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

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.

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.

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.

Prevention of Teratogenesis in Pregnancies of Obese Rats by Vitamin E Supplementation.

Congenital malformations are a common adverse outcome in pregnancies complicated by pregestational obesity, although the underlying mechanisms are still unrevealed. Our aim was to study the effect of oxidative stress in obesity-induced teratogenesis. Wistar rats were fed a high-fat diet for 13 weeks, with (OE group) or without (O group) vitamin E supplementation. Then, rats were mated and sacrificed at day 11.5 of gestation. Embryos from O dams presented a 25.9 ± 3.5% rate of malformations (vs. 8.7 ± 3.4% in C rats), which was reduced in the OE group (11.5 ± 2.3%). Pregestational obesity induced hepatic protein and DNA oxidation and a decline in antioxidant enzymes. Importantly, glutathione content was also decreased, limiting the availability of this antioxidant in the embryos. Vitamin E supplementation efficiently maintained glutathione levels in the obese mothers, which could be used in their embryos to prevent oxidation-induced malformations. To test the effect of decreasing glutathione levels alone in a cell culture model of neuroepithelium, murine embryonic stem cells (ESC) were induced to form neuronal precursors and glutathione synthesis was inhibited with the gamma-glutamylcysteine synthesis inhibitor, buthionine sulfoximine (BSO). BSO inhibited the expression of Pax3, a gene required for neural tube closure that is also inhibited by oxidative stress. Taken together, our data indicate that obesity causes malformations through the depletion of maternal glutathione, thereby decreasing glutathione-dependent free radical scavenging in embryos, which can be prevented by vitamin E supplementation.

Experimental diabetes impairs maternal reproductive performance in pregnant Wistar rats and their offspring.

The aim of this study was to determine the effect of mild hyperglycemia on metabolism during pregnancy, the maternal reproductive performance, and the characteristics of the offspring in neonatal mild diabetic-induced Wistar rats. The experimental diabetes model was generated by neonatal streptozotocin administration (100 mg of streptozotocin/Kg bw/sc) in female Wistar rats. At adulthood, the control and diabetic group were mated. At the 20th day of gestation, a maternal and fetal blood sample were collected for biochemical measurement. The maternal livers, fetal livers, and placenta were removed for oxidative stress measurements. Maternal reproductive outcomes and fetal and placental morphometric measurements were analyzed. The fetuses were classified as small, appropriate, and large for pregnancy age, and examined for the presence of external anomalies. The diabetic group showed mild hyperglycemia, altered glucose tolerance, increased total cholesterol, triglycerides, and hemoglobin A1c during pregnancy. At the 20th day of gestation the diabetic mothers presented increased reabsorptions and embryonic losses before and after implantation, reduced corpora lutea number, litter size, implantation sites, live fetuses, and decreased efficiency of implantation rate. Similarly, the offspring showed reduced fetal, craniofacial, and placental dimensions, in addition to a higher proportion of small fetuses for pregnancy age. Mild hyperglycemia during pregnancy did not generate marked oxidative stress in the mother, and in fetal liver and placenta decreased antioxidant activity was evident by significant consumption of reduced glutathione. Mild diabetes led to a negative impact on maternal reproductive performance and characteristics of the offspring. This experimental model reproduced maternal and fetal outcomes of pregnant rats presenting controlled diabetes. ABBREVIATIONS: bw: body weight; sc: subcutaneous; DM: diabetes mellitus; STZ: streptozotocin; OGTT: oral glucose tolerance test; ITT: insulin tolerance test; GSH: glutathione; MDA: malondialdehyde; AOPPs: advanced oxidation protein products; TBARs: thiobarbituric acid reaction; SPA: small for pregancy age; APA: appropriate for pregnancy age; LPG: large for pregnancy age; ROS: reactive oxygen species.

Vascular Dysfunction in Mother and Offspring During Preeclampsia: Contributions from Latin-American Countries.

Pregnancy is a physiologically stressful condition that generates a series of functional adaptations by the cardiovascular system. The impact of pregnancy on this system persists from conception beyond birth. Recent evidence suggests that vascular changes associated with pregnancy complications, such as preeclampsia, affect the function of the maternal and offspring vascular systems, after delivery and into adult life. Since the vascular system contributes to systemic homeostasis, defective development or function of blood vessels predisposes both mother and infant to future risk for chronic disease. These alterations in later life range from fertility problems to alterations in the central nervous system or immune system, among others. It is important to note that rates of morbi-mortality due to pregnancy complications including preeclampsia, as well as cardiovascular diseases, have a higher incidence in Latin-American countries than in more developed countries. Nonetheless, there is a lack both in the amount and impact of research conducted in Latin America. An impact, although smaller, can be seen when research in vascular disorders related to problems during pregnancy is analyzed. Therefore, in this review, information about preeclampsia and endothelial dysfunction generated from research groups based in Latin-American countries will be highlighted. We relate the need, as present in many other countries in the world, for increased effective regional and international collaboration to generate new data specific to our region on this topic.

Concentration of Zinc, Copper, Iron, Calcium, and Magnesium in the Serum, Tissues, and Urine of Streptozotocin-Induced Mild Diabetic Rat Model.

The present study aimed to investigate, in the streptozotocin-induced mild diabetic rat model, the zinc (Zn), copper (Cu), iron (Fe), calcium (Ca), and magnesium (Mg) concentration in serum, liver, and kidney tissues, and urine samples from adult Wistar rats treated neonatally with streptozotocin (STZ). Diabetes was induced by subcutaneous administration of streptozotocin (100 mg/Kg) in female Wistar rats of 2 days old (STZ, n = 10). Control group (CG, n = 10) received only sodium-citrate buffer. The mineral concentrations were measured by atomic absorption spectrophotometry. The validity and accuracy were checked by conventional methods. STZ neonatal injection successfully leaded to mild diabetes in the adult rats. Serum concentrations of Zn, Cu, Fe, Ca, and Mg showed no changes (p > 0.05) due to diabetes. The Zn, Fe, Ca, and Mg concentrations in liver and kidney tissues were not different (p > 0.05) between STZ and CG. The mean values of Cu were higher (p < 0.05) in liver and kidney samples from STZ as compared to CG. Urine minerals concentrations (Zn, Cu, Fe and Ca) in STZ-rats group were lower (p < 0.05) than CG. However, the content of all evaluated minerals in the excreted urine were higher (p < 0.01) in STZ-rats during a 24 h collection period. Urinary excretion of Zn, Cu, Fe, Ca, and Mg was strongly correlated with urinary volume during the 24 h period (r > 0.7; p < 0.001). Observed changes in mineral metabolism of STZ-induced mild diabetes model could be due to the endocrine imbalance associated with the diabetic condition.

Streptozotocin diabetogenic action in an experimental neonatal induction model.

INTRODUCTION: The use of experimental models is essential to study the pathophysiological mechanisms of diabetes.  OBJECTIVES: To compare in adult Wistar rats the diabetogenic action of streptozotocin according to the moment and route of administration during the neonatal period by evaluating biochemical, metabolic and histological variables.  MATERIALS AND METHODS: Eight groups of neonatal female Wistar rats (n=10) were formed. We evaluated the induction with streptozotocin (100 mg/kg of body weight) on days 2 and 5 after birth, as well as the administration routes (subcutaneous or intraperitoneal). Controls were injected with sodium citrate buffer. Blood glucose level, body weight, food and water intake were monitored for 12 weeks. We also performed tolerance tests for oral glucose and glycosylated hemoglobin, and a histopathological pancreas morphometric study.  RESULTS: The mortality rate was about 100% among rats given streptozotocin on their fifth day of life. All rats receiving the drug on day 2 of life survived, and they showed a marked hyperglycemia, polyphagia, polydipsia and decreased body weight gain in addition to increased glycosylated hemoglobin rates and impaired results in the oral glucose tolerance test. Histopathological lesions of the pancreas as well as a decreased number of islets were significantly more frequent in rats receiving the drug subcutaneously on day 2, which confirms that streptozotocin administered subcutaneously produces greater damage.  CONCLUSIONS: Subcutaneous injection of streptozotocin in a dose of 100 mg/kg of body weight in the second day after birth induced moderate diabetes in adult Wistar rats more effectively.

Acción de la estreptozotocina en un modelo experimental de inducción neonatal de la diabetes / Streptozotocin diabetogenic action in an experimental neonatal induction model

Introducción. El estudio de la diabetes mediante modelos experimentales es fundamental para entender los mecanismos fisiopatológicos de la enfermedad. Objetivos. Comparar en ratas Wistar adultas la acción de inducción de la diabetes de la estreptozotocina según el momento y la vía de inoculación del fármaco durante el periodo neonatal mediante la evaluación de variables bioquímicas, metabólicas e histológicas. Materiales y métodos. Se conformaron ocho grupos con ratas Wistar hembras recién nacidas (n=10). Se evaluó la inducción con estreptozotocina (100 mg/kg de peso corporal) según el día (segundo y quinto después del nacimiento) y la vía de inoculación (subcutánea o intraperitoneal). Los controles se inyectaron con solución tampón de citrato sódico. Durante 12 semanas se evaluaron la glucemia, el peso, y la cantidad de alimento y de agua consumida. Se hicieron pruebas de tolerancia a la glucosa oral, se evaluó la hemoglobina ´glicosilada´, y se hizo el estudio morfométrico e histopatológico del páncreas. Resultados. Casi todos los animales inoculados con estreptozotocina en el quinto día murieron, en tanto que todos los inoculados en el segundo día sobrevivieron. La administración subcutánea de estreptozotocina en el segundo día produjo hiperglucemia, polifagia, polidipsia y disminución de la ganancia de peso corporal, así como alteración de los valores de hemoglobina ´glicosilada´ y en la prueba de tolerancia a la glucosa. Las lesiones histopatológicas del páncreas, así como la disminución del número de islotes, se observaron con mayor frecuencia con la estreptozotocina aplicada de forma subcutánea en el segundo día, lo cual corroboró que el efecto de este agente inoculado de forma subcutánea causa mayor daño. Conclusiones. La inyección subcutánea de una dosis de 100 mg/kg de estreptozotocina en el segundo día después del nacimiento logró mayor efectividad en la inducción de diabetes moderada en ratas Wistar adultas.

Introduction: The use of experimental models is essential to study the pathophysiological mechanisms of diabetes. Objectives: To compare in adult Wistar rats the diabetogenic action of streptozotocin according to the moment and route of administration during the neonatal period by evaluating biochemical, metabolic and histological variables. Materials and methods: Eight groups of neonatal female Wistar rats (n=10) were formed. We evaluated the induction with streptozotocin (100 mg/kg of body weight) on days 2 and 5 after birth, as well as the administration routes (subcutaneous or intraperitoneal). Controls were injected with sodium citrate buffer. Blood glucose level, body weight, food and water intake were monitored for 12 weeks. We also performed tolerance tests for oral glucose and glycosylated hemoglobin, and a histopathological pancreas morphometric study. Results: The mortality rate was about 100% among rats given streptozotocin on their fifth day of life. All rats receiving the drug on day 2 of life survived, and they showed a marked hyperglycemia, polyphagia, polydipsia and decreased body weight gain in addition to increased glycosylated hemoglobin rates and impaired results in the oral glucose tolerance test. Histopathological lesions of the pancreas as well as a decreased number of islets were significantly more frequent in rats receiving the drug subcutaneously on day 2, which confirms that streptozotocin administered subcutaneously produces greater damage. Conclusions: Subcutaneous injection of streptozotocin in a dose of 100 mg/kg of body weight in the second day after birth induced moderate diabetes in adult Wistar rats more effectively.

Oxidative stress and birth defects in infants of women with pregestational diabetes.

Hyperglycemia characteristic of diabetes mellitus triggers pathological processes in fetal development of various structures such as the retina, peripheral nerves, renal glomerulus, and arterial and venous beds. Women with diabetes prior to conception have children with birth defects three to five times more frequently than women without diabetes. There is no specific pattern of birth defects, but the central nervous and cardiovascular systems are the most affected. Hyperglycemia leads to mitochrondrial superoxide radical production, which activates five metabolic pathways that mediate damage leading to diabetic embryopathy. Once oxidative stress is established, there is modification of gene expression controlling embryonic development in critical periods. Vitamin E application in animal models has greatly lowered occurrence of birth defects in embryonic and fetal stages, consistent with an etiologic role for oxidative stress in dysmorphogenesis. Effective metabolic control before and during pregnancy, achieved in Cuba by implementing programs for control of birth defects in children of diabetic pregnant women, has been found effective.

Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), a reliable oxidative stress marker in hypertension.

UNLABELLED: The potential use of oxidative stress products as disease markers and progression is an important aspect of biomedical research. In the present study, the quantification of urine 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) concentration has been used to express the oxidation status of hypertensive subjects. 8-oxo-dG has been simultaneously isolated and assayed in nuclear (nDNA) and mitochondrial DNA (mtDNA). In addition, oxidative stress of mononuclear cells has been estimated by means of GSH and GSSG levels and GSSG/GSH ratio in hypertensive subjects before and after antihypertensive treatment. It is shown that oxidative stress decreases significantly in hypertensive patients after treatment the effect being accompanied by reduction of their blood pressure. A significant correlation is observed comparing the yield of urine 8-oxo-dG and that isolated from mitochondria DNA. Moreover, urinary excretion of 8-oxo-dG also correlates with the GSSG/GSH ratio of cells. CONCLUSION: urine 8-oxo-dG assay is a good marker for monitoring oxidative stress changes in hypertensives.

Peroxidación lipídica y otros indicadores de estrés oxidativo en pacientes diabéticos / Lipid peroxidation and other indicators of oxidative stress in diabetic patients

Se demostró una importante relación entre los niveles de peroxidación lipídica y el desarrollo de complicaciones, en la enfermedad de origen endocrino diabetes mellitus. En este tra-bajo se encontraron variaciones en la concentración de productos de peroxidación lipídica (malonildialdehído), con valores de 8,33 ñ 2,90 en pacientes diabéticos contra 4,51 ñ 1,40 en las personas sanas. Los niveles de glutatión reducido, un antioxidante endógeno medido en suero de pacientes diabéticos demostró valores más bajos, 4,75 ñ 2,31 y 8,30 ñ 1,52 nmol/mL en suero de donantes de sangre. Se encontró una disminución significativa de la enzima catalasa, con valores de 16,21 ñ 18,25 contra 65,78 ñ 24,78 U/mL. No resultó significativa la disminución en la actividad de la enzima superóxido dismutasa

Peroxidación lipídica y otros indicadores de estrés oxidativo en pacientes diabéticos / Lipid peroxidation and other indicators of oxidative stress in diabetic patients

Se demostró una importante relación entre los niveles de peroxidación lipídica y el desarrollo de complicaciones, en la enfermedad de origen endocrino diabetes mellitus. En este tra-bajo se encontraron variaciones en la concentración de productos de peroxidación lipídica (malonildialdehído), con valores de 8,33 ñ 2,90 en pacientes diabéticos contra 4,51 ñ 1,40 en las personas sanas. Los niveles de glutatión reducido, un antioxidante endógeno medido en suero de pacientes diabéticos demostró valores más bajos, 4,75 ñ 2,31 y 8,30 ñ 1,52 nmol/mL en suero de donantes de sangre. Se encontró una disminución significativa de la enzima catalasa, con valores de 16,21 ñ 18,25 contra 65,78 ñ 24,78 U/mL. No resultó significativa la disminución en la actividad de la enzima superóxido dismutasa(AU)