Cyperus esculentus L. protects testis and sperm morphology of hyperglycaemic rats / Cyperus esculentus L. protege la morfología de los testículos y los espermatozoides de ratas hiperglicémicas

Cyperus esculentus L. (tiger nut) is a tuberous plant that promotes and protects reproductive functions, which are usually hampered in diabetics. The present study investigated the effect of Cyperus esculentus tuber extract (CETE) on testicular histology and sperm viability of alloxan-induced hyperglycaemic Wistar rats. Twenty-five adult male Wistar rats weighing 150-200g and grouped into five (n=5): Group 1, the control, administered tap water (20mL/kg), while groups 2-5 were administered a single intraperitoneal dose (120mg/kg b.w.) of alloxan, and each further received orally tap water (20mL/kg), CETE (100mg/kg), CETE (500 mg/kg) and metformin (500 mg/kg), respectively for 21 days. The animals were sacrificed, their sperm collected for analysis, while the testes were harvested, and processed for histology. Results showed significantly increased (p<0.05) blood glucose and testosterone, and significantly decreased (p<0.05) sperm pH, motility, count, morphology and density, as well as disruptions and hypertrophy of the spermatogenic and Sertoli cells of the hyperglycaemic group. There were significant (p<0.05) blood glucose decline, while the sperm parameters and testicular weight improved with normal testicular histology in the 100 mg/kg CETE, 500 mg/kg CETE, and metformin-treated groups compared to the control and hyperglycaemic group. Treatment with CETE showed blood glucose amelioration and improved sperm quality, as well as testicular damage attenuation.

Cyperus esculentus L. es una planta tuberosa que promueve y protege las funciones reproductivas, que generalmente se ven afectadas en los diabéticos. El presente estudio investigó el efecto del extracto de tubérculo de Cyperus esculentus (CETE) sobre la histología testicular y la viabilidad de los espermatozoides de ratas wistar con hiperglicemia inducida por alloxan. Veinticinco ratas Wistar macho adultas que pesaban 150-200 g y se agruparon en cinco (n = 5): el grupo 1, el control, administró agua del grifo (20ml / kg), mientras que los grupos 2-5 se les administró una dosis intraperitoneal única (120 mg / kg p.v.) de alloxan, y agua del grifo por vía oral (20ml/kg), CETE (100 mg/kg), CETE (500 mg/kg) y metformina (500 mg/kg), respectivamente durante 21 días. Los animales fueron sacrificados, su esperma recolectada para su análisis, mientras que los testículos fueron retirados y procesados para histología. Los resultados mostraron un aumento significativo (p<0,05) de la glucosa en sangre y la testosterona, y una disminución significativa (p<0,05) del pH, la motilidad, el recuento, la morfología y la densidad de los espermatozoides, así como interrupciones e hipertrofia de las células espermatogénicas y sertoli del grupo hiperglucémico. Hubo una disminución significativa (p<0,05) de la glucosa en sangre, mientras que los parámetros espermáticos y el peso testicular mejoraron con la histología testicular normal en los grupos de 100 mg / kg de CETE, 500 mg / kg de CETE y tratados con metformina en comparación con el grupo de control e hiperglucémico. El tratamiento con CETE mostró una mejora de la glucosa en sangre y una mejora de la calidad de los espermatozoides, así como atenuación del daño testicular.

Effect of Prosopis ruscifolia on incretin and insulin secretion in alloxan-induced hyperglycemic rats / Efecto de Prosopis ruscifolia sobre la secreción de incretina e insulina de ratas hiperglicémicas por aloxano

Background: Diabetes mellitus treatment is based on oral hypoglycemic agents or insulin. Medicinal plants constitute an option, and the leaves of Prosopis ruscifolia (Pr) were shown to be effective in reducing glycemia in hyperglycemic animals. Objective: In this paper, we report the effect of P. rusciofolia (Pr) on insulin and incretin secretion in alloxan-induced hyperglycemic rats. Methodology: The effective dose was selected, and four groups (n=10) of Wistar rats were used. Two groups with normal glycemia received water or Pr (75 mg/Kg, per os, p.o.), and two groups with hyperglycemia induced by alloxan (intraperitoneal, ip), received water or Pr (75 mg/Kg, p.o.) for 2 weeks. Oral glucose tolerance test, and incretin and insulin levels were measured at the end of the experimental period. Results: The results showed that extract promotes better tolerance to oral glucose overload, in addition to a statistically significant (p<0.001) increase in blood levels of incretin and insulin, compared to the hyperglycemic rats. Conclusion: It is concluded that the ethanolic extract of P. ruscifolialeaves has a hypoglycemic effect in hyperglycemic animals by a mechanism that involves the incretin-insulin system

Antecedentes: la diabetes mellitus es una enfermedad metabólica cuyo tratamiento se basa en el uso de agentes hipoglicemiantes orales o insulina. Una opción al tratamiento son las plantas medicinales y en ese sentido, estudios previos en animales con hojas de Prosopis ruscifolia (Pr) han demostrado efecto hipoglicemiante. Objetivo: en este trabajo se reporta el efecto de P. rusciofolia (Pr) en la secreción de insulina e incretina, en ratas hiperglicémicas por aloxano. Metodología: se emplearon cuatro grupos de ratas Wistar (n=10). Dos grupos con glicemia normal que fueron tratadas con agua Pr (75 mg/Kg, per os, p.o.) y dos grupos con hiperglicemia inducida por la inyección intraperitoneal de aloxano recibieron agua Pr (75 mg/Kg, per os, p.o.) durante dos semanas. Se midieron la tolerancia oral a la glucosa, y los niveles de incretina e insulina al final del periodo de experimentación. Resultados: se encontró que el extracto promueve una mayor tolerancia a la sobrecarga de glucosa, y además un incremento significativo (p<0.001) de los niveles de incretina e insulina en sangre, comparados al grupo de ratas hiperglicémicas. Conclusión: se concluye que e l estracto etanólico de las hojas de P. ruscifolia tienen efecto hipoglicemiante en animales hiperglicémicos por un mecanismo que incluye al sistema incretina-insulina

Efecto hipoglicemiante de Moringa oleifera (moringa) comparado con smallanthus sonchifolius (yacón) en Rattus norvegicus con diabetes mellitus inducida / Hypoglycemic effect of Moringa oleifera (moringa) compared with Smallanthus sonchifolius (yacon) on Rattus norvegicus with induced diabetes mellitus

RESUMEN Objetivo: Comparar el efecto hipoglicemiante del extracto acuoso de Moringa oleifera (moringa), Smallanthus sonchifolius (yacón) y metformina en Rattus norvegicus, variedad albina, con diabetes mellitus inducida. Materiales y métodos: Estudio preclínico, experimental controlado y aleatorizado. La diabetes se indujo por vía intraperitoneal con una dosis de aloxano a 130mg/kg de peso vivo (PV); se emplearon 24 Rattus norvegicus, variedad albina, machos, cepa Holfzman (seis por grupo). Se dividieron de la siguiente manera: grupo control (sin tratamiento), grupo metformina (14mg/kg PV), grupo M. oleifera (200mg/kg PV), y grupo S. sonchifolius (140 mg/kg PV), los tratamientos fueron administrados mediante sonda orogástrica durante 15 días. Los niveles de glicemia fueron determinados usando un glucómetro electrónico Accu-Chek® Instant (Roche). Resultados: Se observó reducción de la glicemia en los tratamientos: M. oleifera (p=0,009), S. sonchifolius (p=0,002) y metfotmina (p=0,002), en 313 mg/dL, 281,5 mg/dL y 415 mg/dL, respectivamente. En cuanto a la comparación de la glicemia en los grupos tratados y control, se observó que a las 24 horas y cuatro días de tratamiento no hubo diferencia (p>0,05); mientras que al octavo (p<0,05) y décimo quinto día (p<0,01) los grupos tratados tuvieron menor glicemia respecto al control, pero similares entre ellos. Conclusión: El extracto acuoso de S. sonchifolius y de M. oleifera, y la metformina presentaron similar efecto hipoglicemiante en ratas de experimentación con diabetes inducida.

ABSTRACT Objective: To compare the hypoglycemic effect of the aqueous extract of Moringa oleifera (moringa), Smallanthus sonchifolius (yacon) and metformin on Rattus norvegicus, albino variety, with induced diabetes mellitus. Materials and methods: Preclinical, experimental, controlled and randomized study. Diabetes was induced intraperitoneally with a dose of alloxan at 130 mg/kg. A total of 24 male Rattus norvegicus, albino variety, Holfzman strain (6 per group) were used. They were divided as follows: control group (no treatment), metformin group (14 mg/kg), M. oleifera group (200 mg/kg), and S. sonchifolius group (140 mg/kg), treatments were administered via orogastric tube for 15 days. Glycemia levels were determined using an Accu-Chek® Instant electronic glycometer (Roche). Results: Decreased glycemia was observed in the treatment groups: M. oleifera (p = 0.009), S. sonchifolius (p = 0.002) and metformin (p = 0.002), by 313 mg/dL, 281.5 mg/dL and 415 mg/dL, respectively. When comparing glycemia in the treated and control groups, no difference was observed (P > 0.05) at 24 hours and four days of treatment; while at the eighth (P < 0.05) and fifteenth day (P < 0.01) the treated groups had lower glycemia than the control group, but it was similar among them. Conclusion: The aqueous extract of S. sonchifolius, M. oleifera, and metformin presented similar hypoglycemic effect in experimental rats with induced diabetes.

Ethnopharmacological activity of Hedera nepalensis K. Koch extracts and lupeol against alloxan-induced type I diabetes

In this study, we investigated the protective effects of Hedera nepalensis crude extract, its fractions and lupeol in alloxan-induced diabetic rats. Lupeol and n-hexane (HNN) fraction significantly reduced the blood glucose level by increasing insulin level in time dependent manner, and also significantly increased amylase and lipase activity in diabetic rats. Elevated levels of alanine transaminases (ALT), aspartate transaminases (AST), thiobarbituric acid reactive substances (TBARS), nitrite, hydrogen peroxide (H2O2), total bilirubin and total protein in blood serum were efficiently restored to normal levels. Suppressed enzymatic activity of catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH) and peroxidase (POD) were also restored to their normal levels. Kidney functions were also restored to normal level after treatment with HNN and lupeol. HNN fraction and lupeol of H. nepalensis prevented oxidative stress in alloxan-induced diabetic rats. This study signifies the importance of H. nepalensis and lupeol in ameliorating diabetes by inducing insulin secretion in diabetic model rats.

Evaluación de los extractos de Amaranthus caudatus (Amaranto), Lupinus mutabilis (Tarwi) y Linum usitatissimum (Linaza), sobre la hiperglicemia inducida por aloxano en ratones / Evaluation of the extracts of Amaranthus caudatus (Amaranto), Lupinus mutabilis (Tarwi) and Linum usitatissimum (Linaza), on the Alloxane-induced hyperglycemia in mice

La prevalencia de diabetes mellitus se incrementa en todo el mundo alcanzando a 592 millones de diabéticos el año 2035; así mismo la OMS proyecta que las muertes por diabetes se dupliquen entre los años 2005 y 2030 (OMS, 2016). En Bolivia la medicina tradicional reporta plantas medicinales a las cuales se les ha atribuido propiedades hipoglucemiantes, sin embargo en muchos casos no existen estudios científicos que avalen dichas propiedades. Este estudio se ha realizado con la finalidad de evaluar el efecto de los granos de Amaranthus caudatus (amaranto), Linum usitatissimum (Linaza) y Lupinus mutabilis (tarwi) sobre la hiperglicemia inducida por aloxano en animales de experimentación. Se administró por vía oral a ratones con hiperglicemia (glicemia > 180,6 mg/dl) una dosis de 2000 mg/kg de peso corporal de cada extracto hidro-etanólico obtenido de los granos de A. caudatus, L. usitatissimum y L. mutabilis. Los niveles de glucosa fueron medidos antes y después de la administración de los extractos. Los extractos hidro-etanolicos disminuyeron de forma significativa (p<0.05) la glucosa plasmática a las cuatro y dos horas después de su administración. El extracto de A. caudatus disminuyo la glucosa plasmática de 380 mg/dl a 260 mg/dl, el extracto de L. mutabilis disminuyo la glucosa plasmática de 310 mg/dl a 167 mg/dl, y el extracto de L. usitatissimum disminuyo la glucosa plasmática de 210,57 mg/dl a 168,14 mg/dl. Siendo el extracto de L. mutabilis el que presento mayor actividad sobre la hiperglicemia inducida por aloxano.

The prevalence of diabetes mellitus increases worldwide reaching 592 million diabetics in 2035; Likewise, the WHO projects that deaths due to diabetes double between the years 2005 and 2030 (WHO, 2016). In Bolivia, traditional medicine reports medicinal plants to which hypoglycaemic properties have been attributed, however in many cases there are no scientific studies to support these properties. This study was carried out with the purpose of evaluating the effect of Amaranthus caudatus (amaranth), Linum usitatissimum (Linseed) and Lupinus mutabilis (tarwi) on the hyperglycemia induced by alloxan in experimental animals. Mice with hyperglycemia (glycemia>10 mmol/L) were administered a dose of 2000 mg/kg body weight orally of each hydro-ethanolic extract obtained from the grains of A. caudatus, L. usitatissimum and L. mutabilis. Glucose levels were measured before and after the administration of the extracts. The hydro-ethanol extracts significantly decreased (p <0.05) the plasma glucose at four and two hours after its administration. The extract of A. caudatus decreased the plasma glucose from 380 mg / dl to 260 mg / dl, the extract of L. mutabilis decreased the plasma glucose from 310 mg / dl to 167 mg / dl, and the extract of L. usitatissimum decreased Plasma glucose from 210.57 mg / dl to 168.14 mg / dl. The extract of L. mutabilis was the one with the highest activity on the hyperglycemia induced by alloxan.

Antidiabetic activity evaluation of Onobrychis species on alloxan-induced diabetic mice

In the current study, four Onobrychis species, O. albiflora Hub.-Mor., O. argyrea Boiss. subsp. argyrea Boiss., O. galegifolia Boiss., and O. tournefortii (Willd.) Desv. were collected from Anatolia to be evaluated for their antidiabetic activities. Methanol water extracts of the aerial parts were used for experiments. An alloxan-induced diabetic mice test model was used. Phytochemical analysis of the tested extracts was investigated using the HPLC method. The highest activity was observed with treatment of O. albiflora aerial part extract. Significant decrements were detected in the blood glucose levels as follows: 180.83±47.48 and 252.83±50.47mg/dL at 100 mg/kg and 200 mg/kg doses of O. albiflora, respectively, when compared to the isotonic saline solution control group, eliciting a blood glucose level of 494.20±27.32. Among the tested standard compounds, rutin and isoquercetin were detected in the examined species. The highest amount of rutin (1.1981±0.0017%) and isoquercetin (0.7318±0.0197%) were found in O. albiflora and O. argyrea subsp. argyrea, respectively. Antidiabetic activities of the tested Onobrychis species seem to indicate a possible correlation with their rutin and isoquercetin contents. Therefore, rutin and isoquercetin may be the antidiabetic compounds that contribute to the antidiabetic activity of the tested Onobrychis species.

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)

A insulina regula as vias de sinalização induzidas por LPS em macrófagos derivados de medula óssea / Insulin regulates LPS-induced signaling pathways in macrophages derived from bone marrow

Pacientes diabéticos apresentam alterações no sistema imunológico que promovem, em parte, maior suscetibilidade de infecções bacterianas. O tratamento com insulina melhora a sobrevida e reduz o número de infecções recidivas no paciente com diabetes mellitus do tipo 1 (DM1). Pouco se sabe sobre os efeitos do diabetes e a ação da insulina nos macrófagos. Neste trabalho, investigamos a proteína fosfatidilinositol-3-quinase (PI3K), proteína quinase B (Akt) e as quinases ativadas por mitógenos (MAPK) em macrófagos derivados de medula óssea (BMDM) e sua participação no estímulo por lipopolissacarídeo (LPS) na presença ou não do tratamento com insulina através da secreção dos mediadores inflamatórios fator de necrose tumoral (TNF)-α, interleucina (IL)-6 e IL-10. Observamos que os BMDM de animais com DM1 apresentam aumento da expressão da subunidade catalítica PI3K p110alpha com redução na subunidade reguladora PI3K p55 e maior expressão da fosforilação das proteínas Akt (Serina-473 e Treonina-308), quinase regulada por sinal extracelular (ERK) 1/2 e quinase ativada por estresse/quinase Jun-amino-terminal (SAPK/JNK) MAPK. Observou-se alteração na concentração das citocinas TNF-α, IL-6 e IL-10 no sobrenadante da cultura de BMDM dos animais diabéticos após estímulo com LPS, menor taxa de metabolismo mitocondrial, no entanto, sem resultar em morte celular, tampouco na expressão do receptor do tipo Toll 4 na membrana celular. Já o reestímulo destas células com LPS promoveu aumento na concentração de TNF-α sem alteração das demais citocinas. Além disto, o tratamento com insulina, simultaneamente ao estímulo com LPS, dos BMDM oriundos de animais diabéticos aumentou a concentração de TNF-α, IL-6, da fosforilação de p38, ERK 1/2 e SAPK/JNK MAPK, PI3K p55 e da Akt (Serina-473), o que não ocorreu nos BMDM dos animais não diabéticos sob a mesma condição. Este efeito foi abolido pela inibição farmacológica da PI3K e da ERK 1/2, resultando em novo aumento da concentração de TNF-α e IL-6. A análise conjunta destes resultados indica que a insulina, através da modulação das vias PI3K, Akt, ERK 1/2 e SAPK/JNK, amplifica o aumento da concentração de TNF-α e IL-6 sob estímulo com LPS

Diabetic patients present alterations in the immune system that promote in part a greater susceptibility of bacterial infections. Insulin treatment improves survival and reduces the number of recurrent infections in patients with type 1 diabetes mellitus (DM1). Little is known about the effects of diabetes and the action of insulin on macrophages. In this work we investigated the phosphatidylinositol-3-kinase (PI3K) / protein kinase B (Akt) and mitogen-activated kinase (MAPK) proteins in bone marrow-derived macrophages (BMDM) and their participation in lipopolysaccharide (LPS) or treatment with insulin through the secretion of inflammatory mediators tumor necrosis factor (TNF) -α, interleukin (IL) -6 and IL-10. We observed that BMDM of animals with DM1 increased PI3K p110alpha catalytic subunit expression with a reduction in the PI3K p55 regulatory subunit and increased expression of the phosphorylation of the Akt (Serine-473 and Threonine-308), extracellular signal regulated kinase (ERK) 1/2 and Jun-amino-terminal stress-kinase / kinase (SAPK / JNK) MAPK. Changes in the concentration of TNF-α, IL-6 and IL-10 cytokines in the supernatant of the BMDM culture of diabetic animals after stimulation with LPS were observed, possibly due to a lower rate of mitochondrial metabolism, however, without resulting in cell death , so little in the expression of the Toll 4 receptor on the cell membrane. The re-stimulation of these cells with LPS promoted an increase in TNF-α concentration without alteration of the other cytokines. In addition, insulin and simultaneously LPS stimulation of BMDM from diabetic animals increased the concentration of TNF-α, IL-6, phosphorylation of p38, ERK 1/2 and SAPK / JNK MAPK, PI3K p55 and Akt (Serine-473), which did not occur in the BMDM of non-diabetic animals under the same condition. This effect was abolished by pharmacological inhibition of PI3K and ERK 1/2, resulting in a further increase in the concentration of TNF-α and IL-6. The analysis of these results indicate that insulin by modulating the PI3K, Akt, ERK 1/2 and SAPK / JNK pathways amplifies the concentration levels of TNF-α and IL-6 under stimulation with LPS

Decreased mRNA Expression of Cystathionine Gamma lyase and H2S Concentration in Gastric Mucosal Tissue in Diabetic Rats

ABSTRACT Background and aim: It is well established that the rate of gastric lesions increases in diabetic rats. Recently, the protective effect of hydrogen sulfide (H2S) in gastric mucosa has been proven. This study aimed to determine the release of H2S and mRNA expression of cystathionine gamma lyase (CSE) in gastric mucosa in alloxan-diabetic rats in response to distention-induced gastric acid secretion. Twenty-four rats were randomly assigned to 4 groups (6 in each). They were the normal-control, distention-control, diabetic-control, and distention-diabetic groups. Under anesthesia, animals underwent a tracheotomy and midline laparotomy. To washout the gastric contents, a catheter was inserted in the stomach through the duodenum. To determine the effect of distention-induced gastric acid secretion on H2S release and mRNA expression of CSE, the stomachs were distended by normal saline. At the end of experiments, animals were sacrificed and the gastric mucosa was collected to determine H2S concentration and to quantify mRNA expression of CSE by quantitative real-time PCR. Mucosal release of H2S and mRNA expression of CSE significantly increased in response to stimulated gastric acid secretion in normal rats (P<0.01), while the increases in diabetic rats were not significant. Basal release of H2S and mRNA expression of CSE in gastric mucosa were significantly in diabetic rats lower than normal rats. On the basis of the results, we conclude that the decreased release of H2S in response to basal and stimulated gastric acid output in alloxan-diabetic rats compared to normal rats is largely due to downregulation of mRNA expression of CSE.

Effects of hyperbaric oxygen treatment on implant osseointegration in experimental diabetes mellitus

Abstract Objective To evaluate whether hyperbaric oxygen (HBO) treatment has a favorable effect on implant osseointegration in diabetic rabbits. Material and Methods An experimental diabetes model was induced in 32 New Zealand rabbits through IV injection of alloxan. After the state of diabetes had been confirmed, one dental implant was placed in the metaphysical region of each animal's tibia. After the implants' placements, the animals were divided into two groups. Half of the animals underwent HBO treatment, while the other group did not receive HBO treatment and served as the control group. The animals were euthanized at the 4th and 8th weeks. The osseointegration of the implants were compared by histomorphometry and resonance frequency analysis (RFA). Results The Bone Implant Contact (BIC) values were significantly higher in the HBO group than in the control group at the 4th week. There was no difference in the BIC values between the groups at the 8th week. There was no significant difference in the RFA scores between the groups both at the 4th and 8th weeks after the operation. Conclusion Histomorphometry findings suggest that HBO has positive effect on implant osseointegration in the early healing period in diabetic rabbits. However, implant stability is not affected by HBO treatment.

TNF-alpha expression, evaluation of collagen, and TUNEL of Matricaria recutita L. extract and triamcinolone on oral ulcer in diabetic rats

ABSTRACT Diabetes mellitus (DM) is a disease associated with delayed wound healing of oral ulcers by increased expression of proinflammatory cytokines and cellular apoptosis. Objective to evaluate the influence of Tumor Necrosis Factor alpha (TNF-α) and apoptosis in rats with DM treated with chamomile extract or triamcinolone. Material and Methods Wistar male rats (210.0±4.2 g) were divided into five groups: negative control group (NCG) without diabetes; positive control group (PCG) with DM (alloxan, 45 mg/kg); and groups treated with chamomile extract (normoglycemic= NCG group and diabetic= DCG group) and with triamcinolone (TG). Traumatic ulcers were performed on all animals that received topical triamcinolone, chamomile extract or saline 12/12 hours for ten days. Results On days five and ten the animals were euthanized and the ulcers were analyzed by light microscopy, TUNEL assay, and immunohistochemically (TNF-α). The NCG (p=0.0062), PCG (p=0.0285), NCG (p=0.0041), and DCG (p<0.0001) groups were completely healed on the 10th day, however, there was no healing on the TG (p=0.5127) group. The TNF-α expression showed a significant reduction from the 5th to the 10th day in NCG (p=0.0266) and DCG (p=0.0062). In connective tissue, the TUNEL assay showed a significant reduction in the number of positive cells in NCG (p=0.0273) and CNG (p=0.0469) and in the epithelium only in CDG (p=0.0320). Conclusions Chamomile extract can optimize the healing of traumatic oral ulcers in diabetic rats through the reduction of apoptosis in the epithelium and TNF-α expression.

Improvement of bone repair in diabetic rats subjected to ƛ780 nm low-level laser therapy

PURPOSE: To investigate the effect of low-level laser therapy on bone healing in diabetic rats.METHODS: Bone cavities (19 mm diameter) were performed in the femur of 72 alloxan-induced diabetic rats, which were assigned into four groups: CTR (non-diabetic control), DBT (diabetic) CTRL (non-diabetic irradiated) and DBTL (diabetic irradiated). Low-level laser therapy was performed every 48h for seven days. Animals were euthanized at seven, 18 and 30 days. Alkaline phosphatase serum levels and bone repair were analyzed.RESULTS: Low-level laser therapy significantly increased alkaline phosphatase in at seven and 18 days (p<0.001), and improved bone healing at seven (p<0.01), 18 (p<0.05) and 30 (p<0.01) in diabetic animals. In addition, bone healing in irradiated diabetic group was statistically similar to control group at 30 days (p>0.05).CONCLUSION:Low-level laser therapy increased the serum levels of alkaline phosphatase and improved bone healing in alloxan-induced diabetic rats.

Functional and biochemical characteristics of urinary bladder muscarinic receptors in long-term alloxan diabetic rats / Características funcionais e bioquímicas dos receptores muscarínicos da bexiga de ratos com diabetes crônico induzido por aloxana

Objective To re-examine the function of the urinary bladder in vivoas well as to determine the functional and biochemical characteristics of bladder muscarinic receptors in long-term alloxan-induced diabetes rats.Methods Two-month-old male Wistar rats were injected with alloxan and the animals showing blood glucose levels >300mg/dL together with age-paired untreated animals were kept for 11 months. Body weight, bladder weight, blood glucose, and urinary volume over a period of 24 hours were determined in both groups of animals. A voiding cystometry in conscious control and diabetic rats was performed to determine maximal micturition pressure, micturition contraction interval and duration as well as voided and post-voiding residual volume. In addition, concentration-response curves for bethanechol in isolated bladder strips, as well as [3H]-N methyl-scopolamine binding site characteristics in bladder homogenates were determined.Results Mean bladder weight was 162.5±21.2mg versus 290±37.9mg in control and treated animals, respectively (p<0.05). Micturition contraction amplitude (34.6±4.7mmHg versus 49.6±2.5mmHg), duration (14.5±1.7 seconds versus 23.33±4.6 seconds) and interval (87.5±17.02 seconds versus 281.11±20.24 seconds) were significantly greater in alloxan diabetic rats. Voided urine volume per micturition contraction was also significantly higher in diabetic animals. However the post-voiding residual volume was not statistically different. Bethanechol potency (EC50 3µM versus 5µM) and maximal effect (31.2±5.9g/g versus 36.1±6.8g/g) in isolated bladder strips as well as number (169±4fmol/mg versus 176±3fmol/mg protein) and affinity (0.69±0.1nM versus 0.57±0.1nM) of bladder muscarinic receptors were also not statistically different.Conclusion Bladder function in vivo is altered in chronic alloxan-induced diabetes rats without changes in functional and biochemical characteristics of bladder muscarinic receptors.

Objetivo Reestudar o funcionamento da bexiga in vivo e determinar as características funcionais e bioquímicas dos receptores muscarínicos vesicais de ratos com diabetes crônico induzido por aloxana.Métodos Ratos Wistar de dois meses de idade receberam injeção de aloxana, e os animais que apresentaram glicemia >300mg/dL foram mantidos por 11 meses junto de outros não tratados e pareados por idade. Nos dois grupos de animais, peso corpóreo, peso da bexiga, glicemia e volume urinário de 24 horas foram medidos. Em ambos os grupos, realizou-se a cistometria miccional em animais não anestesiados. Foram determinados os seguintes parâmetros: pressão máxima de micção, intervalo e contração de micção, bem como o volume de esvaziamento e o volume residual pós-miccional. Além disso, foram determinadas as curvas de concentração-resposta a betanecol em preparações isoladas de bexiga e também as características dos sítios de ligação da [3H]-N-metil-escopolamina em homogenatos de bexiga.Resultados O peso médio da bexiga foi de 162,5±21,2mg versus290±37,9mg nos animais controles e tratados, respectivamente (p<0,05). A amplitude de contração (34,6±4,7mmHg versus 49,6±2,5mmHg), a duração (14,5±1,7 segundos versus 23,33±4,6 segundos) e o intervalo (87,5±17,02 segundos versus 281,11±20,24 segundos) de micção foram significantemente maiores nos ratos tratados com aloxana. O volume de urina eliminada durante a contração miccional também foi maior nos animais diabéticos. Contudo, o volume residual pós-miccional não foi estatisticamente diferente. Não foram observadas diferenças na resposta ao betanecol (EC50 3µM versus 5µM) e no seu efeito máximo (31,2±5,9g/g versus 36,1±6,8g/g) em preparações isoladas de bexiga, bem como no número total (169±43fmol/mgversus 176±3fmol/mg) e na afinidade (0,69±0,1nMversus 0,57±0,1nM) dos receptores muscarínicos da bexiga.Conclusão O funcionamento da bexiga in vivo está alterado no diabetes crônico induzido por aloxana, porém sem alterações funcionais e bioquímicas nos receptores muscarínicos da bexiga.

Efecto hipoglicemiante de los extractos acuoso y etanólico de psidium guajava L. (Guayaba) en ratas diabéticas inducidas por aloxano / Hypoglycemic effect of aqueous and ethanol extracts of psidium guajava L. (guajava) in alloxan-induced diabetic rats

OBJETIVO: Evaluar la actividad antidiabética de los extractos acuoso y etanólico obtenidos a partir de las hojas de Psidium guajava L. en ratas diabéticas inducidas por aloxano. MAZTERIAL y METODOS: La hiperglicemia se indujo en ratas albinas mediante la administración de aloxano monohidrato (100 mg/kg ip). El extracto acuoso fue administrado en una sola dosis de 250 mg/kg, mientras que el extracto etanólico a las dosis de 250 y 500 mg/kg también a dosis única. La glucosa en sangre se determinó a las dos, cuatro y veinticuatro horas, después de la administración del aloxano. RESULTADOS: La administración de los extractos acuoso y etanólico de Psidium guajava L. tendieron a disminuir la concentración de glucosa en sangre. El extracto acuoso con una concentración de 250 mg/kg se encontró que era más potente que los extractos etanólicos, con la concentración de glucosa media más baja de 86,67 mg/dL, dos horas después de que se administró. El efecto del extracto etanólico sólo se observó en la concentración de 500 mg/kg con una ligera disminución de la glucosa en sangre. CONCLUSIÓN: Este estudio indicó una actividad antidiabética significativa del extracto acuoso de Psidium guajava L. en ratas diabéticas inducidas por aloxano.

OBJECTIVE: To evaluate antidiabetic activity of water and ethanol extracts from Psidium guajava L. leaves in alloxan-induced diabetic rats. MATERIAL and METHODS: Hyperglycemia was induced in albino rats by administering alloxan monohydrate (100 mg/kg i.p.). Water extract at a dose of 250 mg/kg was administered at a single dose, while ethanol extracts at doses of 250 and 500 mg/kg were also administered at a single dose. Blood glucose was determined two hours after administering the extracts. RESULTS: The addition of water and ethanol extracts of Psidium guajava L. tended to decrease the blood glucose concentration. The water extract at a concentration of 250 mg/kg was found to be more potent than ethanol extracts with the lowest mean glucose concentration of 86.67 mg/dL two hours after it was administered. The effect of ethanol extract was only observed at the concentration of 500 mg/kg with a slight decrease in blood glucose. CONCLUSION: This study indicated a significant antidiabetic activity of water extract of Psidium guajava L. in alloxan induced diabetic rats.

Diabetes mellitus experimental induzido com aloxana em ratos Wistar / Diabetes mellitus experimental by alloxan in Wistar rats

A indução do diabetes mellitus com substâncias citotóxicas como a Aloxana em animais de experimentação tem sido amplamente empregada com a finalidade de desenvolver estudos voltados ao tratamento desta patologia, mas alguns pesquisadores apontam dificuldades na indução e de manter os animais em bom estado geral de saúde por longos períodos. O objetivo do estudo foi rever protocolos de indução encontrados na literatura e contribuir com resultados de experiência própria destes autores neste procedimento, uma vez que a grande variedade de protocolos encontrada na literatura dificulta a escolha do pesquisador. Os resultados do estudo indicaram que as maiores dificuldades da indução estão relacionadas com a dose, via de administração, tempo de jejum na pré-indução e monitoramento dos animais pós-indução. Conclui-se que o monitoramento intensivo dos animais na primeira semana de indução, controle da hipoglicemia e hiperglicemia resulta em maior número de animais diabéticos e redução no índice de óbitos, tornando o procedimento da indução experimental mais eficiente.(AU)

The induction of diabetes mellitus with cytotoxic substances such as Alloxan in experimental animals has been widely employed for the purpose of developing studies related to the treatment of this pathology, but some researchers point out difficulties in inducing and maintaining animals in good general health by long periods. The aim of the study was to review induction protocols in the literature and contribute to results of these authors own experience in this procedure, since the wide variety of protocols found in the literature complicates the choice of the researcher. The study results indicated that the greatest difficulties are related to the induction dose, route of administration, duration of fasting pre - induction and post- induction monitoring of animals. We conclude that intensive monitoring of the animals in the first week of induction , the hypoglycemia and hyperglycemia results in greater number of diabetic animals and reduction in the rate of deaths , making the procedure more efficient experimental induction.(AU)

Urethral dysfunction due to alloxan-induced diabetes. Urodynamic and morphological evaluation

PURPOSE: To evaluate the effect of short and long term alloxan-induced diabetes on bladder and urethral function of female rats, and also describing its correlated morphological alterations. METHODS: Thirty five female rats were divided into three groups: G1 (n=9), control group; G2 (n=17), six weeks alloxan-induced diabetic rats; G3 (n=9), 20 weeks alloxan-induced diabetic rats. Functional evaluation was performed by cystometry and simultaneous measurements of the urethral pressure during bladder filling and voiding. Morphological evaluation was also performed with measurement of bladder and urethral fibrosis and collagen content and thickness of lamina propria and smooth muscle layers. RESULTS: The peak bladder pressures and contraction amplitudes were decreased in 100% and 47% of the G3 and G2 groups respectively, when compared to control. Bladder overactivity was observed in 53% of the G2 group. CONCLUSION: Alloxan-induced diabetes urethropathty in female rat was associated to bladder morphological alterations as higher thicknesses of it lamina propria, detrusor and adventicea. .

Protective effect of mulberry flavonoids on sciatic nerve in alloxan-induced diabetic rats

Mulberry leaves (Morus alba L.) are a traditional Chinese medicine for blood serum glucose reduction. This study evaluated the protective effects of mulberry flavonoids on sciatic nerve in alloxan-induced diabetic rats. In this study, 80 Sprague-Dawley rats were divided into five groups: A (control), B (diabetic treated with saline), C-D (diabetic treated with 0.3, 0.1 g/kg mulberry flavonoids once a day for 8 weeks) and E (diabetic treated with 0.3 mg/kg methycobal). The diabetic condition was induced by intraperitoneal injection of 200 mg/kg alloxan dissolved in saline. At the end of the experimental period, blood, and tissue samples were obtained for biochemical and histopathological investigation. Treatment with 0.3 g/kg mulberry flavonoids significantly inhibited the elevated serum glucose (P< 0.01). The increased myelin sheath area (P< 0.01), myelinated fiber cross-sectional area and extramedullary fiber number (P< 0.05) were also reduced in alloxan-induced rats treated with 0.3 g/kg mulberry flavonoids. 0.3 g/kg mulberry flavonoids also markedly decreased onion-bulb type myelin destruction and degenerative changes of mitochondria and Schwann cells. These findings demonstrate that mulberry flavonoids may improve the recovery of a severe peripheral nerve injury in alloxan-induced diabetic rats and is likely to be useful as a potential treatment on peripheral neuropathy (PN) in diabetic rats.

Folhas de amoreira (Morus alba L.) é um medicamento tradicional chinês para a redução da glicose no soro sanguíneo. Avaliaram-se, neste trabalho, os efeitos protetores dos flavonóides de amora no nervo ciático em ratos diabéticos aloxano-induzidos. Dividiram-se 80 ratos Sprague-Dawley em cinco grupos: A (controle), B (diabétidos tratados com solução salina), C-D (diabéticos tratados com 0,3, 0,1 g/kg) e E (diabéticos tratados com 0,3 mg de metilcobal).A diabetes foi induzida por injeção intraperitoneal de 200 mg/kg de aloxana dissolvida em solução salina. No final do período experimental, obtiveram-se amostras de sangue e de tecido para investigação bioquímica e histopatológica. O tratamento com 0,3 g/kg de flavonóides da amoreira inibiu, significativamente, a elevação de glicose no soro (p <0,01). O aumento da área da bainha de mielina (p <0,01), da área de fibra da seção transversal e do número de fibras mielinizadas extramedulares (p <0,05) foi também reduzido em ratos aloxânicos, tratados com 0,3 g/kg flavonóides de amora. Flavonóides da amoreira na dose de 0,3 g/kg também diminuiram, acentuadamente, a destruição da mielina do tipo bulbo de cebola e as alterações degenerativas das células mitocôndrias e das células de Schwann. Estes resultados demonstram que os flavonóides da amoreira podem melhorar a recuperação de uma lesão nervosa periférica grave em ratos com diabetes, induzida por aloxana, e parece ser útil como tratamento potencial para a neuropatia periférica (PN) em ratos diabéticos.

Zinc sulphate administered by transdermal iontophoresis improves breaking strength of surgical wounds in skin of alloxan-induced diabetic rats

PURPOSE:To investigate the effect of zinc sulphate administered by transdermal iontophoresis (TDI) on mechanical resistance of surgical wounds performed in the skin of diabetic rats. METHODS:One hundred and sixty male Wistar rats weighing approximately 250g were submitted to an incision surgery at the anterior region of abdomen and randomly distributed into four experimental groups with 40 non-diabetic control animals (G1) and 40 untreated diabetic animals (G2), both without any treatment of incisions; 40 non-diabetic animals (G3) and 40 untreated diabetic animals (G4), both with incisions treated with zinc sulphate, administered for a period of four consecutive days after surgery, in sessions of ten minutes duration, using a continuous-current electrostimulator (Zn + TDI). Each experimental group was further divided into four subgroups with ten rats each to be evaluated on the 4th, 7th, 14th, and 21st day after surgery. In each period were analyzed clinical and laboratory from the animals, and measured the breaking strength and hydroxyproline content (OH-P) of the skin scars. RESULTS: Breaking strength (BS) was significantly reduced (p<0.05) in skin scars of untreated diabetic rats (G2) on the 7th, 14th, and 21st postoperative days when compared to non-diabetic control rats (G1). In contrast, BS in skin scars of non-diabetic and untreated diabetic rats (G3, G4) treated with Zn + TDI showed significant increase (p<0.05) in those periods when compared with their respective controls with untreated incisions. The OH-P content of the scars did not show statistically significant variation in all studied groups at four different times evaluated after surgery. CONCLUSIONS: Zinc sulphate administered by transdermal iontophoresis had beneficial effect on the mechanical resistance of scars produced in the skin of diabetic rats. This therapeutic may have potential to reduce the complications observed in surgical wounds of the skin in diabetic subjects, mainly in most vulnerable stages of incisions to dehiscences, leakages and infections.