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)

Determination of the optimal diabetes duration for bone regeneration experiments in an alloxan-induced diabetic rabbit calvarial defect model

PURPOSE: The purpose of this study was to evaluate the optimal diabetes duration for bone regeneration experiments in an alloxan monohydrate (ALX)–induced diabetic rabbit calvarial defect model by evaluating the association between diabetes duration and bone healing capacity. METHODS: Twenty-four New Zealand white rabbits were used. Twenty-two rabbits were injected with 100 mg/kg of ALX to induce experimental diabetes. These rabbits were divided into 4 groups, including a control group and groups with diabetes durations of 1 week (group 1), 2 weeks (group 2), and 4 weeks (group 3). Calvarial defects were created at 1, 2, and 4 weeks after ALX injection and in the control rabbits. Cone-beam computed tomography (CBCT) scanning was performed on the day of surgery and at 2 and 4 weeks after surgery. The rabbits were sacrificed 4 weeks after surgery, followed by histological and immunofluorescence analysis. RESULTS: The diabetic state of all diabetic rabbits was well-maintained throughout the experiment. Reconstructed 3-dimensional CBCT imaging showed more rapid and prominent bone regeneration in the control group than in the experimental groups. Histological staining showed notable bone regeneration in the control group, in contrast to scarce bone formation in the experimental groups. The appearance and immunoreactivity of receptor activator of nuclear factor-kappa B and osteoprotegerin did not show notable differences among the groups. CONCLUSION: ALX administration at 100 mg/kg successfully induced experimental diabetes in rabbits. The effect of diabetes on bone healing was evident when the interval between diabetes induction and the intervention was ≥1 week.

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.

Evaluation of antidiabetic and antioxidant activity of aegle marmelos l. correa fruit extractdn the diabetic rats

Background: Diabetes mellitus is regarded as a serious chronic disease that carries a high risk for considerable complications

The use of natural plant products for management of diabetes is increasing due to their minimal side-effects and economical aspects. Aegle marmelos L. Correa [A. marmelos], family Rutaceae is highly reputed medicinal plant commonly known as bael. A. marmelos fruit is widely used in folk medicine for the treatment of diabetes mellitus

Aim of the work: This study was aimed to evaluate the antidiabetic and antioxidant activity of A. marmelos fruit ethanolic extract against alloxan-induced diabetes in male rats

Material and Methods: Twenty five male albino rats with an average body weight 180-195g were divided into two main groups; first group: control [n=5] and the second group: diabetic rats [n=20], which were divided equally to four subgroups as follows: diabetic untreated rats , diabetic rats which were treated with 125 mg/kg/day A. marmelos fruit extract; diabetic rats which were treated with 250 mg/kg/day A. marmelos fruit extract and diabetic rats treated with 500 mg/kg/day A. marmelos fruit extract. Diabetes was induced by a single intraperitonial injection of alloxan [120 mg/kg]

Results: Phytochemical screening of A. marmelos fruit extract revealed the presence of alkaloids, carbohydrates, glycosides, flavonoids, tannins, coumarins, sterols and triterpenoids. Results of the biological study reported that alloxan-induced diabetic group exhibited hyperglycemia, hyperlipidemia, elevation in malondialdehyde [MDA] level accompanied with weight loss and reduction in high density lipoprotein cholesterol [HDL-C] level, reduced glutathione [GSH] level and superoxide dismutase [SOD] enzyme activity when compared to control group. Treatment with A. marmelos fruit extract at the three dose levels reported improvement in the biological evaluation, lipid profile, glucose, insulin, MDA and GSH levels and SOD enzyme activity when compared to the diabetic group

The improvement was most pronounced in 500 mg/kg A.marmelos treated group.Conclusion: It could be concluded that A. marmelos fruit extract had hypoglycemic activity; this effect may be attributed to its antioxidant activity and its high content of active constituents which was proved in this study. Therefore, it could be recommended that A.marmelos fruit may be useful as a healthy food and in the development of antidiabetic drugs

Anti-diabetic and hypolipidemic effects of extract from the seed of Gossypium herbaceum L. in Alloxan-induced diabetic rabbits

Anti-diabetic and hypolipidemic effects of seed of Gossypium herbaceum L [GH] and its aqueous and ethanol extracts were investigated in alloxan-induced diabetic rabbits. Normal, Alloxan-induced diabetic and treated groups of rabbit were examined for their serum glucose, triglyceride, cholesterol, creatinine and urea levels. Water/food intake and toxic effect of test substances were also observed in treated rabbits. Effect of test agents on architecture of pancreatic beta-cells was evaluated histopathologically in rabbits. GH powder, its aqueous [GHA] and ethanol [GHE] extract significantly [P<0.05] reduced normoglycemia, serum cholesterol, triglyceride and urea in a dose dependent order [200-300 mg/kg of body weight] in normal rabbits. GH and GHE ameliorated completely the Alloxan effect on serum levels of glucose, cholesterol, triglyceride, creatinine and urea in Alloxan-induced diabetic rabbits. GHA and Glimepiride [a reference drug] partially blocked such effect of the Alloxan in treated rabbits. Further GH, GHA and GHE did not cause any change in food/water intakes and on liver, spleen, kidney, lung and heart in treated rabbits. Phytochemical study of GH and its extracts revealed the presence of flavonoids and phenolic compounds. Histopathological examination showed the protective effect of GH, GHA and GHE against Alloxan-induced destruction of beta-cells of pancreas in diabetic rabbits. Data indicated that GH and its aqueous and ethanol extracts have promising anti-diabetic and hypolipidemic effects. GH and GHE could be effective tool against the development, progression and complication of Diabetes mellitus

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.

biochemical effects of lime concentrate 'Aporo' and Mucuna pruriens seeds extract on Alloxan-induced diabetic rats

Objectives: This study evaluated the biochemical properties of a local lime concentrate preparation called Aporo and an ethanolic extract of seeds of Mucuna pruriens

Methods: Six groups of male Wistar rats, each containing five rats, were selected. Diabetes was induced in all rats, except the negative control group, by a single intraperitoneal injection of 150 mg/kg Alloxan. The induced rats, apart from the diabetic control group, were treated by daily oral administration of 5 mg/kg Glibenclamide, 100 mg/kg of Aporo decoction, an ethanolic extract of M. pruriens seed, and a combination of both in equal doses

Results: After 15 days of treatment, the blood glucose level of rats in the positive control group was found to be significantly lower than that of the other rats. However, Aporo extract exhibited a significantly higher ability to reduce blood glucose than the standard hypoglycaemic drug Glibenclamide. Aporo also increased high-density lipoprotein [HDL] levels and decreased triglyceride levels. The results showed that Aporo exhibited significant antioxidant, antidiabetic and antidyslipidaemic properties when used alone rather than in combination with Mucuna seed extracts

Conclusion: This study endorses the folk use of Aporo in the treatment of diabetes. However, further experimental studies are required to complement the results of the current study

Role of hypovitaminosis D in the incidence and complications of diabetes mellitus in rats

Background: Diabetes mellitus continues to be a public health concern. Vitamin D had sparked widespread interest in the pathogenesis and prevention of diabetes. The aim of this study was to investigate the effect of vitamin D [deficiency and treatment] with alteration in fasting plasma glucose, insulin resistance in alloxan injected rat

Materials and Methods: The experiment was carried out using 40 male albino rats [Sprague Dawley] weighing 150+/-10g. Animals were randomly divided into three groups; first group fed standard diet as a negative control group. Diabetic group injected subcutaneously by alloxan, and fed on standard diet. The third group fed standard diet without vitamin D for two weeks. After that glucose and insulin were determined in each rat of all groups to insure alteration in fasting plasma glucose, insulin resistance, Homeostasis model assessment insulin resistance [HOMA-IR] was calculated. Then the third group was divided to two subgroups. The first subgroup fed basil diet with required vitamin D; while the second subgroup fed standard diet with double dose vitamin D. At the end experiment [4 weeks], glucose, insulin, lipid profile, liver and renal functions were determined in blood and serum, while [HOMA-IR] and LDL were calculated for normal, diabetic group and both treatment subgroups

Results: Vitamin D deficiency group had the nearest results to the diabetic group injected with alloxan group in: insulin, glucose and HOMA-IR. Other groups had lower level than the other two groups in the same parameter. Our data explained the improvement in glucose level after feeding with vitamin D. Diabetic group injected with alloxan had increased in liver enzymes, renal function and lipid profile compared with other groups and showed variable changes in histopathological examination

Conclusion: Vitamin D deficiency status is associated with a higher risk of type 2 diabetes. Vitamin D improves glucose tolerance and insulin sensitivity. Vitamin D has also been shown to reduce the risk of diabetes associated complications

Influence of Musa sapientum L. on pharmacokinetic of metformin in diabetic gastroparesis / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of Musa sapientum L. (MS) bark juice in diabetic gastroparesis and its effect on pharmacokinetic of metformin (MET).</p><p><b>METHODS</b>Diabetes was induced in rats by administering alloxan (120 mg/kg) saline solution and maintained for 8 week. All the 18 Sprague-Dawley rats were divided into three groups (n =6 in each group): normal control, diabetic control and MS bark juice. Assessment of diabetes was done by glucose oxidase-peroxidase method on the 3rd day of alloxan administration. The effects of MS bark juice (100 mL/kg) on gastric emptying time, intestinal transit time, contractility of fundus and pylorus as well as gastric acid secretion in chronic diabetic rats were observed after 8 weeks of alloxan administration. The effect of MS bark juice on the pharmacokinetic of orally administered single dose of MET (350 mg/kg) was evaluated on the 57th day of protocol. Any drugs that may reduce the blood glucose level or influence the fibrinolytic system were not used in this study.</p><p><b>RESULTS</b>The MS bark juice significantly reduced the blood glucose level in the diabetic rats (P<0.01). There was significant decrease in the pylorus motility and increase in the gastric emptying time, intestinal transit time, contractility of fundus, gastric acid secretion in the MS bark juice treated group (P<0.01). There was significant decrease in the time at which drug at a maximum concentration, half life of drug and increase in the maximum concentration of drug in the plasma of MET in MS bark juice treated group as compared to diabetic control group (P<0.01).</p><p><b>CONCLUSION</b>MS bark juice effectively manages diabetic gastroparesis and thereby improves the bioavailabilty of MET when administered with MS bark juice.</p>

Similarities and differences between alpha-tocopherol and gamma-tocopherol in amelioration of inflammation, oxidative stress and pre-fibrosis in hyperglycemia induced acute kidney inflammation

BACKGROUND/OBJECTIVES: Diabetes mellitus (DM) is a major chronic disease which increases global health problems. Diabetes-induced renal damage is associated with inflammation and fibrosis. Alpha (AT) and gamma-tocopherols (GT) have shown antioxidant and anti-inflammatory effects in inflammation-mediated injuries. The primary aim of this study was to investigate effects of AT and GT supplementations on hyperglycemia induced acute kidney inflammation in alloxan induced diabetic mice with different levels of fasting blood glucose (FBG). MATERIALS/METHODS: Diabetes was induced by injection of alloxan monohydrate (150 mg/kg, i.p) in ICR mice (5.5-week-old, male) and mice were subdivided according to their FBG levels and treated with different diets for 2 weeks; CON: non-diabetic mice, m-DMC: diabetic control mice with mild FBG levels (250 mg/dl < or = FBG < or = 450 mg/dl), m-AT: m-DM mice fed AT supplementation (35 mg/kg diet), m-GT: m-DM mice with GT supplementation (35 mg/kg diet), s-DMC: diabetic control mice with severe FBG levels (450 mg/dl < FBG), s-AT: s-DM mice with AT supplementation, s-GT: s-DM mice with GT supplementation. RESULTS: Both AT and GT supplementations showed similar beneficial effects on NFkappaB associated inflammatory response (phosphorylated inhibitory kappa B-alpha, interleukin-1beta, C-reactive protein, monocyte chemotactic protein-1) and pre-fibrosis (tumor growth factor beta-1 and protein kinase C-II) as well as an antioxidant emzyme, heme oxygenase-1 (HO-1) in diabetic mice. On the other hands, AT and GT showed different beneficial effects on kidney weight, FBG, and oxidative stress associated makers (malondialdehyde, glutathione peroxidase, and catalase) except HO-1. In particular, GT significantly preserved kidney weight in m-DM and improved FBG levels in s-DM and malondialdehyde and catalase in m- and s-DM, while AT significantly attenuated FBG levels in m-DM and improved glutathione peroxidase in m- and s-DM. CONCLUSIONS: The results suggest that AT and GT with similarities and differences would be considered as beneficial nutrients to modulate hyperglycemia induced acute renal inflammation. Further research with careful approach is needed to confirm beneficial effects of tocopherols in diabetes with different FBG levels for clinical applications.

The effects of dosage and the routes of administrations of streptozotocin and alloxan on induction rate of type1 diabetes mellitus and mortality rate in rats / 한국실험동물학회지

The approach and novelty of this scientific work was to formulate the appropriate Streptozotocin (STZ) and Alloxan dosage in different routes of administration to imply minimum mortality rate and high incidence of diabetes mellitus (DM) in the rat experiment model. Rats were randomly divided into STZ, Alloxan and control groups. 1-Alloxan group was divided into two subgroups: intraperitoneal (ip) subgroups which received a single dose of, 140, 120, 100 and 80 mg/kg; and the subcutaneous (sc) subgroups which received a single dose of, 120, 110, 100, 90, and 80 mg/kg. 2-STZ group was divided into four subgroups of ip route. The ip subgroup which received intraperitoneally a single dose of, 30, 35, 40 and 50 mg/kg. 3-The control group: This group received solo distilled water. The injection day was considered as the day zero. Blood glucose levels and mortality rate were recorded. Subsequently, 30 days after, the logistic regression modeling was used to evaluate the effect of the explanatory variables, the dose levels, and route approaches, on the probability of DM incidence, and mortality. According to the statistical logistic analysis for Alloxan, it is concluded that the minimum dosage needed to induce DM was 120 mg/kg by sc method (probability 0.712). In addition, the logistic analysis for STZ showed that the optimal dose-level for STZ was 40 mg/kg with ip with approximate induction of DM probability 0.764. Based on the data, male Wistar rats in which received a single dosage of Alloxan by sc injection at dose of 120 mg/kg showed the most desirable result of induction of type I DM; furthermore, those in which received STZ by ip injection at the dose of 40 mg/kg developed a persistent and optimal DM state characterized by high rate of DM induction and low- level of mortality.

Establishment of An Alloxan-induced Diabetes Model in Daphnia Pulex / 中国医学科学院学报

Objective To establish a Daphnia model of alloxan-induced diabetes. Methods Daphnia were exposed to three different concentrations of alloxan (3, 5, and 10 mmol/L) for 30 minutes. Blood glucose and survival rate were recorded for 72 hours after alloxan insult. Sequence analysis and phylogenetic inference for glucose transporters (GLUT) were clustered with the maximum-likelihood method. Using reverse transcription and quantitative polymerase chain reaction techniques, we investigated the transcriptional changes of GLUT at 12 hours after alloxan (5 mmol/L) exposure. Results Compared with control, 3 mmol/L, and 5 mmol/L as well as 10 mmol/L alloxan initially induced transient blood glucose decline by 15% for 2 hours and 12 hours respectively. In Daphnia with 5 and 10 mmol/L alloxan, their blood glucose was persistently raised by about 150% since after 24-hour insult. Survival rate of Daphnia exposure to alloxan with concentrations of 3, 5, and 10 mmol/L were 90%, 75%, and 25% respectively. We predicted seven GLUT genes in the Daphnia genome and successfully amplified them using real-time polymerase chain reaction. Two of seven GLUT transcripts were down-regulated in Daphnia with 5 mmol/L alloxan-induced diabetes. Conclusion Alloxan-induced diabetes model was successfully established in the Daphnia pulex, suggesting diabetes-relevant experiments can be conducted using Daphnia.