Modelos murinos utilizados en la investigación de la Diabetes mellitus / Murine models used in research on Diabetes mellitus

La diabetes mellitus sobreviene cuando el páncreas produce una cantidad insuficiente de insulina o el cuerpo no utiliza de manera correcta esta hormona. Generalmente debido a su patogenia se clasifica en dos tipos: diabetes mellitus tipo 1 (insulino dependiente) y diabetes mellitus tipo 2. En los últimos años se ha convertido a nivel mundial en una de las principales causas de muerte y factor de riesgo para el desarrollo de diversas patologías. Debido a la implicancia en la salud humana y su cada vez mayor distribución a nivel mundial se ha convertido en uno de los tópicos de investigaciones de diversos grupos, quienes buscan comprender mejor su patogenia y desarrollar posibles tratamientos tanto a nivel molecular como celular. Las actuales técnicas de investigación desarrolladas abarcan modelos animales a los cuales se les induce esta patología químicamente, cepas de ratones que la desarrollan espontáneamente luego de cruces selectivos, y los creados por las más nuevas técnicas de ingeniería genética. A pesar de todo el esfuerzo no existe un único modelo que nos presente todo el abanico de posibilidades que se presentan en los seres humanos. Es por ello que se presentan diversos modelos con diferentes características, cada uno nos ayudará a comprender un poco más esta enfermedad.

Diabetes mellitus occurs when the pancreas produces an insufficient amount of insulin or the body does not use this hormone correctly. Generally, due to the pathogenesis, it is classified into two types: type 1 diabetes mellitus (insulin dependent) and type 2 diabetes mellitus. In recent years, it has become one of the main causes of death worldwide and a risk factor for the development of various pathologies. Due to the implication in human health and its increasing distribution worldwide, it has become one of the research topics of several groups, who are seeking to better understand diabetes pathogenesis and develop possible treatments both at the molecular and cellular level. The current research techniques developed include animal models in which this pathology is chemically induced, strains of mice that develop it spontaneously after selective crossing, and those created by the newest genetic engineering techniques. Despite all the effort, there is no single model that presents us with the full range of possibilities that occur in human beings. That is why various models with different characteristics are presented, each one will help us understand this disease a little more

Anxiolytic-like activity of Aloysia virgatavar. platyphylla leaves extract in mice / Actividad ansiolítica del extracto de hojas de Aloysia virgatavar. platyphylla en ratones

Background: Medicinal plants are part of traditional medicine and should be considered a therapeutic alternative for mental diseases. Several plants belonging to the Verbenaceae family have proved useful in treating general anxiety disorders, the most prevalent psychiatric disorders. Objective: This research aimed to verify the extract's safety, the effect on general behavior, and the effect on sleeping time, as well as to evaluate the anxiolytic-like effect of the methanol extract of Aloysia virgata var. platyphylla (Avp), in mice. Methodology: The toxicity test was done according to the OECD guide (mice groups n=5), and general behavior was observed during the assay. Sleeping time was assessed using the pentobarbital-induced hypnosis method (n=8). Male Swiss albino mice (n=6) were treated with 50 to 400 mg/kg of Avp extract and diazepam as a control. The anxiolytic-like effect was tested through the hole board and elevated plus-maze test. Results: The Avp extract has no side effects in tested doses, and no central nervous system depressant activity was noted. A. virgatavar. platyphyllaincreased exploration (number and time) in the hole board. In the elevated plus-maze, increased number and time into open arms were evidenced compared to the control group. Conclusion: With all these results, we concluded that the Avp extract is safe and has a potential anxiolytic-like activity in the animal model used

Antecedentes: Las plantas medicinales forman parte de la medicina tradicional y deben ser consideradas una alternativa terapéutica para las enfermedades mentales. Varias plantas pertenecientes a la familia Verbenaceae han demostrado su utilidad en el tratamiento de los trastornos de ansiedad, uno de los trastornos psiquiátricos más prevalentes. Objetivo: Esta investigación tuvo como objetivo verificar la seguridad del extracto, el efecto sobre el comportamiento general y el efecto sobre el tiempo de sueño, así como evaluar el efecto tipo ansiolítico del extracto metanólico de Aloysia virgata var. platyphylla(Avp), en ratones. Metodología: La prueba de toxicidad se realizó de acuerdo con la guía de la OCDE (grupos de ratones n=5), y se observó el comportamiento general durante el ensayo. El tiempo de sueño se evaluó mediante el método de hipnosis inducida por pentobarbital (n=8). Se trataron ratones albinos suizos macho (n=6) con 50 a 400 mg/kg de extracto de Avp y diazepam como control. El efecto ansiolítico se probó a través de la placa perforada y prueba del laberinto en cruz elevado. Resultados: El extracto de Avp no tiene efectos secundarios en las dosis probadas y no se observó actividad depresora del sistema nervioso central. A. virgata var. platyphylla aumentó la exploración (número y tiempo) en el tablero de agujeros. En el laberinto en cruz elevado, se evidenció un mayor número y tiempo en los brazos abiertos en comparación con el grupo de control. Conclusión: Con todos estos resultados, concluimos que el extracto de Avp es seguro y tiene una potencial actividad ansiolítica en el modelo animal utilizado

Preliminary evaluation of hepatoprotective and nephroprotective effects of Prosopis ruscifolia Griseb. leaves extract in mice

Liver and kidney are vital organs for body homeostasis and are exposed to damage or injury of various origins. Many medicinal plants have proved to be effective for hepatic and renal diseases. This study aimed to test the effect of Prosopis ruscifolia Griseb. leaves extract on acetaminophen-induced hepatotoxicity and gentamicin-induced nephrotoxicity. The experiment was carried out in mice, 300 mg/kg of acetaminophen, i.p., and 135 mg/kg of gentamicin were used to induce liver and kidney damage, respectively. Silymarin was used as protective control drug. For estimating the liver function, alkaline phosphatase (ALP), aspartate aminotransferase (AST or GOT), and alanine aminotransferase (ALT or GPT) were measured; and creatinine, urea, and uric acid were determined in order to verify kidney functionality. The results showed that the extract has both hepatoprotective and nephroprotective effect. This is evidenced by reduced values of the level of GOT, GPT, and ALP, in mice co-administered, p.o., with P. ruscifolia; and by the reduction of serum creatinine in mice with gentamicin induced kidney damage. These values showed statistically significant difference when compared with those of pathological group. The alcoholic extract of P. ruscifolia denoted hepatoprotective and nephroprotective effects.

Effect of Prosopis ruscifolia on lipid profile in alloxan-induced hyperglycemic mice and chemical characterization of alkaloid and flavonoid fractions

Diabetes mellitus interferes with the metabolism of carbohydrates, causing chronic hyperglycemia. Dyslipidemiain diabetes is a condition that leads to cardiovascular disease. This study was aimed to evaluate the effect of hydroalcoholic Prosopis ruscifolia (Pr) leaves extract on hyperglycemia and lipid profile in normo- and hyperglycemicmice. Mice hyperglycemia was induced by alloxan, animals were treated with Pr (50, 100, 200 mg/kg, p.o., 28 days).Fasted blood glucose level on days 7, 14, 21, and 28 was determined. Blood glucose remained within the normalrange in the groups of normoglycemic animals treated with Pr. In the hyperglycemic animals, 100 mg/kg of Pr extractreduced the glycemia, this effect became markedly evident since day 7, until the end of experimental period (p <0.0001), the total reduction reached was 60%. The lipid profile of normal and hyperglycemic mice was evaluated with100 mg/kg, on day 28. A non-significant increase in total cholesterol and low density cholesterol, in hyperglycemicanimals treated with vehicle, and a statistically significant increase (p < 0.0001) in the level of triglyceride and verylow density cholesterol (VLDL) level (p < 0.0001) in normoglycemic animals treated with Pr, compared to the controlgroup were denoted. This could indicate that Pr has a stimulating action on insulin secretion, since hyperinsulinemiais also associated with an increase in the quantity of atherogenic particles of VLDL cholesterol and triglycerides.The coronary risk index and the atherogenic index of hyperglycemic animals treated with Pr showed a reductioncompared with the untreated hyperglycemic ones. The presence of three piperidine alkaloids, juliprosopine, 3’’’’–Oxo-juliprosopine, and julifloridine, previously isolated from P. juliflora, was confirmed. Also, the presence of theflavonoid quercetin was detected in this plant. Those compounds are strong candidates presumably responsible forimparting the effect on glycemia and lipid profile reported here.

Efecto del consumo de alimentos con elevado contenido lipídico sobre el perfil lipídico de ratones sanos / Effect of the consumption of foods with high lipid content on lipid profile of healthy mice

La alteración de los lípidos en sangre o dislipidemias sobre todo el colesterol y triglicéridos, son un factor de riesgo de ateroesclerosis y enfermedades cardiovasculares. En este trabajo se analizó el efecto del consumo de huevo, clara, yema de huevo, mantequilla y maní sobre el perfil lipídico de ratones sanos. Se utilizaron seis grupos de ratones hembras sanas, el grupo control (GC) recibió balanceado comercial, mientras que en los demás grupos, 15% de su alimentación diaria consistió en huevo entero (GHE), yema (GY), clara de huevo (GCH), manteca o mantequilla (GMT) o maní (GMN), durante 28 días. Al final de este periodo, se obtuvo la muestra de suero para la determinación de los niveles de colesterol total (CT), triglicéridos (TG), colesterol HDL, colesterol LDL y colesterol VLDL, y se calcularon los índices de riesgo aterogénico y de riesgo cardiaco. Se observó un aumento estadísticamente significativo en los niveles de CT y LDL en relación al GC en los grupos GHE (p<0,0001), GY (p<0,0001), GCH (p<0,005) y GMT (p<0,001), mientras que en niveles de TG presentan un aumento los grupos GHE (p<0,0001) y GY (p<0,0001). El nivel de HDL aumentó significativamente en los grupos GHE (p<0,005) y GMT (p<0,001), y en cuanto al índice de riesgo cardiaco y aterogénico el grupo GY fue el único que reveló aumento significativo (p<0,0001). En el grupo que recibió maní (GMN), no se alteraron los niveles de lípidos, y por lo tanto tampoco el riesgo cardiaco ni aterogénico, lo que se traduce en un menor riesgo de enfermedades cardiovasculares de este grupo(AU)

The alteration of blood lipids or dyslipidemias, especially cholesterol and triglycerides, are a risk factor for atherosclerosis and cardiovascular diseases. In this work, the effect of consumption of egg, egg white, egg yolk, butter and peanut on the lipid profile of healthy mice was analyzed. Six groups of healthy female mice were used, the control group (GC) received commercial pellets, while for the other groups, 15% of their daily food consisted of whole egg (GHE), egg yolk (GY), egg white (GCH) ), butter (GMT) or peanut (GMN), for 28 days. At the end of this period, a serum sample was obtained for the determination of the levels of total cholesterol (CT), triglycerides (TG), HDL cholesterol, LDL cholesterol and VLDL cholesterol, and cardiac and atherogenic risk index were calculated. A statistically significant increase in TC and LDL levels was observed in relation to GC in the GHE (p <0,0001), GY (p <0,0001), GCH (p <0,005) and GMT (p <0,001) groups; whereas TG levels showed an increase in the GHE (p <0,0001) and GY (p <0,0001) groups. The HDL level increased significantly in the groups GHE (p <0,005) and GMT (p <0,001), and in terms of the cardiac and atherogenic risk index, the GY group was the only group that revealed a significant increase (p <0,0001). In the group that received peanuts (GMN), the lipid levels were not altered, and therefore neither the cardiac nor the atherogenic risk, which indicates the risk of cardiovascular diseases in this group, were affected(AU)

Efecto del consumo de pulpa de Carica papaya sobre la glicemia y peso de ratones normo e hiperglicémicos por aloxano / Effect of consumption of Carica papaya pulp on glycaemia and weight of normo and alloxan induced hyperglycemic mice

La Diabetes Mellitus se caracteriza por la menor capacidad del organismo de utilizar la glucosa, en la diabetes de tipo 2, la obesidad es el factor más relevante y más posible de prevenir. En este estudio se determinó el efecto del consumo de la pulpa de papaya o mamón (Carica papaya) sobre la glicemia y el peso corporal en ratones albinos suizos machos normo e hiperglicémicos inducidos por aloxano. Se organizaron cuatro grupos de seis ratones cada uno. Grupo I: normoglicémicos con dieta estándar, Grupo II: hiperglicémicos con dieta estándar, Grupo III: normoglicémicos con dieta estándar y papaya, Grupo IV: hiperglicémicos con dieta estándar y papaya, el experimento duró 28 días. Los valores obtenidos indican un descenso significativo en la glicemia de los animales del grupo hiperglicémico que fue alimentado con la pulpa de papaya (p<0,01), y también se observó una reducción estadísticamente significativa (p<0,001) en el peso corporal de los animales normoglicémicos que recibieron la pulpa de papaya. El consumo de C. papaya en los animales hiperglicémicos mejoró la glicemia, y produjo un impacto positivo en el metabolismo de la glucosa, y además disminuyó significativamente el peso corporal en los animales normoglicémicos(AU)

Diabetes Mellitus is characterized by the lower capacity of the body to use glucose, in type 2 diabetes, obesity is the most relevant environmental factor and most possible to prevent. In this study, the effect of the consumption of papaya pulp (Carica papaya) on glycaemia and body weight in male Swiss albino mice and hyperglycemic mice induced by alloxan was determined. Four groups of six mice each were organized. Group I: normoglycemic with standard diet, Group II: hyperglycemic with standard diet, Group III: normoglycemic with standard diet and papaya, Group IV: hyperglycemic with standard diet and papaya, the experiment lasted 28 days. The results showed a significant decrease in the glycaemia of animals in hyperglycemic group that was fed with the papaya pulp (p <0.01), and also a statistically significant reduction (p <0.001) in the body weight in normoglycemic mice fed with standard diet and papaya. The consumption of C. papaya in hyperglycemic animals improved the glycaemia, and positively impacted in glucose metabolism, additionally induced a significant reduction on the body weight of normoglycemic animals(AU)

Evaluación del efecto de Aloe barbadensis sobre el peso en ratones normopesos y obesos / Evaluation of the effect of Aloe barbadensis on weight in normal and obese mice

La obesidad es el trastorno metabólico más frecuente, para el tratamiento es fundamental el cambio del tipo alimentación y mantener un estilo de vida saludable. La publicidad engañosa sobre productos denominados milagrosos conlleva a un consumo desmedido, no controlado y sin previa evaluación de los resultados sobre el peso y/o la posible toxicidad de los mismos. Se diseñó una investigación preliminar en ratones, para verificar el efecto del zumo de Aloe barbadensis y un producto comercial sobre el peso de ratones normopesos y obesos inducidos por glutamato monosódico (GMS), después de cuatro semanas de tratamiento. El grupo de ratones inducidos a obesidad con GMS, presentaron un porcentaje de cambio de peso de 160,5±37,5%, mientras que en el grupo de ratones normopesos fue de 59,4±12,1%, esta diferencia resultó significativa (p<0,001). En los ratones obesos que recibieron el zumo de A.barbadensis se logró un descenso no significativo de peso de 2,8% con respecto al peso al inicio de la intervención (p 0,05). En los ratones obesos tratados con el producto comercial se observó un aumento de peso, aunque en menor proporción que los obesos que recibieron agua (3,5% y 4,4%, respectivamente). Los resultados indican que el zumo de Aloe barbadensis induce un descenso de peso mayor en los animales obesos, comparado con el producto comercial, sin embargo, esto no es significativo en el periodo de observación. Palabras claves: Aloe barbadensis, peso corporal, obesidad, glutamato monosódico, ratón.

Obesity is the most frequent metabolic disorder, for the treatment is fundamental to change the type of food and maintain a healthy lifestyle. Misleading advertising of so-called miraculous products leads to excessive, uncontrolled consumption and without prior evaluation of the effect on weight or their possible toxicity. A preliminary investigation was designed in mice, to verify the effect of the juice of Aloe barbadensis and a commercial product on the weight of normal and obesemice induced by monosodium glutamate(MSG),after four weeks of treatment. The group of mice induced to obesity with MSG had a weight change percentage of 160.5 ± 37.5%, while in the group with normal body weight was of 59.4 ± 12.1%, this difference was significant (p<0,001). In the obese mice that received the juice of A. barbadensis, a non-significant weight decrease of 2.8% was achieved when compared with the weight at the beginning of the intervention (p0.05). In obese mice treated with the commercial product,an increase in weight was observed, although in a smaller proportion than the obese ones that received water (3.5% and 4.4%, respectively). The results indicated that Aloe barbadensis juice induced a greater weight loss in obese animals, compared to the commercial product, however, this is not significant in the period considered. Key words: Aloe barbadensis, body weight, obesity, monosodic glutamate, mice.

Influencia del consumo de pulpa de aguacate,Persea americana, sobre el metabolismo lipídico en ratones normolipémicos e hiperlipémicos inducidos por dieta / Influence of avocado (persea americana) pulp consumption on lipid metabolism in normolipidemic and diet induced hyperlipidemic mice

La dislipidemia es un factor de riesgo para el desarrollo de enfermedades cardiovasculares, una de las principales causas de muertes a nivel mundial. En este trabajo se estudió el efecto del aguacate (Persea americana) sobre el metabolismo lipídico de ratones normo e hiperlipémicos inducidos con dieta hiperlipídica. Ratones machos, fueron distribuidos en 4 grupos DE (dieta estándar), DEa (dieta estándar y aguacate); DH (dieta hiperlipídica) y DHa (dieta hiperlipídica y aguacate) y observados por 28 días. Luego de este periodo se determinaron los niveles de Colesterol Total, Triglicéridos y col-HDL y se calcularon los valores de col-LDL, VLDL e índices de riesgo aterogénico y de riesgo coronario. El grupo DH mostró niveles de CT, TG, col-LDLy VLDL significativamente superiores (p<0,001) a los valores alcanzados en el grupo DE. En los grupos DHa y DEa se redujeron significativamente (p<0,001) las concentraciones de CT, TG, col-LDL y VLDL, en comparación al grupo DH. Los grupos DEa y DHa difieren significativamente (p<0,005) en el nivel de CT, éste último presenta valores más bajos, los otros parámetros cuantificados no mostraron diferencias significativas. No hubo diferencias significativas para los valores del col-HDL en ningún grupo de estudio. La inducción a la hiperlipemia con un modelo de dieta hiperlipídica, generó incrementos importantes en el CT, TG, col-LDL y VLDL, además de aumentar el riesgo aterogénico. El consumo de la pulpa de aguacate redujo los niveles de CT, TG, col-LDL, VLDL y el índice de riesgo aterogénico en el grupo de ratones hiperlipémicos(AU)

Influence of avocado (Persea americana) pulp consumption on lipid metabolism in normolipidemic and diet induced hyperlipidemic mice . Dyslipidemia is a risk factor for developing cardiovascular disease, a major cause of deaths worldwide. The aim of this work is to study the effect of avocado (Persea americana), on lipid metabolism on normolipidemic and hyperlipidemic mice induced with high fat diet. Four groups of animals receiving standard diet (DE), standard and avocado diet (DEa), high fat diet (DH) and high fat and avocado diet (DHA) were used. All animals were observed for a period of 28 days. Blood sample was obtained at the end of experimentation period by cardiac puncture on anesthetized animals, and the levels of Cholesterol, triglycerides and col-HDL were de- termined and c-LDL, VLDL and atherogenic and coronary risk factors were calculated. DH group showed levels of TC, TG, c-LDL and VLDL significantly higher (p<0,001) than the values achieved in DHa group. DHa and DEa plasmatic values of TC, TG, c-LDL and VLDL were significantly reduced (p <0.001) compared to DH group. DEa and DHA groups differed significantly (p <0.005) in the level of CT, the latter has lower values, the other quantified parameters showed no significant differences. There were no significant differences for c-HDL values in any group. Hyperlipidemia induction with a model of high fat diet produced significantly increasing values of TC, TG, c-LDL and VLDL, besides of increasing the atherogenic risk. The benefit of avocado pulp consists in reduction of TC, TG, c-LDL, VLDL and the index of atherogenic risk(AU)

Acute and Chronic anti-hyperglycemic effect of Prosopis ruscifolia extract in Normoglycemic and Alloxan-Induced Hyperglycemic Rats.

Prosopis ruscifolia, vinal, is used to treat diabetes. This work aims to study the influence of the hydro-alcoholic extract of this plant on alloxan induced diabetic rats. Hydroalcoholic extract from aerial parts of Prosopis ruscifolia Griseb. (Fabaceae) was prepared (Pr) and the safety was assessed to determine the acute toxicity in mice. The hypoglycemic activity of the extract was evaluated in normo- and hyperglycemic rats. Hyperglycemia was induced by intravenous administration of alloxan monohydrate (32 mg/Kg body weight). Rats with blood glucose level higher than 200 mg/dL were used for the experiment. The animals were assigned to different groups and treated with a single dose of solvent (water, p.o.), Pr (100 mg/Kg, p.o.), tolbutamide (100 mg/Kg, p.o.) or insulin (5 IU/kg, i.p.); Pr extract was also administered to normoglycemic rats (100 mg/kg, p.o.). Fasted blood glucose level was measured at times 0, 1, 2, 4 and 24 h after treatment, in the acute test, and at days 0, 14, 21 and 28, in the chronic study. No evidence of acute toxicity in mice was observed. The results show that Pr extract significantly reduces blood glucose level in hyperglycemic rats (p < 0.01) 24 h after administration of a single oral dose of 100 mg/Kg. Treatment with Pr during 28 days showed a reduction in blood glucose level in experimentally hyperglycemic rats. Additionally, rats treated with the extract showed a reduced body weight gain. Prosopis ruscifolia hydroalcoholic extract showed low toxicity. After acute and chronic oral treatment was effective to reduce fasted blood glucose level, and the body weight gain was less after 28 days in the treated group.

Anxiolytic-like and sedative effects of Kyllinga brevifolia in mice

Kyllinga brevifolia Rottb., Cyperaceae, rhizomes have been widely used in the Paraguayan folk medicine as digestive, diuretic, sedative, tonic, antispasmodic and sudorific. The purpose of this study is to characterize the putative sedative, anxiolytic effects of the crude hydro-ethanolic extract (CEKb) and fractions of the rhizome of K. brevifolia, in male mice. The behaviour of mice was assessed in the open field, hole board, rota-rod and elevated plus-maze (EPM) test. Oral treatment with single doses of 10, 100 and 1000 mg/kg of CEKb and 10 mg/kg of ethyl acetate fraction (KbF-ethyl-ac) increased the duration of the sleeping time induced by pentobarbital. Oral administration of 1, 10 and 100 mg/kg of CEKb and 0.1, 1 and 10 mg/kg of KbF-ethyl-ac also significantly increased the time-spent and arm entries into open arms of the elevated plus maze (EPM) versus control group. These findings indicate that K. brevifolia exerts a weak sedative and an interesting anxiolytic-like effect in mice and suggest its potential usefulness for the treatment of anxiety in humans.

Phytochemical profile of the stems of Aeonium lindleyi

Aeonium species are plants rich in phenols and terpenoids and have been widely used in the Canary folk medicine. Following our project concerning bioactive compounds from Macaronesian region, a phytochemical study was carried out to investigate the constituents of the stems of Aeonium lindleyi Webb & Berthel.,Crassulaceae. Air dried and chopped stems of this plant were extracted with ethanol in a Soxhlet apparatus and the total extract was chromatographed on silica gel to afford sixteen known compounds including, one sterol, four lupane triterpenes and eleven phenolic compounds. Their structures were elucidated by means of ¹H- and 13C-NMR spectroscopic studies and comparison of their spectral data with values in the literature. Both group of isolated metabolites are known by their diverse biological activities and they have been described as antioxidant, cytotoxic, anti-inflammatory. Our results contribute to the knowledge of A. lindleyi as a potential source of bioactive compounds.