La suplementación con zinc favorece el crecimiento intrauterino en fetos de ratas diabéticas / Zinc supplementation favours intrauterine growth in diabetic rat fetuses

La deficiencia de zinc puede ser un factor mediador en los trastornos del crecimiento fetal en la descendencia de la gestante diabética. Se persiguió como objetivo determinar la influencia de un suplemento con zinc sobre la morfometría externa corporal y craneofacial en fetos de ratas diabéticas con hiperglucemias moderadas. Durante la gestación, ratas diabéticas y controles fueron suplementadas por vía oral con sulfato de zinc (50 mg/kg-pc) o no recibieron tratamiento. Los fetos descendientes del grupo diabético suplementado presentaron niveles similares a los controles en las variables de crecimiento somático determinadas. La suplementación con zinc a ratas diabéticas favoreció el crecimiento intrauterino en los fetos. Los resultados de esta investigación constituyen aportes para dilucidar los requerimientos de zinc que permitan prevenir los trastornos del crecimiento fetal en la descendencia de gestantes diabéticas.

Zinc deficiency may be a mediating factor in fetal growth disorders in the offspring of diabetic pregnant women. The objective was to determine the influence of a zinc supplement on external body and craniofacial morphometry in diabetic rat fetuses with moderate hyperglycemia. During gestation, diabetic and control rats were orally supplemented with zinc sulphate (50 mg/kg bw) or received no treatment. The fetuses descendants of the supplemented diabetic group had levels similar to the control ones in the determined somatic growth variables. Zinc supplementation to diabetic rats favoured intrauterine growth in fetuses. The results of this research constitute a contribution to elucidate zinc requirements that allow preventing fetal growth disorders in the offspring of diabetic pregnant women.

Uncontrolled Diabetes with Underlying Structural Changes in the Atrioventricular Node / Diabetes no Controlada con Cambios Estructurales Subyacentes en el Nodo Atrioventricular

SUMMARY: Diabetic cardiomyopathy, characterized by diabetes mellitus (DM) -induced cardiac muscular abnormalities, is a strong inducer of impaired cardiac contraction and arrhythmia. Atrioventricular block, a serious type of arrhythmia resulting from interruption of cardiac impulse conduction via the atrioventricular node (AVN), frequently occurs among diabetic patients. However, details of structural changes in AVN in DM remain poorly explained. Here, this study defined the effects of DM on the morphological remodeling of the AVN in male Sprague Dawley rats induced by intraperitoneal injection of streptozotocin (60 mg/kg body weight). At 24 weeks, the pathological changes in the AVN were assessed by light microscopy (LM) and transmission electron microscopy (TEM). Under LM, the AVN in diabetic rats became a less compact mass and exhibited the intracellular vacuolation. The nodal cells were more varied in sizes with the absence or shrinkage of nuclei and clear cytoplasm compared to the control. The collagen content significantly increased in relation to the presence of myofibroblasts. Consistent with LM, TEM images of the diabetic nodal cells revealed several signs of cell damage, such as mitochondrial changes, deterioration of cell organelles, gap junction internalization, and cell separation. Furthermore, changes in AVN innervation, evidenced by damaged Schwann cells and axons, were also found. These results indicated alterations in important components in the AVN during diabetic condition, which may lead to the impairment of electrical conduction, causing abnormal cardiac functions in diabetic patients.

La miocardiopatía diabética, caracterizada por anomalías musculares cardíacas inducidas por diabetes mellitus (DM), es un fuerte inductor de alteración de la contracción cardíaca y arritmia. El bloqueo atrioventricular, un tipo grave de arritmia resultante de la interrupción de la conducción del impulso cardíaco a través del nodo atrioventricular (NAV), se produce con frecuencia entre los pacientes diabéticos. Sin embargo, los detalles de los cambios estructurales en NAV en DM siguen estando pobremente explicados. Aquí, este estudio definió los efectos de la DM en la remodelación morfológica del NAV en ratas macho Sprague Dawley inducidas por inyección intraperitoneal de estreptozotocina (60 mg/kg de peso corporal). A las 24 semanas, los cambios patológicos en el NAV se evaluaron mediante microscopía óptica (MO) y microscopía electrónica de transmisión (MET). Bajo MO, el NAV en ratas diabéticas se convirtió en una masa menos compacta y exhibió la vacuolización intracelular. Las células nodales tenían tamaños más variados con ausencia o contracción de núcleos y citoplasma claro en comparación con el control. El contenido de colágeno aumentó significativamente en relación con la presencia de miofibroblastos. De acuerdo con MO, las imágenes MET de las células nodales diabéticas revelaron varios signos de daño celular, como cambios mitocondriales, deterioro de los orgánulos celulares, internalización de uniones comunicantes y separación celular. Además, también se encontraron cambios en la inervación del NAV, evidenciados por schwannocitos y axones dañados. Estos resultados indicaron alteraciones en componentes importantes en el NAV durante la condición diabética, lo que puede conducir al deterioro de la conducción eléctrica, causando funciones cardíacas anormales en estos pacientes.

Altered Chief Cell Morphology in the Gastric Gland of Streptozotocin-Diabetic Rats

SUMMARY: Diabetes mellitus (DM) is a metabolic disorder with rising incidences worldwide. Gastric symptoms of DM have been reported, including nausea, vomiting, bloating, and epigastric pain. Moreover, acute to chronic gastritis and atrophic gastritis occur in DM can affect the chief cells of the gastric gland. Chief cells are vital because of their ability to digest and separate vitamin B12 from protein. Lack of vitamin B12 leads to impaired DNA synthesis and abnormal metabolism in red blood cells, and eventually leading to pernicious anemia. Furthermore, decreased vibratory and positional senses, numbness, ataxia with subacute combined degeneration, and dementia are present in pernicious anemic patients. Twenty-four male adult Sprague-Dawley rats were used in this study. The rats were divided into control (n = 12) and diabetic (n = 12) groups. The rats were further separated into two categories: short-term (4 weeks) and long-term (24 weeks) groups. DM model was induced by manually injecting intraperitoneally with streptozotocin in citrate buffer at a dose of 60 mg/kg body weight. The same amount of buffer was injected into the control group. After sacrifice, three regions of the stomach (the cardia, body, and pylorus) were dissected. Histopathology was performed by staining with toluidine blue. Image analysis was used to quantify the zymogen granule accumulation in chief cells. The data were compared between the control and DM rats in each period using Student's t-test. In addition, transmission electron microscopy (TEM) was also used to examine the ultrastructures. There was a significant decrease in the percentage of zymogen granules in DM rats. Under TEM, the destructions of mitochondria, rough endoplasmic reticulum, and Golgi apparatus in the DM rat were observed in the chief cells. In rats with uncontrolled diabetes, there is damage to the chief cells all over the area of the stomach, affecting digestion and malabsorption of vitamin B12. Therefore, this result helps clinicians recognize that diabetic patients with gastric symptoms may have hidden pernicious anemia.

La diabetes mellitus (DM) es un trastorno metabólico con incidencia creciente a nivel mundial. Se han informado síntomas gástricos de DM, que incluyen náuseas, vómitos, distensión abdominal y dolor epigástrico. Además, la gastritis aguda a crónica y la gastritis atrófica que ocurren en la DM pueden afectar las células principales de la glándula gástrica. Las células principales son vitales debido a su capacidad para digerir y separar la vitamina B12 de las proteínas. La falta de vitamina B12 conduce a una síntesis de ADN deteriorada y un metabolismo anormal en los glóbulos rojos, lo que eventualmente conduce a una anemia perniciosa. Además, los pacientes con anemia perniciosa presentan disminución de los sentidos vibratorio y posicional, entumecimiento, ataxia con degeneración combinada subaguda y demencia. En este estudio se usaron 24 ratas Sprague-Dawley macho adultas. Las ratas se dividieron en grupos control (n = 12) y diabéticas (n = 12). Las ratas se separaron además en dos categorías: grupos a corto plazo (4 semanas) y a largo plazo (24 semanas). El modelo de DM se indujo inyectando manualmente por vía intraperitoneal estreptozotocina en tampón de citrato a una dosis de 60 mg/kg de peso corporal. Se inyectó la misma cantidad de tampón en el grupo control. Después del sacrificio, se disecaron tres regiones del estómago (cardias, cuerpo y píloro). La histopatología se realizó mediante tinción con azul de toluidina. El análisis de imágenes se utilizó para cuantificar la acumulación de gránulos de zimógeno en las células principales. Los datos se compararon entre las ratas control y DM en cada período utilizando la prueba t de Student. Además, se utilizó microscopía electrónica de transmisión (TEM) para examinar la ultraestructura celular. Hubo una disminución significativa en el porcentaje de gránulos de zimógeno en ratas DM. Bajo TEM, se observaron en las células principales las destrucción de las mitocondrias, del retículo endoplásmico rugoso y del complejo golgiense en la rata DM. En ratas con diabetes no controlada, hay daño en las células principales de toda el área del estómago, lo que afecta la digestión y la malabsorción de vitamina B12. Por lo tanto, este resultado ayuda a los médicos a reconocer que los pacientes diabéticos con síntomas gástricos pueden tener una anemia perniciosa oculta.

Biomechanical Effects of Angiotensin 1-7 in Diabetes Rats Femur / Efectos Biomecánicos de la Angiotensina 1-7 en el Fémur de Ratas Diabéticas

SUMMARY: It is known that diabetes mellitus has late complications, including microvascular and macrovascular diseases. Diabetes can affect bones through biochemical markers of bone structure, density, and turnover. This study aimed to biomechanically investigate the bone-protective effects of angiotensin 1-7 (Ang 1-7), one of the active peptides in the renin-angiotensin system, in rats with diabetes. Thirty male Wistar albino rats, three months old and weighing 250-300 g, were divided into four groups: diabetes, Ang 1- 7, diabetes plus Ang 1-7, and control. One month later, diabetes developed in rats; the rats were sacrificed, and their right femur was removed. Three-point bending biomechanical tests were performed on the femurs. The diabetic group had significantly higher bone fragility than the other groups (Pr >.05). Bone fragility was lower, and bone flexibility was higher in the Ang 1-7 groups (Pr>F value 0.05). As a result of our study, the effect of Ang 1-7 on the bones of rats with diabetes was investigated biomechanically. Ang 1-7 has a protective impact on the bones of rats with diabetes.

Se sabe que la diabetes mellitus tiene complicaciones tardías, incluyendo enfermedades microvasculares y macrovasculares. La diabetes puede afectar los huesos a través de los marcadores bioquímicos de la estructura, la densidad y el recambio óseo. Este estudio tuvo como objetivo investigar biomecánicamente los efectos protectores en los huesos de la angiotensina 1-7 (Ang 1-7), uno de los péptidos activos en el sistema renina-angiotensina, en ratas con diabetes. Treinta ratas albinas Wistar macho, de tres meses de edad y con un peso de 250-300 g, se dividieron en cuatro grupos: diabetes, Ang 1-7, diabetes más Ang 1-7 y control. Un mes después, se desarrolló diabetes en ratas; se sacrificaron los animales y se extrajo su fémur derecho. Se realizaron pruebas biomecánicas de flexión de tres puntos en los fémures. El grupo diabéticos tenía una fragilidad ósea significativamente mayor que los otros grupos (Pr > 0,05). La fragilidad ósea fue menor y la flexibilidad ósea fue mayor en los grupos Ang 1-7 (valor Pr>F 0,05). Como resultado de nuestro estudio, se determinó biomecánicamente el efecto de Ang 1-7 en los huesos de ratas con diabetes. Se concluye que Ang 1-7 tiene un impacto protector en los huesos de ratas diabéticas.

Histopathological examination of the protective effect of intense exercise in apoptotic germ cell damage due to diabetes

Purpose: The aim of this study was to determine the protective and antioxidative effects of intensive exercise on streptozotocin (STZ)-induced testicular damage, apoptotic spermatognial cells death, and oxidative stress. Methods: 36 male Sprague Dawley rats were divided into three groups: control, diabetes, and diabetes+intensive exercise (IE) groups. Testicular tissues were examined histopathologically and antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) activity, as well as serum testosterone level, were measured. Results: Seminiferous tubules and germ cells were found to be better in the testis tissue of the intense exercise group than in the diabetes group. Diabetes suppressed antioxidant enzymes CAT, SOD, GPx and testosterone levels were significantly decreased, and increased MDA level in the diabetic group compared to diabetes+IE group (p < 0.001). Following four weeks of treatment, intensive exercise improved the antioxidant defense, significantly decreased MDA activity, and increased testosterone levels in testicular tissue in the diabetic group compared to diabetes+IE group (p < 0.01). Conclusion: STZ-induced diabetes causes damage to the testis tissue. In order to prevent these damages, exercise practice has become very popular nowadays. In present study, our intensive exercise protocol, histological, and biochemical analysis of the effect of diabetes on the testicular tissues is shown.

Physiochemical and nutritional evaluation of whole kumquat fruits powder and its protective effect on thyroid hormones and blood sugar levels in diabetic rats / Avaliação físico-química e nutricional de frutas inteiras de kumquat em pó e seu efeito protetor sobre os hormônios da tireoide e os níveis de açúcar no sangue em ratos diabéticos

Abstract The present study was conducted to evaluate the chemical composition, antioxidant activity and hypoglycemic effects of whole kumquat (Ku) powder in diabetic rats fed a high-fat-high-cholesterol (HFHC) diet. The antioxidant activities were evaluated using stable 1,1-diphenyl 2-picrylhydrazyl (DPPH) free radical scavenging method, 2,2´-azinobis (3-ethyl benzo thiazoline-6-sulphonic acid) radical cation (ABTS) and Ferric reducing antioxidant power (FRAP). Total phenolic content was (51.85 mg GAE/g) and total flavonoid content was (0.24 mg Cateachin Equivalent, CE/g). DPPH and ABTS values were 3.32 and 3.98 mg Trolox equivalent (TE)/g where FRAP value was 3.00 mM Fe2+/kg dry material. A total of 90 albino rats were used in the present study. Rats group were as follows: normal diet; normal treated (2, 4, and 6% Ku.), diabetic rats (non-treated), diabetic + HFHC diet (non-treated), HFHC (non-treated), Diabetic (treated), HFHC (treated) and Diabetic + HFHC (treated). The diets were followed for 8 weeks. Blood samples were collected at the end of the experiment. Serum glucose was recorded and thyroid hormones (T4, Thyroxine and T3, Triiodothyronine) were conducted. Diet supplemented with Kumquat at different concentrations have a hypoglycemic effect and improve the thyroid hormones of both diabetic rats and HFHC diabetic rats.

Resumo O presente estudo foi conduzido para avaliar a composição química, a atividade antioxidante e os efeitos hipoglicêmicos do pó de kumquat (Ku) em ratos diabéticos alimentados com uma dieta rica em gordura e colesterol (HFHC). As atividades antioxidantes foram avaliadas usando o método de eliminação de radicais livres de 1,1-difenil 2-picrilhidrazil (DPPH), 2,2'-azinobis (ácido 3-etilbenzotiazolina-6-sulfônico) radical cátion (ABTS) e antioxidante redutor férrico potência (FRAP). O conteúdo fenólico total foi (51,85 mg GAE / g) e o conteúdo total de flavonoides foi (0,24 mg Cateachin Equivalent, CE / g). Os valores de DPPH e ABTS foram 3,32 e 3,98 mg equivalente de Trolox (TE) / g, em que o valor de FRAP foi de 3,00 mM Fe2 + / kg de material seco. Um total de 90 ratos albinos foi usado ​​no presente estudo. O grupo dos ratos foi o seguinte: dieta normal: tratados normais (2, 4 e 6% Ku.), ratos diabéticos (não tratados), diabéticos + dieta HFHC (não tratados), HFHC (não tratados), diabéticos (tratados), HFHC (tratados) e diabéticos + HFHC (tratados). As dietas foram seguidas por 8 semanas. Amostras de sangue foram coletadas ao final do experimento. A glicose sérica foi registrada e os hormônios tireoidianos (T4, Tiroxina e T3, Triiodotironina) foram conduzidos. A dieta suplementada com kumquat em diferentes concentrações tem um efeito hipoglicêmico e melhora os hormônios tireoidianos tanto de ratos diabéticos quanto de ratos diabéticos com HFHC.

Experimental model of nephropathy associated with diabetes mellitus in mice

Purpose: Nontransmissible chronic diseases, such as diabetes mellitus (DM) and nephropathy, affect a significant portion of the population, often treated due to injuries that require healing and regeneration. To create an experimental model of associated comorbidities, for healing and regeneration studies, protocols for induction of nephropathy by ischemia and reperfusion (I/R) and induction of DM by injection of streptozotocin (STZ) were associated. Methods: Sixty-four mice (Mus musculus), female, adult, Swiss strain, weighing approximately 20 g, were divided into four groups: G1: control (n = 24), G2: nephropathy group (N) (n = 7), G3, DM (n = 9), and G4: N+DM (n = 24). Arteriovenous stenosis (I/R) of the left kidney was performed as the first protocol. The animals received a hyperlipidemic diet for 7 days after the injection of STZ (150 mg/kg, via i.p.) and an aqueous glucose solution (10%) for 24 h. The animals in the G3 and G4 groups were observed for 14 days before receiving the diet and STZ. The evolution of nephropathy was observed using a urine test strip and the DM, through the analysis of blood glucose with a reagent strip on a digital monitor. Results: The ischemic induction protocols of nephropathy and DM with STZ, associated, were sustainable, low-cost, and without deaths. There were alterations compatible with initial renal alterations, in the first 14 days, such as increased urinary density, pH alteration, presence of glucose, proteins and leukocytes, when compared to the control group. DM was confirmed by the presence of hyperglycemia 7 days after induction and its evolution after 14 days. The animals in the G4 group showed constant weight loss when compared to the other groups. It was possible to observe morphological alterations in the kidneys submitted to I/R, regarding coloration, during surgery and after the end of the observation period, in the volume and size of the left kidney, when compared to the contralateral kidney. Conclusion: It was possible to induce nephropathy and DM associated in the same animal, in a simple way, confirmed with rapid tests, without losses, providing a basis for future studies.

Antioxidant, Antidiabetic and Lipid Profiling of Spermadicyton Suaveolens in Streptozotocin (STZ) Induced Diabetic Rats

ABSTRACT Diabetes is a life-threatening disease, and currently available synthetic medicines for treating diabetes are associated with various side effects. Therefore, there is an unmet need to develop herbal remedies against diabetes as an alternative to synthetic medicines. Although local healers use the roots of Spermadicyton suaveolens (SS) to manage diabetes, there is negligible research to validate its antidiabetic properties. The present investigation aims to the assess the antioxidant, antidiabetic, and antihyperlipidemic potential of the ethanolic extract of S. Suaveolen's roots (EESS) on streptozotocin (STZ) induced diabetic rats. The extract was screened for in vitro antioxidant and antidiabetic activity. The in vivo antidiabetic potential of EESS (at 200 and 400 mg/kg) was studied on STZ-induced diabetic rats for 20 days. The EESS displayed significant (p<0.05) antidiabetic and antioxidant properties. The administration of 200 mg/kg and 400 mg/kg EESS in STZ-induced diabetic rats significantly reduced hyperglycemia, and restored antioxidant enzymes and lipid profile-a high density lipoprotein (HDL) increased by the administration of a single dose of streptozotocin. Thus, EESS could be a promising herbal medicine in the treatment of diabetes and hyperlipidemia

Efecto de la suplementación del zinc sobre el peso fetal en ratas diabéticas gestadas / Effect of zinc supplementation on fetal weight in pregnant diabetic rats

RESUMEN Introducción: La relación entre la deficiencia de Zn y la elevada incidencia de alteraciones en el crecimiento intrauterino en la diabetes materna aún no se ha dilucidado. En la literatura consultada no existen reportes del efecto de la suplementación con el micronutriente sobre el crecimiento fetal en modelos de diabetes con hiperglucemias moderadas. Objetivo: Determinar el efecto sobre el peso fetal de la suplementación con zinc a ratas con diabetes moderada durante la gestación. Métodos: Se utilizó un modelo de diabetes moderada inducida en ratas Wistar al segundo día de nacidas por inducción subcutánea con estreptozotocina (100mg/kg-pc). En la adultez las ratas sanas y diabéticas fueron apareadas con machos sanos. Según correspondiera recibieron durante 20 días de gestación un suplemento de sulfato de zinc (50mg/kg). Se estudiaron 395 fetos de cuatro grupos: fetos de ratas sanas sin suplemento, de ratas sanas suplementadas, de ratas diabéticas sin suplemento y de ratas diabéticas suplementadas. Los fetos se clasificaron en pequeños (PEG), adecuados (AEG) y grandes (GEG) para la edad gestacional. Resultados: La descendencia de las ratas diabéticas suplementadas mostró valores del peso fetal similares a ambos grupos sanos al término de la gestación, presentando menor porcentaje de fetos PEG y GEG, así como mayor porcentaje de AEG respecto al grupo diabético no suplementado. Conclusiones: La suplementación con Zn durante la gestación a ratas diabéticas con hiperglucemias moderadas causó efectos positivos sobre su descendencia al aumentar el porcentaje de fetos con peso adecuado.

ABSTRACT Introduction: the relationship between Zn deficiency and the high incidence of abnormal intrauterine growth in maternal diabetes has not yet been elucidated. There are no reports in the consulted literature of the effect of micronutrient supplementation on fetal growth in models of diabetes with moderate hyperglycemia. Objective: to determine the effect of zinc supplementation on fetal weight in rats with moderate diabetes during pregnancy. Methods: a model of mild diabetes was used in Wistar rats on the second day of birth by subcutaneous streptozotocin induction (100mg/kg-bw). As adults, healthy and diabetic rats were mated with healthy males. As appropriate, they received a zinc sulfate supplement (50mg/kg) during 20 days of gestation. A number of 395 fetuses from four groups were studied: fetuses from healthy rats without supplementation, from healthy rats supplemented, from diabetic rats without supplementation and from diabetic rats supplemented. Fetuses were classified as small (SGA), adequate (AGA), and large (LGA) for gestational age. Results: the offspring of the supplemented diabetic rats showed similar fetal weight values to both healthy groups at the end of pregnancy, having a lower percentage of SGA and LGA fetuses, as well as a higher percentage of AGA compared to the non-supplemented diabetic group. Conclusions: Zn supplementation during pregnancy in diabetic rats with moderate hyperglycemia had positive effects on their offspring by increasing the percentage of fetuses with adequate weight.

Endothelial expression of the receptor for advanced glycation end products in experimental diabetes / Expresión endotelial del receptor para productos finales de glicación avanzada en diabetes experimental

The receptor for advanced glycation end products (RAGE) is implicated in the pathogenesis of several chronic diseases including diabetes. The interaction between RAGE and advanced glycation end products (AGEs) promotes gene expression, enhances the release of proinflammatory molecules and causes the generation of oxidative stress in numerous cell types. The aim of this investigation was to evaluate the effect of enalapril and losartan on RAGE expression in abdominal aortic endothelium of rats with experimentally induced diabetes. Male Sprague-Dawley rats, weighing approximately 150 - 200 g, were used. Diabetes was induced in 30 rats by intravenous administration of a single dose of 55 mg/kg body weight of streptozotocin (ETZ). The following groups were studied: control (n=10), diabetic (n=10), losartan-treated diabetic (n=10) and enalapril-treated diabetic (n=10) rats. RAGE expression in aortic endothelium was determined by indirect immunofluorescence. A significant increase in RAGE expression was observed in diabetic animals versus controls (p<0.001), there was a decrease in RAGE expression, in animals treated with losartan versus controls (p<0.01) and in those treated with enalapril (p<0.05) versus control and versus diabetes + vehicle. In conclusion, in the experimental model of ETZ-induced diabetes, there is an increase in RAGE expression at the level of the abdominal aortic endothelium, which can be reversed by treatment with losartan and/or enalapril, two drugs that block the renin-angiotensin system, suggesting its involvement in the molecular events related to vascular damage during diabetes.

El receptor para productos finales de glicación avanzada (RAGE) está implicado en la patogénesis de varias enfermedades crónicas incluyendo la diabetes. La interacción entre RAGE y los productos finales de glicación avanzada (AGEs), promueve la expresión génica, potencia la liberación de moléculas proinflamatorias y provoca la generación de estrés oxidativo en numerosos tipos de células. El objetivo de esta investigación fue evaluar el efecto del enalapril y el losartán sobre la expresión de RAGE en el endotelio de la aorta abdominal de ratas con diabetes inducida experimentalmente. Se utilizaron ratas Sprague-Dawley machos, con un peso aproximado de entre 150 - 200 g. La diabetes se indujo en 30 ratas mediante la administración intravenosa de una sola dosis de 55 mg/Kg de peso corporal de estreptozotocina (ETZ). Se estudiaron los siguientes grupos: ratas control (n=10), diabéticas (n=10), diabéticas tratadas con losartán (n=10) y diabéticas tratadas con enalapril (n=10). La expresión de RAGE en el endotelio aórtico se determinó por inmunofluorescencia indirecta. Se observó un incremento significativo en la expresión de RAGE en los animales diabéticos versus los controles (p<0.001), hubo una disminución en la expresión de RAGE, en los animales tratados con losartán versus los controles (p<0.01) y en los tratados con enalapril (p<0.05) versus control y versus diabetes + vehículo. En conclusión, en el modelo experimental de diabetes inducida por ETZ, existe un incremento en la expresión de RAGE a nivel del endotelio de la aorta abdominal, la cual puede revertirse mediante el tratamiento con losartán y/o enalapril, dos fármacos bloqueadores del sistema renina-angiotensina, lo cual sugiere la participación del mismo en los acontecimientos moleculares relacionados con el daño vascular durante la diabetes.

Metformin and resveratrol suppress type 2 diabetes mellitus-induced articular cartilage damage in rats associated with the inhibition of inflammation and augmentation of proteoglycans / La metformina y el resveratrol suprimen el daño del cartílago articular inducido por la diabetes mellitus tipo 2 en ratas asociado con la inhibición de la inflamación y el aumento de proteoglicanos

SUMMARY: Induction of osteoarthritis (OA) following diabetes is characterized by a sever inflammation of the joints that can lead to disability. The cartilage content of proteoglycans can substantially be reduced, following the induction of diabetes mellitus associated with inflammation as well as knee joint injury, and the antidiabetic drug metformin combined with the anti-inflammatory agent resveratrol can prevent these deleterious effects. Therefore, insulin-independent diabetes, type 2 diabetes mellitus (T2DM) was induced in Albino rats by streptozotocin (STZ) injection (50 mg/kg) after being fed on a high carbohydrate and fat diets for 2 weeks. The protective group of rats which also received a single injection of STZ was treated daily with metformin (Met; 200 mg/kg) and resveratrol (Res; 30 mg/kg) for 12 weeks. Harvested knee joint tissues were prepared for basic histology stain and for proteoglycans staining using light microscopy. Histology images showed in diabetic rats (T2DM) OA development as demonstrated by profound injury to the knee joint and severe decrease of articular cartilage proteoglycans content, which were substantialy protected by Met+Res. Met+Res also significantly (p< 0.0001) decreased diabetes induced glycemia, dyslipidemia, and the inflammatory biomarkers, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high sensitivity C-reactive protein (hs-CRP). In addition, there was a significant correlation between OA and glycemia, dyslipidemia, and inflammation. Collectively, we demonstrate an association between knee joint damage and biomarkers of glycemia, dyslipidemia, and inflammation in diabetes-induced OA, with metformin plus resveratrol providing protective effects.

RESUMEN: La inducción de osteoartritis (OA) después de la diabetes se caracteriza por una inflamación severa de las articulaciones que puede conducir a la discapacidad. El contenido de cartílago de proteoglicanos se puede reducir sustancialmente, luego de la inducción de diabetes mellitus asociada con inflamación y lesión en la articulación de la rodilla sin embargo, el fármaco antidiabético metformina combinado con el agente antiinflamatorio resveratrol puede prevenir estos efectos nocivos. Por lo tanto, se indujo diabetes insulino dependiente, diabetes mellitus tipo 2 (T2DM) en ratas albinas mediante inyección de estreptozotocina (STZ) (50 mg/kg) después de haber sido alimentadas con dietas ricas en carbohidratos y grasas durante 2 semanas. El grupo protector de ratas que también recibió una inyección única de STZ fue tratado diariamente con metformina (Met; 200 mg/kg) y resveratrol (Res; 30 mg/kg) durante 12 semanas. Tejidos de la articulación de la rodilla fueon retirados y teñidos con histología básica y tinción de proteoglicanos usando microscopía óptica. Las imágenes histológicas en ratas diabéticas mostraban (T2DM) desarrollo de OA visualizadas por una lesión profunda en la articulación de la rodilla y una disminución severa del contenido de proteoglicanos del cartílago articular, los cuales estaban sustancialmente protegidos por Met+Res. Met+Res. También disminuyó significativamente (p< 0,0001) la glucemia inducida por la diabetes, la dislipidemia y los biomarcadores inflamatorios, el factor de necrosis tumoral alfa (TNF-α), la interleucina-6 (IL-6) y la proteína C reactiva de alta sensibilidad (PCR-hs). Además, hubo una correlación significativa entre la OA y la glucemia, la dislipidemia y la inflamación. En conjunto, demostramos una asociación entre el daño de la articulación de la rodilla y los biomarcadores de glucemia, dislipidemia e inflamación en la OA inducida por diabetes, con metformina más resveratrol que brindan efectos protectores.

Pouteria ramiflora leaf extract on emulgel in wound healing activity in diabetic rats / Ação do extrato de folhas de Pouteria ramiflora em emulgel na atividade de cicatrização de feridas em ratos diabéticos

The genus Pouteria has been studied because it presents various activities, among which is its anti-inflammatory potential. The effects of Pouteria ramiflora Carbopol gel on the healing of skin wounds in diabetic rats were evaluated by microscopic imaging. Streptozotocin was administered intraperitoneally in animals that had fasted for 12 hours, a situation confirmed by the glycemic index (> 240 mg dL-1). An excision on the back of the animals was performed and three groups were formed: Control (Gel), Ethanolic extract (Ext) and Gel + extract 2% (Ext+gel); the histopathological evaluation occurred on the 7th, 14th, 21st and 30th days after the post-operative period. The results of the phytochemical prospecting of P. ramiflora extract demonstrated the major presence of phenolic compounds and flavonoids; the assessment of the inflammatory infiltrate on the 7th day was higher on group Ext and Ext+gel when compared to group Control; on the 14th day control and Ext (p<0.05). The quantification of fibroblasts was higher on the 7th day among the three treatments, control and Ext (p<0.05), on the 21st day. Angiogenesis showed a higher number of vessels in Ext+gel group (p<0.05) on the 7th day; in Control, Ext and Ext+gel (p<0.05) on the 14th day; and Control and Ext (p<0.05)on the 21st day. The histopathological results showed that the formulation Ext+gel was efficient in tissue reparation and decrease in inflammatory cells on the diabetic's animals.

O gênero Pouteria apresenta várias aplicações terapêuticas e, dentre elas, grande potencial antiflamatório. Os efeitos do gel de Pouteria ramiflora sobre a cicatrização de feridas na pele de ratos diabéticos foram avaliados pela histomorfometria. A estreptozotocina foi administrada por via intraperitoneal em animais após jejum de 12 horas, a confirmação de indução da diabetes foi confirmada pelo índice glicêmico (> 240 mg dL-1). Foi realizada uma incisão no dorso do animal e foram criados 3 grupos de tratamento: controle (gel carbopol), extrato etanólico (Ext) e Gel + extrato etanólico à 2% (Ext+gel); a avaliação histopatológica foi realizada no 7º, 14º, 21º e 30º dias após o período pós operatório. Os resultados da prospecção fitoquímica dos extratos de P. ramiflora demonstraram majoritariamente a presença de compostos fenólicos e flavonóides; o infiltrado inflamatório avaliado no 7º dia foi maior para animais do grupo controle em relação aos grupos Ext (p<0.05) e Ext+gel 2% (p<0.05); no 14º dia o controle e Exp (p<0.05) apresentaram aumento significativo dos infiltrados inflamatórios. A presença de fibroblastos foi elevada no 7º dia em todos os tratamentos. O processo da angiogênese mostrou um maior número de vasos sanguíneos entre os grupos Ext e Ext+gel (p<0.05) no 7º dia; no 14º dia o grupo controle, Ext (p<0.05), Control e Ext+gel (p<0.05) apresentaram aumento de vascularização, e no 21º dia apenas os grupos controle e Ext (p<0.05). Os resultados histopatológicos mostraram que a formulação gel carbopol + extrato etanólico a 2% foi eficiente na reparação de tecidos e na diminuição de células inflamatórias nos animais diabéticos.

Analysis of high-intensity interval training on bone mineral density in an experimental model of type 2 diabetes

Purpose: To analyze the effect of high-intensity interval training (HIIT) on bone mineral density (BMD) in a model of type 2 diabetes mellitus. Methods: Thirty-two male, adult, 12-week-old rats (Rattus norvegicus), of the Wistar lineage, were used. The animals induced to the experimental model received a high fat diet for 10 days and, after that period, intraperitoneal injection of streptozotocin (40 mg·kg­1), dissolved in 20 mmol·L­1 sodium citrate solution (pH = 4.5). The experimental group of diabetes was formed by the animals that, 48 h after the injection of streptozotocin, had fasting blood glucose > 250 mg·dL­1). The animals were randomly divided into four groups with eight animals each: HIIT experimental diabetes; HIIT control; sedentary experimental diabetes and sedentary control. The animals in the HIIT group performed an aerobic exercise protocol on a treadmill inclined at an angle of 15° to the horizontal, with interspersed intensity. Five weekly sessions, lasting 49 min each, were held for 6 weeks. The analysis of cortical bone density (CBD) and BMD were performed by X-ray images using the In-Vivo Xtreme II/Bruker system. Results: For CBD and BMD, when comparing diabetes and control groups, a significant difference was seen between groups in relation to HIIT (p = 0.007). Animals submitted and not submitted to HIIT in the same group showed a significant difference between groups in relation to diabetes (p < 0.001). Conclusions: The HIIT experimental diabetes group had increased CBD and BMD in comparison with the sedentary experimental diabetes group.

Insulin replacement prevents the acquisition but not the expression of morphine-induced conditioned place preference in streptozotocin-induced diabetic rats

Abstract Insulin receptors have distributed in all brain regions, including the nucleus Accumbens (NAc), and where is implicated in the reward properties of drugs. It is well known that insulin signaling can regulate dopamine release. Therefore, in the present study, we tried to examine the effect of insulin replacement on the acquisition and expression of morphine-induced conditioned place preference (CPP) in diabetic rats. Forty-eight male Wistar rats were divided into two non-diabetic (Naïve) and diabetic groups rendered by a single injection of streptozotocin (STZ). These groups separately received insulin (10U/kg) or saline (1 ml/kg) one hour prior to morphine administration (5mg/kg;s.c.) during conditioning days (acquisition phase) or post-conditioning day (expression phase) in the CPP paradigm. In this paradigm, conditioning score (CS) and locomotion activity were recorded by Ethovision. The STZ-induced diabetic rats displayed higher CS compared to naïve rats (P<0.05). This effect was abolished in all diabetic rats that received insulin during conditioning days but not the expression phase. This study has provided evidence that insulin plays a modulatory role in morphine-induced CPP, and insulin replacement during the acquisition phase could reduce the rewarding properties of morphine in diabetes conditions through a possible modulating effect on dopamine release in the NAc region

Free interstitial levels of metformin in the liver of healthy and diabetic Wistar rats

Abstract In the present study, free interstitial levels reached by metformin in the liver were investigated in control and diabetic rats by microdialysis. Firstly, a bioanalytical method using an HPLC-UV system to determine the drug concentration in microdialysis samples was validated. The blood glucose levels and biochemical parameters were investigated in control and diabetic animals. Following that, both groups received a dose of 50 mg/kg of metformin iv bolus and the free interstitial levels reached in the liver were assessed by microdialysis. The method was validated according to FDA guidelines being suitable to quantify free concentrations of metformin in the liver of control and diabetics rats. Free exposure to metformin was similar in control and diabetic animals: AUC0-∞ 118.50 ± 40.18 vs 112.93 ± 50.25 µg.h/mL, respectively. The half-life in tissue was similar to that described in the literature for plasma. Hence diabetes induced by streptozotocin after administration of nicotinamide in our study did not damage the renal and hepatic function of the animals. The levels reached in the liver were 1.6 times higher than the free plasma concentrations, demonstrating higher liver penetration of metformin. This is the first investigation in liver interstitial concentration of metformin in control and diabetic rats

The effects of early diabetes on duodenal alterations in the rats / Efectos de la diabetes temprana sobre las alteraciones duodenales en ratas

SUMMARY: Diabetes mellitus (DM) mainly affects functional changes in the duodenum, which plays an important role in the digestion and absorption of food. The impairment of duodenal function contributes to malnutrition, abdominal bloating and pain in diabetic patients. Thus, this study aimed to investigate the histological alterations and quantitative measurements of duodenal structures in the early stage of streptozotocin (STZ)-induced diabetic rats. Eight male Sprague-Dawley rats were divided into three control and five diabetic rats. Diabetes was induced by a single intraperitoneal dose of 60 mg/kg STZ. After four weeks of diabetic induction, the duodenum was prepared for histological study and morphometric analysis. In diabetic rats, there were deformed villi with disrupted surface epithelium and mildly distorted shapes of crypts, together with an increase in villus height and crypt depth. The epithelial cells detached from their underlying basement membrane. The goblet cells decreased in number, whereas an increased number of Cellula panethensis (Paneth cells) with pale-stained eosinophilic granules occurred in the DM group. A diabetic thickened submucosal layer was observed as enhanced duodenal glands (Brunner's glands) hypertrophy and collagen accumulation. These findings indicated that histopathologic lesions of the duodenum developed in the early stage of diabetes. The destruction of villi, crypts, and epithelium may affect digestion and absorption. The structural changes in goblet and Cellula panethensis and duodenal glands may be associated with malfunction to protect duodenal mucosa from bacteria and stomach acid. These conditions can worsen the quality of life in diabetic individuals, leading to complications such as maldigestion, malabsorption, and duodenal ulcer.

RESUMEN: La diabetes mellitus (DM) afecta principalmente a cambios funcionales en el duodeno, que juega un papel importante en la digestión y absorción de los alimentos. El deterioro de la función duodenal contribuye a la desnutrición, distensión abdominal y dolor en pacientes diabéticos. Por lo tanto, este estudio tuvo como objetivo estudiar las alteraciones histológicas y determinar las mediciones cuantitativas de las estructuras duodenales en la etapa temprana de ratas diabéticas inducidas por estreptozotocina (STZ). Ocho ratas macho Sprague-Dawley fueron distribuidas en dos grupos: tres ratas control y cinco diabéticas. La diabetes se indujo mediante una dosis intraperitoneal única de 60 mg/kg de STZ. Después de cuatro semanas de inducción, se preparó el duodeno para estudio histológico y análisis morfométrico. En ratas diabéticas, había vellosidades deformadas con epitelio superficial destruido y formas ligeramente distorsionadas de las criptas, junto con un aumento en la altura de las vellosidades y la profundidad de las criptas. Las células epiteliales se encontraban separadas de la membrana basal subyacente. Las células caliciformes habían disminuido en número, mientras que en el grupo DM se produjo un aumento en el número de Cellula panethensis (células de Paneth) con gránulos eosinofílicos teñidos pálidos. Se observó una capa submucosa engrosada con aumento de la hipertrofia de las glándulas duodenales (glándulas de Brunner) y acumulación de colágeno. Estos hallazgos indican que las lesiones histopatológicas del duodeno se desarrollaron en la etapa temprana de la diabetes. La destrucción de vellosidades, criptas y epitelio puede afectar la digestión y la absorción. Los cambios estructurales en Cellula panethensis y glándulas duodenales pueden estar asociados con un mal funcionamiento en la protección de la mucosa duodenal tanto de las bacterias como del ácido gástrico. Estas condiciones pueden empeorar la calidad de vida de las personas diabéticas y provocar complicaciones como mala digestión, malabsorción y úlcera duodenal.

Catecholamines production by kidney tissue and mesangial cell culture is differentially modulated by diabetes / A produção de catecolaminas pelo tecido renal e a cultura de células mesangiais é modulada diferencialmente pelo diabetes

Abstract Introduction: According to the International Diabetes Federation, the number of people with diabetes mellitus may reach 700 million in 2045. Catecholamines are involved in the regulation of several kidney functions. This study investigates the effects of hyperglycemia on catecholamines' metabolism in kidney tissue from control, diabetic, and insulin-treated diabetic rats, both in vivo and in vitro. Methods: Male Wistar-Hannover rats were randomized into: control, diabetic, and insulin-treated diabetic groups. Diabetes was induced by a single injection of streptozotocin, and diabetic treated group also received insulin. After 60 days, blood and kidney tissue from all groups were collected for catecholamines' quantification and mesangial cells culture. Results: diabetic rats had lower body weight, hyperglycemia, and increase water intake and diuresis. Additionally, diabetes promoted a sharp decrease in creatinine clearance compared to control group. Regarding the whole kidney extracts, both diabetic groups (treated and non-treated) had significant reduction in norepinephrine concentration. In mesangial cell culture, catecholamines' concentration were lower in the culture medium than in the intracellular compartment for all groups. Norepinephrine, epinephrine, and dopamine medium levels were increased in the diabetic group. Conclusion: The major finding of the present study was that 8 weeks of diabetes induction altered the kidney catecholaminergic system in a very specific manner, once the production of catecholamines in the excised kidney tissue from diabetic rats was differentially modulated as compared with the production and secretion by cultured mesangial cells.

Resumo Introdução: Segundo a Federação Internacional de Diabetes, o número de pessoas com diabetes mellitus pode chegar a 700 milhões em 2045. As catecolaminas estão envolvidas na regulação de várias funções renais. Este estudo investiga os efeitos da hiperglicemia no metabolismo das catecolaminas no tecido renal de ratos controle, diabéticos e diabéticos tratados com insulina, tanto in vivo como in vitro. Métodos: Os ratos Wistar-Hannover machos foram randomizados em: grupos controle, diabéticos e diabéticos tratados com insulina. O diabetes foi induzido por uma única injeção de estreptozotocina, e o grupo diabético tratado também recebeu insulina. Após 60 dias, sangue e tecido renal dos grupos foram coletados para quantificação de catecolaminas e cultura de células mesangiais. Resultados: ratos diabéticos apresentaram peso corporal mais baixo, hiperglicemia, e aumento da ingestão de água e diurese. Ademais, o diabetes promoveu uma redução acentuada na depuração de creatinina comparado com o grupo controle. Quanto aos extratos de rim total, ambos os grupos diabéticos (tratados/não tratados) tiveram redução significativa na concentração de noradrenalina. Na cultura de células mesangiais, a concentração de catecolaminas foi menor no meio de cultura do que no compartimento intracelular para todos os grupos. Níveis médios de noradrenalina, adrenalina e dopamina estavam aumentados no grupo diabético. Conclusão: O principal achado deste estudo foi que 8 semanas de indução de diabetes alteraram o sistema catecolaminérgico renal de maneira muito específica, já que a produção de catecolaminas no tecido renal excisado de ratos diabéticos foi modulada diferencialmente comparada com produção e secreção por células mesangiais cultivadas.

Novo Efeito Cardioprotetor da L-Carnitina em Camundongos Obesos Diabéticos: Regulação da Expressão de Quemerina e CMKLRI no Coração e Tecidos Adiposos / Novel Cardioprotective Effect of L-Carnitine on Obese Diabetic Mice: Regulation of Chemerin and CMKLRI Expression in Heart and Adipose Tissues

Resumo Fundamentos A L-carnitina (LC) tem muitos efeitos benéficos em animais diabéticos e humanos, mas seu efeito regulatório sobre a quemerina como uma citocina inflamatória e seu receptor no estado diabético são desconhecidos. Objetivos O presente estudo teve como objetivo investigar o efeito regulatório da LC na expressão do receptor semelhante ao de quimiocina 1 e quemerina (CMKLRI) em tecidos adiposo e cardíaco de camundongos diabéticos. Métodos Sessenta camundongos NMARI foram divididos em quatro grupos, incluindo controle, diabético, diabético + suplementação com LC e controle + suplementação com LC. O diabetes foi induzido pela alimentação dos animais com dieta hipercalórica por 5 semanas e injeção de estreptozotocina. Os animais foram tratados com 300 mg/kg de LC por 28 dias. Nos dias 7, 14 e 28 após o tratamento, os níveis de mRNA e proteína da quemerina e CMKLRI nos tecidos cardíacos e adiposos de animais foram determinados utilizando análise por qPCR e ELISA. Os índices de resistência à insulina também foram medidos em todos os grupos experimentais. A diferença com p<0,05 foi considerada significativa. Resultados A expressão de quemerina e CMKLRI aumentou nos tecidos cardíaco e adiposo de camundongos diabéticos nos dias 14 e 28 após a indução do diabetes, concomitantemente com a incidência de resistência à insulina e níveis aumentados de quemerina circulante (p<0,05). O tratamento com LC causou uma diminuição significativa na expressão de ambos os genes nos tecidos estudados e redução dos sintomas de resistência à insulina e dos níveis séricos de quemerina (p<0,05). Conclusão Os resultados sugerem que o tratamento com LC pode diminuir a expressão de quemerina e CKLR1 em tecidos cardíacos e adiposos de animais experimentais obesos e diabéticos.

Abstract Background L-carnitine (LC) has many beneficial effects on diabetic animals and humans, but its regulatory effect on chemerin as an inflammatory cytokine, and its receptor in diabetes status is unknown. Objectives The present study aimed to investigate the regulatory effect of LC on the expression of chemerin and chemokine-like receptor I (CMKLRI) in adipose and cardiac tissues of diabetic mice. Methods Sixty NMARI mice were divided into four groups including control, diabetic, diabetic + LC supplementation and control + LC supplementation. Diabetes was induced by feeding the animals a high-calorie diet for 5 weeks and injection of Streptozotocin. The animals were treated with 300 mg/kg LC for 28 days. On days 7, 14, and 28 after treatment, the mRNA and protein levels of chemerin and CMKLRI in the cardiac and adipose tissues of the animals were determined using qPCR analysis and ELISA. Insulin resistance indices were also measured in all experimental groups. Differences with p <0.05 were considered significant. Results Chemerin and CMKLRI expressions levels were increased in cardiac and adipose tissues of diabetic mice on days 14 and 28 after diabetes induction, concurrent with the incidence of insulin resistance and increased levels of circulating chemerin (p<0.05). The treatment with LC caused a significant decrease in the expression of both genes in studied tissues and the reduction of insulin resistance symptoms and serum chemerin levels (p<0.05). Conclusion The results suggest that LC treatment were able to downregulate the expression of chemerin and CKLR1 in cardiac and adipose tissues of obese, diabetic experimental animals.

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)

Malformaciones esqueléticas y alteraciones del crecimiento en fetos de ratas con diabetes moderada / Skeletal malformations and growth disturbances in fetuses of mild diabetic rats

Resumen Introducción. En la actualidad, la diabetes mellitus representa una de las condiciones médicas que complica el embarazo con mayor frecuencia, lo que afecta el crecimiento y el desarrollo fetal. Objetivo. Determinar las malformaciones esqueléticas y alteraciones en el crecimiento en fetos de ratas Wistar diabéticas. Materiales y métodos. Se utilizó un modelo de diabetes moderada inducida neonatalmente con estreptozotocina (STZ 100 mg/kg de peso corporal, por vía subcutánea) en ratas Wistar. En la adultez, las ratas sanas y diabéticas se aparearon con machos sanos de la misma edad y cepa. El día 20 de gestación se practicó la cesárea bajo anestesia. Se extrajeron los fetos, se pesaron y clasificaron como pequeños (PAG), adecuados (AEG) o grandes (GEG) para la edad gestacional. Los fetos seleccionados se procesaron para el análisis de anomalías esqueléticas y sitios de osificación. Resultados. En la descendencia de las ratas diabéticas, hubo un mayor porcentaje de fetos clasificados como pequeños o grandes y un menor porcentaje de fetos con peso adecuado; el promedio de peso fetal fue menor y había menos sitios de osificación. Se observaron alteraciones en la osificación de cráneo, esternón, columna vertebral, costillas y extremidades anteriores y posteriores; y también, hubo una correlación directa entre el peso y el grado de osificación fetal. Hubo malformaciones congénitas asociadas con la fusión y bifurcación de las costillas, así como cambios indicativos de hidrocefalia, como la forma de domo del cráneo, una amplia distancia entre los parietales y la anchura de las fontanelas anterior y posterior. Conclusión. La diabetes moderada durante la gestación altera el crecimiento y el desarrollo fetal, que se ve afectado tanto por macrosomía y la restricción del crecimiento intrauterino como por malformaciones esqueléticas.

Abstract Introduction: Currently, diabetes mellitus represents one of the medical conditions that more frequently complicates pregnancy affecting the fetus's growth and development. Objective: To determine the skeletal malformations and growth alterations in fetuses of diabetic Wistar rats. Materials and methods: We used a neonatally streptozotocin-induced mild diabetes model (STZ 100 mg/kg body weight - subcutaneously) in Wistar rats. In adulthood, healthy and diabetic rats were mated with healthy males of the same age and strain. On day 20 of gestation, a cesarean was performed under anesthesia. Fetuses were removed, weighed, and classified as small (SPA), adequate (APA), and large (LPA) for the gestational age. Selected fetuses were processed for skeletal anomaly and ossification sites analysis. Results: In the offspring of diabetic rats, there was a higher percentage of fetuses classified as small or large and a lower percentage of fetuses with adequate weight; the fetal weight mean was lower and there were fewer sites of ossification. Alterations were observed in the ossification of the skull, sternum, spine, ribs and fore and hind limbs; and also, there was a direct correlation between fetal weight and ossification degree There were congenital malformations associated with fusion and bifurcation of the ribs, as well as changes indicative of hydrocephaly, such as the dome shape of the skull, a wide distance between parietals, and the width of the anterior and posterior fontanels. Conclusion: Moderate diabetes during pregnancy alters fetal growth and development with macrosomia and intrauterine growth restriction, as well as skeletal malformations.