Combination of cafeteria diet with intraperitoneally streptozotocin in rats. A type-2 diabetes model.

PURPOSE: To develop a model of induction of type-2 diabetes (DM2) by combining low doses of streptozotocin (STZ) and a cafeteria diet. METHODS: Forty male Wistar rats (200 g) were allocated into four groups: control (non-diabetic, n = 10); STZ 30 mg/kg (diabetic, n = 10); STZ 35 mg/kg (diabetic,n = 10); and STZ 40 mg/kg (diabetic, n = 10). DM2 was induced with a single intraperitoneal injection of STZ after four weeks of cafeteria diet in the three diabetic groups. All animals were evaluated as for anthropometric, and biochemical analyses, as well as liver, kidney and pancreas histological analyses. RESULTS: Lower weight gain, higher water intake, higher Lee index, hyperglycemia and modified total protein, urea, alpha-amylase, as well as insulin resistance, hepatic steatosis, pancreas, and kidney injury were observed in animals treated with 35 and 40 mg/kg of STZ. CONCLUSIONS: The results show that the experimental model using cafeteria diet associated with 35 mg/kg of STZ is a low-cost model and efficient in order to develop DM2, confirmed by the presence of polydipsia, hyperglycemia, altered biochemical tests, insulin resistance and damages to the liver, pancreas and kidney, which is similar to the disease found in humans.

Pro-inflammatory response induced by the venom of Parachartergus fraternus wasp.

The sting of different wasp species triggers local and systemic reactions in victims that can lead to death. Parachartergus fraternus is responsible for frequent accidents in Latin America; however, few studies have been conducted on this insect and its venom. In this study, the inflammatory process induced by the venom of the P. fraternus wasp (Pfv; 100, 200, and 400 µg/kg) was characterized. Mice were used to assess paw edema, vascular permeability, mast cell degranulation, leukocyte influx, nitric oxide (NO) production, expression of inflammatory genes, and histopathological changes. Pfv triggered edema formation with a peak dose of 200 µg/kg at 10 min. There was an increase in permeability in all periods and doses evaluated, with no differences between them. The 200 µg/kg dose induced mast cell degranulation in all periods, with a peak at 15 min. This same dose induced leukocyte influx with a predominance of mononuclear cells and triggered a peak in NO production in the 12th hour. The increase in COX-2, iNOS, and IFN-γ mRNA expression occurred after 1 and 6 h, and there was an increase in IL-10 expression after 48 h. In addition, Pfv triggered edema and induced an influx of macrophages and mast cells into the injection site. Therefore, Pfv induces an inflammatory process from the first 5 min of inoculation that can persist for up to 48 h.

Buriti pulp oil did not improve high-fat diet-induced metabolic disorders in c57bl/6 mice.

Metabolic syndrome (MetS) and obesity are growing in many parts of the world, becoming public health problems. It is proposed that foods with functional properties can assist in the treatment of these diseases. Crude buriti pulp oil (BPO) is a food traditionally consumed by residents in the Pantanal, Cerrado and Brazilian Amazon. It is rich in oleic acid, tocopherols and carotenoids, emerging as a potential functional food. Thus, this study aimed to evaluate the effect of the supplementation of BPO on metabolic disorders caused by a high-fat diet. Four groups of C57BL6 mice were used, a lean group with AIN-93M diet and control oil supplementation, an obese group with a high-fat diet and control oil supplementation, and two obese groups with a high-fat diet and BPO supplementation in the amounts of 50 and 100 mg/kg. BPO worsened the metabolic state caused by the high-fat diet, worsening risk factors associated with MetS, as the abdominal circumference and retroperitoneal fat, serum levels of total cholesterol, uric acid, alanine transaminase, glucose and triglycerides, and renal fat, in addition to changes in glycaemic control and oxidative stress markers. C57BL/6 mice fed with a high-fat diet and supplemented with BPO presented a worsening in metabolic risk factors associated with MetS.

Combination of cafeteria diet with intraperitoneally streptozotocin in rats. A type-2 diabetes model

ABSTRACT Purpose To develop a model of induction of type-2 diabetes (DM2) by combining low doses of streptozotocin (STZ) and a cafeteria diet. Methods Forty male Wistar rats (200 g) were allocated into four groups: control (non-diabetic, n = 10); STZ 30 mg/kg (diabetic, n = 10); STZ 35 mg/kg (diabetic,n = 10); and STZ 40 mg/kg (diabetic, n = 10). DM2 was induced with a single intraperitoneal injection of STZ after four weeks of cafeteria diet in the three diabetic groups. All animals were evaluated as for anthropometric, and biochemical analyses, as well as liver, kidney and pancreas histological analyses. Results Lower weight gain, higher water intake, higher Lee index, hyperglycemia and modified total protein, urea, alpha-amylase, as well as insulin resistance, hepatic steatosis, pancreas, and kidney injury were observed in animals treated with 35 and 40 mg/kg of STZ. Conclusions The results show that the experimental model using cafeteria diet associated with 35 mg/kg of STZ is a low-cost model and efficient in order to develop DM2, confirmed by the presence of polydipsia, hyperglycemia, altered biochemical tests, insulin resistance and damages to the liver, pancreas and kidney, which is similar to the disease found in humans.

Campomanesia sp. flour attenuates non-alcoholic fatty liver disease on rats fed with a hypercaloric diet.

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder caused by excess consumption of hypercaloric foods. Guavira (Campomanesia sp.) pulp has broad technological applicability, yet the peel and seeds are considered industrial residue. The objective of this unprecedented study was to evaluate the effects of the flour from guavira's industrial residue (GF) consumption in rats fed with hypercaloric diet (HD). During 65 days, 50 rats were separated into a control group: 1%, 2%, 4% and 8% HD with GF complementation in the diet. The GF chemical composition, phenolic compounds, antioxidant capacity, serum biochemical parameters (glucose, cholesterol, HDL, non-HDL, triglycerides, AST, ALT, and oral glucose tolerance test), fat liver content, and hepatic histomorphology had been characterized. GF is mainly composed of fibres, with phenolic content of 7,391.09 mg AGE/100 g GF and relevant antioxidant capacity (IC50 2.22 and ORAC 155.68 µmol/TE g-1 ). Serum biochemical analysis did not differ statistically (except ALT reduction, p < .05). Fat liver content was smaller on HD2%GF (p < .0001). The control group and 1% GF showed greater diffuse microvesicular steatosis compared to the other groups when using hepatic morphological analysis (p < .05). GF consumption attenuated NAFLD caused by a hypercaloric diet, and this effect may be related to the fibre content and bioactive compounds in GF.

Antitumor effect of depsidones from lichens on tumor cell lines and experimental murine melanoma

Abstract Lichens have exhibited numerous biological activities, including growth inhibition of tumor cells. This study evaluated the antiproliferative activity of hypostictic and salazinic acids against tumor cell lines (B16-F10, PC-03, MCF7, HT-29, HEP-G2, K562 and 786-0) by the SRB assay in vitro and antitumor activity in experimental murine melanoma in vivo. Activation of caspase-3 was quantified by flow cytometry. The murine experimental melanoma model B16-F10 was used in BALB/c mice for evaluation of antitumor activity. Hypostictic acid showed significant antiproliferative activity in K562 cells (GI50 2.20 µM), B16-F10 (GI50 13.78 µM) and 786-0 (GI50 14.24 µM), whereas salazinic acid was more active against K562 cells (GI50 64.36 µM), HT-29 (GI50 67.91 µM) and B16-F10 (GI5078.64 µM). Quantification of capase-3 revealed that the test compounds did not increase the expression of that enzyme. In the in vivo antitumor evaluation in B16-F10 melanoma, the isolated compounds inhibited tumor growth in relation to weight and volume. Hypostictic acid (16.7 mg/kg) inhibited 72% and salazinic acid 88% of tumor volume (p < 0.05). The results indicated that, both in the in vitro and in vivo models, the compounds evaluated showed antiproliferative and antitumor activities.

The Effects of Supplementing Hancornia speciosa (Mangaba) on Bowel Motility and Inflammatory Profile of Wistar Rats.

The prevalence of gastrointestinal disorders, such as constipation, has been increasing. Genetic factors and lifestyle are some of the etiologies of this issue, affecting the health of the population. Natural products have properties that contribute to health maintenance and health promotion, including reduction of the inflammatory process. Hancornia speciosa, popularly known as mangaba, is an abundant and native fruit in the Brazilian Cerrado, commercialized for culinary purposes and used because of its pharmacological properties. The objective of this study was to evaluate if the supplementation of different concentrations of mangaba pulp can improve intestinal motility and bowel health in Wistar rats. Forty male rats were divided into five groups. The experiment lasted 14 days and the groups were tested with water, industrialized laxative jelly made from tamarind as medication, or mangaba at 5, 10, and 15 mL/kg of body weight. Food intake, weight gain, ion balance, intestinal motility, and histopathological analysis of the small intestine, large intestine, and liver were evaluated. Supplementation of mangaba pulp at its highest concentration (15 mL/kg body weight) caused a 15% increase in the distance traveled by the charcoal meal, and a decrease in serum magnesium levels and white cells in both the small and large intestines. The results suggest that mangaba pulp presents laxative, anti-inflammatory properties and that its consumption is beneficial and should be encouraged.

Use of an Extract of Annona muricata Linn to Prevent High-Fat Diet Induced Metabolic Disorders in C57BL/6 Mice.

Annona muricata Linn, commonly known as graviola, is one of the most popular plants used in Brazil for weight loss. The aim of this study is to evaluate the therapeutic effects of three different doses (50 mg/kg, 100 mg/kg, and 150 mg/kg) of aqueous graviola leaf extract (AGE) supplemented by oral gavage, on obese C57BL/6 mice. Food intake, body weight, an oral glucose tolerance test (OGTT), an insulin sensitivity test, quantification of adipose tissue cytokines, weight of fat pads, and serum biochemical and histological analyses of the liver, pancreas, and epididymal adipose tissue were measured. AGE had an anti-inflammatory effect by increasing IL-10 at doses of 50 and 100 mg/kg. Regarding the cholesterol profile, there was a significant decrease in LDL-cholesterol levels in the AGE 150 group, and VLDL-cholesterol and triglycerides in the AGE 100 and 150 groups. There was an increase in HDL cholesterol in the AGE 150 group. The extract was able to reduce the adipocyte area of the epididymal adipose tissue in the AGE 100 and 150 groups. According to the histological analysis of the liver and pancreas, no significant difference was found among the groups. There were no significant effects of AGE on OGTT and serum fasting glucose concentration. However, the extract was effective in improving glucose tolerance in the AGE 150 group.

Tabebuia aurea decreases hyperalgesia and neuronal injury induced by snake venom.

ETHNOPHARMACOLOGICAL RELEVANCE: Tabebuia aurea (Silva Manso) Benth. & Hook. f. ex S. Moore is used as anti-inflammatory, analgesic and antiophidic in traditional medicine, though its pharmacological proprieties are still underexplored. In the bothropic envenoming, pain is a key symptom drove by an intense local inflammatory and neurotoxic event. The antivenom serum therapy is still the main treatment despite its poor local effects against pain and tissue injury. Furthermore, it is limited to ambulatorial niches, giving space for the search of new and more inclusive pharmacological approaches. AIM OF THE STUDY: evaluation of Tabebuia aurea hydroethanolic extract (HEETa) in hyperalgesia and neuronal injury induced by Bothrops mattogrossensis venom (VBm). MATERIALS AND METHODS: Stem barks from Tabebuia aurea were extracted with ethanol and water (7:3, v/v) to yield the extract HEETa. Then, HEETa was analyzed by LC-DAD-MS and its constituents were identified. Snake venoms were extracted from adult specimens of Bothrops mattogrossensis, lyophilized and kept at -20 °C until use. Male Swiss mice, weighting 20-25 g, were used to hyperalgesia (electronic von Frey), motor impairment (Rotarod test) and tissue injury evaluation (histopatology and ATF-3 immunohistochemistry). Therefore, three experimental groups were formed: VBm (1 pg, 1 ng, 0.3 µg, 1 µg, 3 and 6 µg/paw), HEETa orally (180, 540, 720, 810 or 1080 mg/kg; 10 mL/kg, 30 min prior VBm inoculation) and VBm neutralized (VBm: HEETa, 1:100 parts, respectively). In all set of experiments a control (saline group) was used. First, we made a dose-time-response course curve of VBm's induced hyperalgesia. Next, VBm maximum hyperalgesic dose was employed to perform HEETa orally dose-time-response course curve and analyses of VBm neutralized. Paw tissues for histopathology and DRGs were collected from animals inoculated with VBm maximum dose and treated with HEETa antihyperalgesic effective dose or neutralized VBm. Paws were extract two or 72 h after VBm inoculation and DRGs, in the maximum expected time expression of ATF-3 (72 h). RESULTS: From HEETa extract, glycosylated iridoids were identified, such as catalpol, minecoside, verminoside and specioside. VBm induced a time and dose dependent hyperalgesia with its highest effect seen with 3 µg/paw, 2 h after venom inoculation. HEETa effective dose (720 mg/kg) decreased significantly VBm induced hyperalgesia (3 µg/paw) with no motor impairment and signs of acute toxicity. HEETa antihyperalgesic action starts 1.5 h after VBm inoculation and lasted up until 2 h after VBm. Hyperalgesia wasn't reduced by VBm: HEETa neutralization. Histopathology revealed a large hemorragic field 2 h after VBm inoculation and an intense inflammatory infiltrate of polymorphonuclear cells at 72 h. Both HEETa orally and VBm: HEETa groups had a reduced inflammation at 72 h after VBm. Also, the venom significantly induced ATF-3 expression (35.37 ±â€¯3.25%) compared with saline group (4.18 ±â€¯0.68%) which was reduced in HEETa orally (25.87 ±â€¯2.57%) and VBm: HEETa (19.84 ±â€¯2.15%) groups. CONCLUSION: HEETa reduced the hyperalgesia and neuronal injury induced by VBm. These effects could be related to iridoid glycosides detected in HEETa and their intrinsic reported mechanism.