriction), DNC (diabetic+standard diet) and DNR (diabetic+food restriction), treated for an additional two months (food restriction period). The food restriction (FR) used was 50% of the average daily dietary intake of group C. Throughout the treatment, physiological and biochemical parameters were evaluated. At the end of the treatment, serum biochemical parameters, oxidative stress and insulin were evaluated. Both diabetic models produced hyperglycemia, polyphagia, polydipsia, insulin resistance, high fructosamine, hepatic damage and reduced insulin, although only DE presented human diabetes-like alterations, such as dyslipidemia and neuropathy symptoms. Both DEC and DNC diabetic groups presented higher levels of protein carbonyl groups associated to lower antioxidant capacity in the plasma. FR promoted improvement of glycemia in DNR, lipid profile in DER, and insulin resistance and hepatic damage in both diabetes models. FR also reduced the protein carbonyl groups of both DER and DNR diabetic groups, but the antioxidant capacity was improved only in the plasma of DER group. It is concluded that FR is beneficial for diabetes but should be used in conjunction with other therapies.

Cafeteria Diet Feeding in Young Rats Leads to Hepatic Steatosis and Increased Gluconeogenesis under Fatty Acids and Glucagon Influence.

Gluconeogenesis overstimulation due to hepatic insulin resistance is the best-known mechanism behind elevated glycemia in obese subjects with hepatic steatosis. This suggests that glucose production in fatty livers may differ from that of healthy livers, also in response to other gluconeogenic determinant factors, such as the type of substrate and modulators. Thus, the aim of this study was to investigate the effects of these factors on hepatic gluconeogenesis in cafeteria diet-induced obese adult rats submitted to a cafeteria diet at a young age. The livers of the cafeteria group exhibited higher gluconeogenesis rates when glycerol was the substrate, but lower rates were found when lactate and pyruvate were the substrates. Stearate or glucagon caused higher stimulations in gluconeogenesis in cafeteria group livers, irrespective of the gluconeogenic substrates. An increased mitochondrial NADH/NAD⁺ ratio and a reduced rate of 14CO2 production from [14C] fatty acids suggested restriction of the citric acid cycle. The higher glycogen and lipid levels were possibly the cause for the reduced cellular and vascular spaces found in cafeteria group livers, likely contributing to oxygen consumption restriction. In conclusion, specific substrates and gluconeogenic modulators contribute to a higher stimulation of gluconeogenesis in livers from the cafeteria group.

Maternal diet-induced obesity during suckling period programs offspring obese phenotype and hypothalamic leptin/insulin resistance.

During the early post-natal period, offspring are vulnerable to environmental insults, such as nutritional and hormonal changes, which increase risk to develop metabolic diseases later in life. Our aim was to understand whether maternal obesity during lactation programs offspring to metabolic syndrome and obese phenotype, in addition we aimed to assess the peripheral glucose metabolism and hypothalamic leptin/insulin signaling pathways. At delivery, female Wistar rats were randomly divided in two groups: Control group (CO), mothers fed a standard rodent chow (Nuvilab); and Diet-induced obesity group (DIO), mothers who had free access to a diet performed with 33% ground standard rodent chow, 33% sweetened condensed milk (Nestlé), 7% sucrose and 27% water. Maternal treatment was performed throughout suckling period. All offspring received standard rodent chow from weaning until 91-day-old. DIO dams presented increased total body fat and insulin resistance. Consequently, the breast milk from obese dams had altered composition. At 91-day-old, DIO offspring had overweight, hyperphagia and higher adiposity. Furthermore, DIO animals had hyperinsulinemia and insulin resistance, they also showed pancreatic islet hypertrophy and increased pancreatic ß-cell proliferation. Finally, DIO offspring showed low ObRb, JAK2, STAT-3, IRß, PI3K and Akt levels, suggesting leptin and insulin hypothalamic resistance, associated with increased of hypothalamic NPY level and decreased of POMC. Maternal obesity during lactation malprograms rat offspring to develop obesity that is associated with impairment of melanocortin system. Indeed, rat offspring displayed glucose dyshomeostasis and both peripheral and central insulin resistance.