Safety Evaluation of Goat Milk Added with the Prebiotic Inulin Fermented with the Potentially Probiotic Native Culture Limosilactobacillus mucosae CNPC007 in Co-culture with Streptococcus thermophilus QGE: Analysis of Acute and Repeated Dose Oral Toxicity.

Despite functional goat milk products having emerged due to their importance for human nutrition and health, few studies have assessed the safety of consumption of goat dairy products containing potentially probiotic autochthonous lactic acid bacteria supplemented with prebiotic carbohydrates. Aiming this field, this study evaluated the safety of goat's milk fermented with Streptococcus thermophilus QGE, the autochthonous Limosilactobacillus mucosae CNPC007 culture, and the prebiotic inulin, through single- and repeated-dose oral toxicity tests (SDT and RDT, respectively) in animals. Ten female Swiss Webster mice were used for SDT evaluation - 2 groups, SDTc (20 mL/kg of filtered water) and SDTt (20 mL/kg of fermented milk) - and 40 Wistar rats for RDT - RDT3, RDT6, and RDT12 (treated with fermented milk at doses of 3 mL/kg, 6 mL/kg, and 12 mL/kg, respectively) and also RDTc (12 mL/kg of filtered water). For SDT, no signs of mortality or toxicity were observed, and the animals maintained the expected weight gain and feed intake. The RDT trials did not show mortality or signs of toxicity, as well as no change in body weight and organs, in the hematological and biochemical parameters, and also in relation to morphology and histology. Since the fermented milk did not cause any toxic effect in the conditions evaluated, it can be said that its no-adverse effect level (NOAEL) was considered to be higher than 20 mL/kg/day. Thus, the fermented milk with L. mucosae CNPC007 and inulin was considered to be of low toxicity, safe for use in rodents, and allowed for use in further studies.

Effect of semisolid formulation of persea americana mill (avocado) oil on wound healing in rats.

The aim of this study was to evaluate the wound-healing activity of a semisolid formulation of avocado oil, SSFAO 50%, or avocado oil in natura, on incisional and excisional cutaneous wound models in Wistar rats. An additional objective was to quantify the fatty acids present in avocado oil. On the 14th day, a significant increase was observed in percentage wound contraction and reepithelialization in the groups treated with 50% SSFAO or avocado oil compared to the petroleum jelly control. Anti-inflammatory activity, increase in density of collagen, and tensile strength were observed inSSFAO 50% or avocado oil groups, when compared to control groups. The analysis of the components of avocado oil by gas chromatography detected the majority presence of oleic fatty acid (47.20%), followed by palmitic (23.66%), linoleic (13.46%) docosadienoic (8.88%), palmitoleic (3.58%), linolenic (1.60%), eicosenoic (1.29%), and myristic acids (0.33%). Our results show that avocado oil is a rich source of oleic acid and contains essential fatty acids. When used in natura or in pharmaceutical formulations for topical use, avocado oil can promote increased collagen synthesis and decreased numbers of inflammatory cells during the wound-healing process and may thus be considered a new option for treating skin wounds.

Early undernutrition is associated with attenuated inflammatory response and alteration in pharmacological efficacy of indomethacin in rats.

AIM: The intent of this study is to examine whether intrauterine malnutrition provokes alterations in the progression of the acute and subchronic inflammatory response, and its influence on the pharmacological effect of indomethacin. METHODS DESIGN: Rat offspring of dams which were fed from the first day of their gestation to term receiving a balanced diet (Labina) or a basic regional diet (BRD) from northeastern Brazil. According to their dams, the offspring were divided in two groups: Control-N (nourished) and BRD-g (undernourished during gestation). At 2 months of age, the animals were divided into groups (n=06): (1) Animals that were subjected to carrageenan or (2) zymosan-induce paw edema (acute inflammation models) and (3) Animals that were subjected to cotton pellet-induced granuloma (subchronic inflammation model). All animals received (saline 0.9%; p.o.). Another set of adult offspring was submitted to the same procedure as above, but instead of saline they received (via gavage) a single oral dose of indomethacin (10mg/kg) for the animals subjected to acute inflammation models or 2mg/kg for seven consecutive days for the animals subjected to subchronic inflammation model. The animals were further divided in two groups: Control-NI (Control-N treated with indomethacin), and BRDI-g (BRD-g treated with indomethacin). The volume of hind paw swelling (mL) was measured at time zero (before), 30, 60, 120, 180 and 240 min after carrageenan or zymosan injection. In the subchronic model of inflammation, the pellets were removed and dried to a constant weight. Hind paw swelling, weight of granuloma, blood albumin and C-reactive protein (CRP) levels, leukocyte count and cytokine levels were evaluated as indicators of inflammation. RESULTS: Undernutrition during pregnancy caused fetal growth retardation which was shown in terms of low birth weight (5.38±0.28), when compared to the Control-N (7.26±0.64) group. The volume of paw edema, the serum levels of CRP and albumin and cytokine levels were lower than those in the BRD-g group when compared to those in the Control-N groups, in both models of acute inflammation studied. However, no difference was found in the total leukocyte count. When compared to the respective groups treated with saline (Control-N and BRD-g), the antiinflammatory effect of indomethacin in the animals of BRDI-g groups was lower than in the Control-NI groups, in the model of acute inflammation. In the model of subchronic inflammation, the pharmacological effect of indomethacin was effective only in nourished animals. CONCLUSION: Malnutrition in the early stages of development attenuated the severity of the acute inflammatory response, but there was no statistically significant change in subchronic inflammation induced by granulomatous lesion. Our findings provide impetus for larger trials to assess the influence of undernutrition on the pharmacokinetics/pharmacodynamics of indomethacin.

Effects of fetal programming in the inflammatory response in wistar rats: a systematic review / Efectos de la programación fetal en la respuesta inflamatoria en ratas wistar: una revisión sistemática

The aim of this study was to review the literature on the effects of fetal programming in the inflammatory response in Wistar rats. A search was performed in the following databases: PubMed, MEDLINE, PUBMED, SCIENCE DIRECT, SCOPUS, LILACS, SpringerLink. The main search terms were malnutrition and inflammation in Portuguese and in English. Original articles were included involving albino rats and review articles were excluded involving humans or animals other than rats. Articles that were related to malnutrition which was not intrauterine and did not involve the concept of fetal programming were also excluded. Those items found in more than one database were counted only once. Sixteen articles were found in PUBMED, 16 in SCOPUS, 4 in MEDLINE, 341 in SCIENCE DIRECT, 8 in SciELO, 1 in LILACS and 77 in SPRINGERLINK totalling 463 articles from which 4 were selected for analysis after applying inclusion and exclusion criteria. Fetal programming seems to interfere with the inflammatory response in the adult offspring of Wistar rats, but its mechanisms remain uncertain.

El objetivo de este trabajo fue revisar la literatura sobre los efectos de la programación fetal en la respuesta inflamatoria en ratas Wistar. Se realizó una búsqueda en las bases de datos: PubMed, MEDLINE, PUBMED, Science Direct, SCOPUS, LILACS, SpringerLink. Los términos principales de la búsqueda fueron la malnutrición y la inflamación y se buscaron en portugués e inglés. Se incluyeron artículos originales de ratas albinas y se excluyeron los artículos de revisión, las relacionadas con los seres humanos o animales, y de ratas en los artículos relacionados a la desnutrición, que no era el intrauterina y que no se referían al concepto de la programación fetal. Los artículos encontrados en más de una base de datos se contaron una sola vez. Encontramos 16 artículos en PUBMED, 16 en SCOPUS, 4 en MEDLINE, 341 en Science Direct, 8 SciELO, LILACS y 1 de cada 77 en SpringerLink, dando un total de 463 artículos. Después de la aplicación de la inclusión y exclusión de criterios fueron seleccionados 4 artículos para el análisis. La programación fetal parece interferir con la respuesta inflamatoria en los descendientes adultos de ratas Wistar, pero sus mecanismos siguen siendo inciertos.

Inibição dos efeitos da Peçonha de Bothrops Erythromelas (Jararaca-Malha-de-Cascavel) pelo extrato de Jatropha Molissima (POHL) Baill / Inhibition of Bothrops Erythromelas Venom effects by Jatropha Molissima (POHL) Baill extract

Objetivo: Comprovar a atividade inibitória do extrato hidroalcoólico do caule de Jatropha Molissima (EHA) sobre os efeitos mais relevantes da peçonha de Bothrops erythromelas (PBe). Material e Métodos: A peçonha liofilizada foi obtida da Fundação Ezequiel Dias (FUNED), Minas Gerais, Brasil. O extrato hidroalcoólico foi obtido do Laboratório de Produtos Naturais (UFPE), Recife, Pernambuco, Brasil. Foram usados camundongos, adultos, albinos Swiss pesando 25-30g. Várias concentrações do EHA foram incubadas, por 30 min. a 37°C, com doses fixas da PBe (2 doses mínimas), com exceção da permeabilidade vascular, na qual foi utilizada 0,05mg/Kg da PBe. O EHA nas doses de 50 a 400 mg/Kg, via intradérmica, não inibiu o aumento da permeabilidade vascular, pelo contrário, o mesmo potencializou o referido efeito. Por outro lado, a atividade hemorrágica da PBe, via intradérmica, foi parcialmente inibida nas doses de 20 a 160 mg/Kg e abolida com 320 mg/Kg. A atividade necrosante foi completamente inibida com 290,9 mg/Kg, e parcialmente inibida nas doses de 18,2 a 145,4 mg/Kg. A atividade defibrinogenante foi parcialmente inibida pelo EHA, via intravenosa, nas doses de 125 a 220 mg/Kg, enquanto com 285 mg/Kg foi abolida. Com relação à atividade coagulante da PBe, a mesma foi parcialmente inibida nas concentrações de 20,0 a 26,6 mg/ml e abolida com 29,2 mg/ml do EHA. Resultados: A atividade fosfolipásica foi parcialmente diminuída nas concentrações de 10,0 a 80,0 mg/ml, enquanto com 160 mg/ml foi abolida. Conclusão: Os resultados sugerem que o extrato de Jatropha molissima (POHL) Baill apresenta potencial para ser utilizado no tratamento de picadas de serpentes no Nordeste do Brasil.