Combined administration of gallic acid and glibenclamide mitigate systemic complication and histological changes in the cornea of diabetic rats induced with streptozotocin

Purpose: To determine the effect of gallic acid or its combination with glibenclamide on some biochemical markers and histology of the cornea of streptozotocin (STZ) induced diabetic rats. Methods: Following induction of diabetes, 24 male albino rats were divided into four groups of six rats each. Groups 1 and 2 (control and diabetic) received rat pellets and distilled water; group 3 (gallic acid) received rat pellets and gallic acid (10 mg/kg, orally) dissolved in the distilled water; and group 4 (gallic acid + glibenclamide) received rat pellets, gallic acid (10 mg/kg, orally), and glibenclamide (5 mg/kg, orally) dissolved in the distilled water. The treatments were administered for three months after which the rats were sacrificed after an overnight fast. Blood and sera were collected for the determination of biochemical parameters, while their eyes were excised for histology. Results: STZ administration to the rats induced insulin resistance, hyperglycemia, microprotenuria, loss of weight, oxidative stress, inflammation, and alteration of their cornea histology, which was abolished following supplementation with gallic acid or its combination with glibenclamide. Conclusions: The study showed the potentials of gallic acid and glibenclamide in mitigating systemic complication and histological changes in the cornea of diabetic rats induced with STZ.

Efectos de la inyección neonatal de estreptozotocina sobre indicadores bioquímicos y de estrés oxidativo en ratas / Effects of neonatal injection of streptozotocin on biochemical indicators and oxidative stress in rats

Introducción: Debido a sus propiedades químicas, la estreptozotocina es uno de los agentes diabetogénicos más utilizados para generar modelos biológicos de diabetes, por lo que es necesario estudiar cuáles son sus efectos en el organismo del animal de laboratorio. Objetivo: Evaluar, en un periodo de 90 días, los efectos de la inyección neonatal de estreptozotocina en ratas Wistar sobre indicadores bioquímicos y de estrés oxidativo en hígado y riñón. Métodos: La diabetes fue inducida neonatalmente por 100 mg de estreptozotocina en ratas Wistar. Se realizaron determinaciones de glucemia, insulina e indicadores de estrés oxidativos en hígado y riñón en cinco animales por grupo a los días 5, 10, 20, 30, 60, 90 de nacidos. Resultados: En todas las intervenciones, la glucemia e insulina mostraron diferencias significativas en el grupo-STZ respecto al control. El valor máximo de hiperglucemia se observó al quinto día. La concentración de nitratos y nitritos en hígado fue mayor que en riñón. En comparación con el grupo control, en el tejido hepático del grupo-STZ la concentración de nitratos y nitritos resultó significativamente superior los días 10-20. En todas las intervenciones se detectó consumo de glutatión reducido en ambos órganos. En el hígado de las ratas STZ no se demostró daño a lípidos ni proteínas; sin embargo, en riñón se detectó daño significativo en ambas biomoléculas al quinto día. Conclusiones: Tanto la citotoxicidad de la estreptozotocina neonatal como las concentraciones de glucosa e insulina inducidas repercutieron negativamente sobre los indicadores de estrés oxidativo estudiados en tejido hepático y renal(AU)

Introduction: Streptozotocin is currently one of the most used diabetogenic agents to generate biological models of diabetes due to its chemical properties, so it is necessary to study the consequences of STZ for the organism of the laboratory animal. Objective: To evaluate in a period of 90 days the effects of neonatal injection of streptozotocin in Wistar rats on biochemical indicators and oxidative stress in liver and kidney. Methods: Diabetes was induced neonatally by 100 mg of streptozotocin in Wistar rats. Blood glucose, insulin and oxidative stress indicators in liver and kidney were determined in 5 animals per group at days 5, 10, 20, 30, 60, 90 of birth. Results: Blood glucose and insulin showed significant differences in the STZ-group respect to the control group in all interventions. The maximum value of hyperglycemia was observed on day-5. The concentration of nitrates and nitrites in liver was higher than in kidney. In liver tissue of the STZ-group, this indicator was significantly higher on days 10-20 compared to the control. In all interventions, reduced glutathione consumption was demonstrated in the STZ-group compared to control in both organs. In the liver of STZ rats no lipid or protein damage was demonstrated. However, in the kidney, significant damage in both biomolecules was detected in the STZ-group on day-5. Conclusions: Neonatal streptozotocin cytotoxicity as well as induced glucose and insulin concentrations had a negative impact on oxidative stress indicators studied in liver and kidney tissue(AU)

Effect on hyperglycemia and pancreas cells of chaya aqueous extracts from two different regions in streptozotocin-induced diabetes rats

Cnidoscolus chayamansa is a native plant of the Mayan region, which is also cultivated in other places like northern Mexico, Tunisia and India. Many properties are attributed to Mayan Chaya, such as aid in the control of glycemia in diabetics. Thus this study aimed to evaluate the hypoglycemic effects of chaya aqueous extracts in a model of streptozotisin-induced diabetic Wistar rats. Chaya aqueous extracts were collected from plants cultivated in Quinta Roo (Mayan region) and Durango (northern Mexico), and in this study we compare their effect with metformin (as a control). Additionally, we compared the extracts mass profiles from both regions by high-resolution liquid chromatography coupled to a triple quadrupole tandem mass detector (HPLC-MS/MS QQQ). Finally, a study of the pancreatic tissue was carried out to evaluate the effects of the extracts on the Langerhans islets. Both extracts showed a good hypoglycemic effect after two weeks of treatment, and the Langerhans islets showed a partial recovery due to the effect of the treatment. Although the plants were cultivated at a distance of 2,350 km and under different weather, the compounds found in both did not show significant differences.

Consumo de jugo de granada (Punica granatum) y su efecto sobre la glucemia, perfil lipídico e histología del páncreas en un modelo de hiperglucemia inducida mediante estreptozotocina / Pomegranate juice consumption (Punica granatum) and its effect on glycemia, lipid profile and histology of the pancreas in a model of induced hyperglycemia by streptozotocin

Diversos compuestos bioactivos de los alimentos se han empleado en el tratamiento alterativo de la diabetes mellitus. El jugo de granada posee un alto contenido en compuestos fenólicos a los cuales se les atribuyen propiedades biológicas como hipolipemiante, hipoglucemiante y protector del tejido pancreático. El objetivo de este estudio fue evaluar el efecto del libre acceso de jugo de granada sobre los niveles de glucosa, colesterol, triglicéridos e integridad del tejido pancreático in vivo. Se emplearon 18 ratas macho Wistar inducidas a hiperglucemia con 60 mg estreptozotocina/kg de peso corporal intraperitoneal (IP). Se formaron tres grupos experimentales. El grupo HS expuesto a solución de sacarosa, el grupo HJG expuesto a jugo de granada y el grupo HSI expuesto a solución de sacarosa y tratamiento con insulina. Los resultados mostraron que, las ratas del grupo HJG consumieron jugo de granada durante 21 días, lo que resultó en la reducción de los niveles de glucosa con respecto a su valor inicial de 417 a 356 mg/dL, no de manera significativa (p>0.05). Los niveles de lípidos mostraron una reducción no significativa al finalizar la intervención (p>0.05). El estudio histológico del páncreas en el grupo HJG mostró conservación de la arquitectura pancreática y presencia de islotes de Langerhans; mientras que el grupo HS mostró extensa necrosis pancreática y el grupo HSI mostró daño intermedio con escasos islotes de Langerhans. Se sugiere que el jugo de granada posee efectos hipoglucemiantes y protege el tejido pancreático en ratas hiperglucémicas inducidas(AU)

Diverse bioactive compounds of foods have been used in the alternative treatment of diabetes mellitus. Pomegranate juice has a high content of phenolic compounds to which biological properties are attributed as lipid-lowering, hypoglycemic and protective of pancreatic tissue. The objective of this study was to evaluate the effect of free access of pomegranate juice on the levels of glucose, cholesterol, triglycerides and the integrity of pancreatic tissue in vivo. Eighteen male Wistar rats were induced to hyperglycemia with 60 mg streptozotocin/kg of body weight intraperitoneal (IP). Three experimental groups were formed. The HS group exposed to sucrose solution, the HJG group exposed to pomegranate juice and the HSI group exposed to sucrose solution and insulin treatment. The results showed that the rats of the HJG group consumed pomegranate juice for 21 days, which resulted in the reduction of glucose levels from its initial value of 417 to 356 mg/dL, not significantly (p>0.05). Lipid levels showed a non-significant reduction at the end of the intervention (p>0.05). The histological study of the pancreas in the HJG group showed conservation of the pancreatic architecture and the presence of islets of Langerhans; while the HS group showed extensive pancreatic necrosis and the HSI group showed intermediate damage with few islets of Langerhans. It is suggested that pomegranate juice has hypoglycaemic effects and protects pancreatic tissue in induced hyperglycemic rats(AU)

Time-dependent changes of calbindin D-28K and parvalbumin immunoreactivity in the hippocampus of rats with streptozotocin-induced type 1 diabetes

The hippocampus is affected by various stimuli that include hyperglycemia, depression, and ischemia. Calcium-binding proteins (CaBPs) have protective roles in the response to such stimuli. However, little is known about the expression of CaBPs under diabetic conditions. This study was conducted to examine alterations in the physiological parameters with type 1 diabetes induced with streptozotocin (STZ) as well as time-dependent changes in the expression of two CaBPs changes of were being evaluated. Rats treated with STZ (70 mg/kg) had high blood glucose levels (>21.4 mmol/L) along with increased food intake and water consumption volumes compared to the sham controls. In contrast, body weight of the animals treated with STZ was significantly reduced compared to the sham group. CB-specific immunoreactivity was generally increased in the hippocampal CA1 region and granule cell layer of the dentate gyrus (DG) 2 weeks after STZ treatment, but decreased thereafter in these regions. In contrast, the number of PV-immunoreactive neurons and fibers was unchanged in the hippocampus and DG 2 weeks after STZ treatment. However, this number subsequently decreased over time. These results suggest that CB and PV expression is lowest 3 weeks after STZ administration, and these deficits lead to disturbances in calcium homeostasis.

Caracterización de un modelo de diabetes tipo 2 en ratas y evaluación del papel de la angiotensina II y las especies reactivas de oxígeno en la resistencia neuronal a la insulina / Characterization of a type 2 diabetes model in rats and evaluation of the role of angiotensin II and reactive oxygen species in neuronal insulin resistance

La regulación ejercida por la insulina central en individuos diabéticos ha sido muy poco estudiada. La angiotensina II promueve el estrés oxidativo y la resistencia a la insulina. Dada la co-localización del receptor AT1 de la angiotensina II y el RI a nivel hipotalámico, en este trabajo, decidimos evaluar el efecto de la angiotensina II sobre las acciones centrales de la insulina en condiciones diabéticas, a través de un modelo animal de DM2 en ratas Sprague-Dawley, así como el posible efecto protector del tratamiento crónico con Valsartán. El modelo fue caracterizado y validado a través de la medición de diversos parámetros metabólicos, usando técnicas enzimáticas e inmunoenzimáticas. Los efectos de la angiotensina II sobre la señalización y acciones biológicas de la insulina a nivel hipotalámico fueron evaluadas in vivo e in vitro, mediante western blot, así como los cambios en los niveles de glicemia en las ratas tratadas ICV con ANG II y/o insulina. Fue evaluado además, el estado oxidativo a nivel hipotalámico, mediante la determinación de enzimas antioxidantes, así como el estado inflamatorio sistémico, mediante la determinación fluorométrica de citoquinas plasmáticas. El modelo experimental desarrollado mimetizó las características fenotípicas de la DM2. El valsartán previno parcialmente la resistencia a la insulina. En condiciones normales, se demostró que la angiotensina es capaz de inhibir la señalización de la insulina a nivel hipotalámico por un mecanismo dependiente de ERO. En condiciones diabéticas, hay una disminución basal de la activación de las proteínas de señalización de la insulina, la cual fue prevenida por el tratamiento con valsartán. El efecto hipoglicemiante inducido por la insulina central fue significativamente reducido en condiciones diabéticas. El tratamiento ICV con angiotensina II antagonizó los efectos hipoglicemiantes de la insulina central y este efecto fue potenciado en condiciones diabéticas. El valsartán bloquea la acción inducida por la ANG II ICV en todos los grupos. Los resultados demuestran que existe un estado de resistencia a la insulina en nuestro modelo de DM2, evidente tanto a nivel molecular como fisiológico, el cual es potenciado por la angiotensina y prevenido parcialmente por el tratamiento crónico con valsartán.

Repression of Ppargcla gene in liver of hyperglycemic rats induced with high fat diet combined with streptozotocin / Represión del gen Ppargc1a en hígado de ratas con hiperglicemia inducida por dieta alta en grasas combinada con estreptozotocina

Type 2 diabetes mellitus implies deregulation of multiple metabolic processes, being the maintenance of glycemia one of the most important. Many genes are involved in the deregulation of this particular process. Therefore, the aim of this study was to evaluate gene expression of genes related to type 2 diabetes mellitus, in the liver and pancreas of rats with hyperglycemia induced by high fat diet along with a low single dose of streptozotocin. Ahsg and Ppargc1a genes were studied in liver, whereas Kcnj11 and Slc2a2 genes were analyzed in pancreas. For this purpose, 210-240 g female rats were fed a high fat diet or a control diet for three weeks. At day 14, animals fed with high fat diet were injected with a single low dose of streptozotocin (35 mg/kg) and the control group rats were injected only with the vehicle. Plasmatic glucose, triglycerides and total cholesterol levels were measured at the beginning, day 14 and end of treatment. Body weight was also measured. Once the treatment was complete, rats were appropriately euthanized and then, pancreas and liver were surgically removed and frozen in liquid nitrogen. Total RNA was isolated using TRIzol reagent, treated with DNase I and reversely transcribed to cDNA. Gene expression analysis was performed using SYBR Green ­ Real time PCR and comparative Cq method, using three reference genes. Rats fed with high fat diet and treated with streptozotocin showed higher values of plasmatic glucose (17.09 +/- 0.43 vs. 5.91 +/- 0.29 mmol/L, p < 0.01) and a minor expression of Ppargc1a versus the control group (2-fold less expressed, p < 0.05) in liver. We conclude that repression of Ppargc1a gene may be an important process in the establishment of chronic hyperglycemia, probably through deregulation of hepatic gluconeogenesis. However, further studies need to be performed in order to clarify the role of Ppargc1a deregulation in liver glucose homeostasis.

La diabetes mellitus tipo 2 implica desregulación de varios procesos metabólicos, siendo la mantención de la glicemia uno de los más importantes. Varios genes están involucrados en este proceso. Así, el objetivo del presente estudio fue evaluar la expresión génica de genes relacionados a diabetes mellitus tipo 2 en hígado y páncreas de ratas con hiperglicemia inducida con una dieta alta en grasas junto con una baja dosis de estreptozotocina. Ratas hembra de 210 - 240 g fueron alimentadas con una dieta alta en grasas o con una dieta control por tres semanas. Al día 14, los animales alimentados con dieta alta en grasas fueron inyectados con una dosis baja de estreptozotocina (35 mg/kg), mientras las del grupo control fueron inyectadas con el vehículo. El peso corporal y las concentraciones plasmáticas de glucosa, triglicéridos y colesterol total, fueron medidos al inicio, al día 14 y al final del tratamiento. Al finalizar el tratamiento, los animales fueron sacrificados, el hígado y páncreas fueron quirúrgicamente removidos e inmediatamente congelados en nitrógeno liquido. El RNA fue extraído usando el reactivo TRIzol, tratado con DNasa I y posteriormente convertido a cDNA. Los análisis de expresión génica fueron realizados usando SYBR Green - real time PCR y el método del Cq comparativo. En hígado se estudiaron los genes Ahsg y Ppargc1a, mientras que en páncreas se analizaron los genes Slc2a2 y Kcnj11. Las ratas alimentadas con dieta alta en grasas y tratadas con streptozotocina mostraron niveles mayores de glucosa plasmática (17,09 +/- 0,43 vs. 5,91 +/- 0,29 mmol/L, p < 0,01) y una menor expresión hepática de Ppargc1a versus el grupo control (2 veces menor expresión, p < 0,05). En conclusión, la represión del gen Ppargc1a puede ser un importante proceso en el establecimiento de la hiperglicemia crónica, probablemente debido a una desregulación de la gluconeogénesis hepática. Sin embargo, estudios adicionales son necesarios para esclarecer el rol de esta...

Streptozotocin-induced mechanical hypernociception is not dependent on hyperglycemia

Since streptozotocin (STZ)-induced diabetes is a widely used model of painful diabetic neuropathy, the aim of the present study was to design a rational protocol to investigate whether the development of mechanical hypernociception induced by STZ depends exclusively on hyperglycemia. Male Wistar rats (180-200 g; N = 6-7 per group) received a single intravenous injection of STZ at three different doses (10, 20, or 40 mg/kg). Only the higher dose (40 mg/kg) induced a significant increase in blood glucose levels, glucose tolerance and deficiency in weight gain. However, all STZ-treated rats (hyperglycemic or not) developed persistent (for at least 20 days) and indistinguishable bilateral mechanical hypernociception that was not prevented by daily insulin treatment (2 IU twice a day, sc). Systemic morphine (2 mg/kg) but not local (intraplantar) morphine treatment (8 µg/paw) significantly inhibited the mechanical hypernociception induced by STZ (10 or 40 mg/kg). In addition, intraplantar injection of STZ at doses that did not cause hyperglycemia (30, 100 or 300 µg/paw) induced ipsilateral mechanical hypernociception for at least 8 h that was inhibited by local and systemic morphine treatment (8 µg/paw or 2 mg/kg, respectively), but not by dexamethasone (1 mg/kg, sc). The results of this study demonstrate that systemic administration of STZ induces mechanical hypernociception that does not depend on hyperglycemia and intraplantar STZ induces mechanical sensitization of primary sensory neurons responsive to local morphine treatment.

A microcirculação da bolsa da bochecha do hamster sob a influência do diabetes mellitus experimental induzido por estreptozotocina: aspectos morfofuncionais / Microcirculation of hamster cheek pouch under the influence of experimental Diabetes Mellitus induced by streptozotocin: morpho-functional aspects

O Diabetes Mellitus é uma doença metabólica crônica com múltiplos fatores etiológicos (genético, viral e imunológico) que condiciona deficiência absoluta ou relativa de insulina, causando persistência de níveis elevados de glicose no sangue. Atualmente, o Diabetes Mellitus é considerado um importante problema de saúde devido a sua prevalência e alta morbimortalidade. Sua importância clínica resulta essencialmente de suas graves complicações, especialmente as microvasculares. A hiperglicemia crônica ou intermitente tem sido identificada como o fator indutor de lesão endotelial, sendo este, o agente desencadeante das complicações microvasculares. As células endoteliais, por serem influenciadas pela força hemodinâmica local, respondem com a transdução de sinais (mecanotrans dução), as quais podem ser responsáveis pelo início de processos patológicos na parede dos vasos. Desta forma, o objetivo deste estudo foi analisar a microcirculação da bolsa da bochecha do hamster sob a influência do Diabetes Mellitus tipo 1 experimental induzido por estreptozotocina, avaliando seus aspectos morfofuncionais aos 6 e 15 dias de evolução da doença. As características morfológicas de arteríolas e vênulas foram estimadas por medidas do diâmetro do lúmen e da espessura da parede; pela densidade de volume e de área destes vasos na bolsa da bochecha; pela análise imunohistoquímica da expressão de actina, talina, alfa-actina de músculo liso, vimentina, laminina e colágeno IV através da microscopia de luz com a utilização de um sistema semiquantitativo baseado em uma escala de intensidade de imunomarcação; e por microscopia eletrônica de transmissão. Também foi avaliado o relaxamento dependente do endotélio, medido pela variação do diâmetro do lúmen antes e após a aplicação de acetilcolina e a permeabilidade de vênulas pós-capilares à histamina, determinada pelo número de pontos de extravasamento plasmático. Nossos resultados mostraram que arteríolas e vênulas...

Diabetes Mellitus is a chronic metabolic disease with multiple etiologic factors (genetic, viral and immunological) that results in absolute or relative insulin deficiency, causing persistent elevated blood glucose levels. Nowadays, Diabetes Mellitus is considered as an important health concern due to its increasing prevalence and high morbimortality. Its clinical importance comes from the complications, especially harm inductor factor, being this the first outcome of microvascular complications. Endothelial cells, under local hemodynamic strength, produce signal transduction (mechanotransduction), which can be responsible for the beginning of patholgical events in vessels wall. In this regard, the objective of this study was to analyze hamster cheek pouch microcirculation under the influence of type 1 diabetes mellitus induced by streptozotocin, evaluationg its morpho-functional aspects at 6 and 15 days of diseases evolution. Morphological characteristics of arterioles and venules were estimated by the measurement of lumen diameter and wall thickness; the volume density and area of these vessels from cheek pouch; immunohistochemistry of the expression of actin, talin, smooth muscle alpha-actin, vimentin, laminin and type IV collagen through light microscopy with the utilization of a semi-quantitative score system based on the intensity of the immunostaining; and transmission electron microscopy. It was also evaluated the endothelium dependent relaxation, measured by the variation of lumen diameter before and after acetylcholine administration and post-capillary venules permeability to histamine, determined by number of points of plasma extravasation. Our results reveal that arterioles and venules do not show differences between the groups concerning wall thickness, luminal diameter, density per area and volume density. Vascular permeability, after 2 minutes of histamine administration, was reduced significantly in diabetic groups...

effect of oral administration of chard on contractile reactivity of isolated aorta in diabetic rats

Chard [Beta vulgaris L. var. Cicla] administration could improve the activity of antioxidant systems such as gluthatione and has a hypoglycemic and hypolipidemic property. To evaluate the effect of oral administration of chard on the contractile reactivity of isolated aorta in diabetic rats. This experimental study was conducted at the School of Medicine, Shahed University in 2003. Male Wistar rats were divided into control, chard-treated control, diabetic, and chard-treated diabetic groups. For induction of diabetes, streptozotcin [STZ] was intraperitoneally administered [60 mg/Kg]. Chard-treated groups received chard mixed with standard pelleted food at a weight ratio of 1/15. After one month, contractile reactivity of aortic rings to KC1 and noradrenaline was determined using isolated tissue setup. Serum glucose level showed a significant increase [409/4 and 401/3 mg/dl] in diabetic group at 2[nd] and 4[th] weeks [P<0.001], while this increase was less obvious in chard-treated diabetic group [274/5 and 161/2 mg/dl] [P<0.01 and P<0.001 for 2[nd] and 4[th] weeks, respectively]. In addition, the latter group showed a lower contraction to KC1 [P<0.05] and noradrenaline [P<0.01] as compared to diabetic group [0/76 and 1.41 g/mm [2] of the aortic ring]. Meanwhile, there was no significant difference between control and chard-treated control groups regarding contractile reactivity. Oral administration of chard for one month could attenuate the contractile responsiveness of the vascular system and may prevent the development of hypertension in diabetic rats

Effect of alpha lipoic acid, melatonin and trans resveratrol on intracerebroventricular streptozotocin induced spatial memory deficit in rats.

In the present study, the effect of antioxidants-alpha lipoic acid, melatonin and trans resveratrol were studied against intracerebroventricular streptozotocin induced spatial memory deficit. Male Wistar rats were injected with intracerebroventricular streptozotocin bilaterally. The rats were treated chronically with alpha lipoic acid (200 mg/kg, po), melatonin (20 mg/kg, ip) and trans resveratrol (20 mg/kg, ip) for 18 days starting from day 1 of streptozotocin injection in separate groups. The spatial memory was evaluated using the Morris water maze task. The intracerebroventricular streptozotocin rats treated with antioxidants showed significantly less spatial memory deficit both in the acquisition and probe trials as compared to the vehicle treated rats. The study demonstrated the effectiveness of alpha lipoic acid, melatonin and trans resveratrol in preventing spatial memory deficit induced by intracerebroventricular streptozotocin and it's potential in age related neurodegenerative disorders where oxidative stress is involved such as Alzheimer's disease.

Early stereological changes in liver of Sprague-Dawley rats after streptozotocin injection.

BACKGROUND: Diabetes mellitus is associated with biochemical, physiological and pathologic alterations in the liver. We measured changes in structure of rat liver after streptozotocin injection, using stereology. METHODS: Livers of 36 streptozotocin-injected rats were removed after 4, 8 and 12 weeks. Liver volume and weight were measured, and volume-weighted mean volume of hepatocytes and their nuclei were estimated in periportal (Z1), interstitial (Z2) and perivenous (Z3) zones of liver acini. Volume of liver sinusoids was also estimated. RESULTS: Mean volume and weight of the liver were reduced by 15% and 12%, respectively at 4 and 8 weeks after injection. Mean hepatocyte volumes were reduced by approximately 30%, 31% and 24% in Z1, Z2 and Z3 at 4 weeks, 19% and 24% in Z2 and Z3 at 8 weeks, and 14% in Z1 at 12 weeks. Mean volume of hepatocyte nuclei was reduced by approximately 18% and 20% in Z2 and Z3 at 4 weeks, 23% in all three zones at 8 weeks, and 18%, 15% and 13% in Z1, Z2 and Z3, respectively, at 12 weeks. The absolute volume of the sinusoids decreased by 16.5% only at 4 weeks. CONCLUSION: Streptozotocin injection leads to early reduction in volume of hepatocytes, their nuclei and sinusoids in rat liver.

Hypoglycemic effect of Hibiscus rosa sinensis L. leaf extract in glucose and streptozotocin induced hyperglycemic rats.

Investigations were carried out to evaluate the effect of aqueous extract of H. rosa sinensis leaves on blood glucose level and glucose tolerance using Wistar rats. Repeated administration of the extract (once a day for seven consecutive days), at an oral dose equivalent to 250 mg kg(-1), significantly improved glucose tolerance in rats. The peak blood glucose level was obtained at 30 min of glucose load (2 g kg(-1)), thereafter a decreasing trend was recorded up to 120 min. The data exhibit that repeated ingestion of the reference drug tolbutamide, a sulphonylurea and the extract brings about 2-3 fold decrease in blood glucose concentration as compared to single oral treatment. The results clearly indicate that tolbutamide improves the glucose tolerance by 91% and extract does so only by 47%. At 250 mg kg(-1), the efficacy of the extract was 51.5% of tolbutamide (100mg kg(-1)). In streptozotocin diabetic rats, no significant effect was observed with the extract, while glibenclamide significantly lowered the glucose level up to 7 hr. These data suggest that hypoglycemic activity of H. rosa sinensis leaf extract is comparable to tolbutamide and not to glibenclamide treatment.

Análise histomorfométrica da reparaçäo de alvéolos infectados após extraçäo dental em ratos diabéticos controlados e näo controlados / Histomorphometric analusis of infected denta socket repair after tooth extraction in controlled and uncontrolled diabetics rats

O processo de reparo em alvéolos dentais infectados de ratos (Rattus novegicus, albinus, Wistar) diabéticos controlado e näo controlado foi avaliado qualitativa e quantitativamente. Para isso foram utilizados 60 animais. O Grupo I (Controle) foi submetido à inoculaçäo de soluçäo tampäo, os Grupos II e III (Diabéticos) receberam estreptozotocina (45mg/Kg), dissolvida em tampäo citrato 0,01M, sendo administradas 3 unidades/dia de insulina apenas no Grupo III (Diabético controlado). Após a verificaçäo do estado glicêmico dos animais, todos os incisivos superiores direitos foram extraídos e induziu-se a alveolite com soluçäo salina pré-reduzida e epinefrina. Os animais foram sacrificados no 3§, 7§, 14§ e 28§ dias pós-operatórios. Suas maxilas foram separadas, fixadas em formalina, descalcificadas em EDTA e incluídas em parafina. Os cortes com 6µm de espessura foram corados com Hematoxilina e eosina (H.E.) e Tricrômio de Masson. Após a análise qualitativa e quantitativa ao microscópio óptico e histometria óssea com o Software Imagelab, os resultados foram submetidos ao teste de Kruskal-Wallis. Concluiu-se que: qualitativamente o reparo alveolar do grupo diabético näo controlado foi mais retardado em relaçäo ao controle e ao diabético controlado nas últimas fases da reparaçäo sem apresentar diferenças estatisticamente significantes

Biochemical studies on the effect of S-1,3-butanediol of diabetes induced rats.

The biochemical effect of S-1,3-butanediol on streptozotocin induced diabetic rats was studied. Rats were made diabetic by the intraperitoneal injection of 40 mg/kg body weight streptozotocin in sodium citrate buffer. A dosage of 25 mmol/kg body weight of S-1,3-butanediol was injected intraperitoneally for treatment. The streptozotocin induced diabetic rats showed a marked increase in blood glucose level, and significant increase in the level of cholesterol, triglycerides and free fatty acids. The glycogen levels in liver and kidney were greatly decreased in diabetic rats. Treatment with butanediol normalised the glucose and glycogen level but had no significant effect on protein and lipid levels.