Protective Effect of Total Lignans of Arctii Fructus on Retina in Rat Model of Type 2 Diabetes Mellitus / 中国实验方剂学杂志

ObjectiveTo investigate the protective effect of total lignans of Arctii Fructus on the retinal tissue in the rat model of type 2 diabetes mellitus. MethodWistar rats were randomized into normal， model， solvent， Shuangdan Mingmu Capsules （618 mg·kg-1）， and low-， medium-， and high-dose （100， 200， 400 mg·kg-1， respectively） total lignans of Arctii Fructus groups， with 16 rats in each group. The rat model was established by streptozotocin （STZ） combined with a high-fat diet and administrated with corresponding drugs by gavage once a day for 14 weeks. At the 14th week， blood was sampled for the collection of serum from the abdominal aorta after anesthesia， and bilateral eyeballs were collected and frozen. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of the retinal tissue in rats. The pathological changes of retinal vascular network in rats were observed by retinal vascular tissue digestion and mounting The levels of vascular endothelial growth factor （VEGF）， tumor necrosis factor-α （TNF-α）， and intercellular adhesion molecule-1 （ICAM-1） in the serum were determined by the ELISA kit. ResultCompared with the normal group， the solvent group showed pathological changes in the retinal tissue， reduced retinal ganglion cells （P<0.01）， and retinal thinning （P<0.01）， decreased E/P value in retinal blood vessels （P<0.01）， and elevated serum levels of VEGF， TNF-α， and ICAM-1 （P<0.01）. Compared with the model group， the total lignans of Arctii Fructus increased the retinal ganglion cells （P<0.01）， thickened the retina （P<0.01）， and lowered the serum levels of VEGF， TNF-α， and ICAM-1 （P<0.05， P<0.01）. ConclusionTotal lignans of Arctii Fructus may lower the VEGF， TNF-α， and ICAM-1 levels to protect the retina.

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.

Enhancement of caudal fin regeneration in diabetic zebrafish: An insight into proangiogenic potential of bromelain

Objectives: Diabetes mellitus is a chronic metabolic disease that is characterised by hyperglycaemia, altered lipids, carbohydrates and protein metabolism, and in the long-term, with eye, kidney, cardiovascular and neurological complications. Poor wound healing is one of the major complications faced by diabetes mellitus patients. Angiogenesis is critical for tissue regeneration and wound healing. Impaired angiogenesis may lead to poor blood flow to the wound and hence delayed wound healing. Hence, it is important to find an antidote to speed up wound healing. Hence, this study focuses on the proangiogenic potential of bromelain in the caudal fin regeneration of diabetic zebrafish. Materials and Methods: Zebrafish were divided into control, Diabetic and Diabetic + Bromelain treated groups. Diabetes mellitus was induced using multiple doses of streptozotocin (350 mg/kg b.w./i.p.) on days 1, 3, 5, 12 and 19. Glucose levels were estimated on day 21 to confirm the induction of diabetes mellitus, and then, the caudal fin was amputated. After the amputation of the caudal fin, bromelain was administered orally at a dosage of 40 mg/kg b.w. on every alternate day for 15 days. Body weight, blood glucose level, total area and percentage of fin regeneration were observed on day 36. Images were compared and areas of regeneration were analysed with the help of Image J software. One-way analysis of variance followed by Tukey’s multiple comparison tests was used to analyse the data. Results: A significant increase in the blood glucose level was observed in the diabetic group compared with control. A significant decrease in the percentage of tail regeneration and area of regeneration was observed in diabetic fishes compared to the control. Bromelain treatment has significantly increased the percentage and area of regeneration and significantly decreased the blood glucose level in the treatment group compared with the control. Conclusion: The study confirms that bromelain can promote tissue regeneration; hence, it can be used to improve wound healing, which is one of the most common complications in diabetes mellitus.

Molecular and morphological alterations in uninjured skin of streptozotocin‐induced diabetic mice

Diabetes affects every tissue in the body, including the skin. The main skin problem is the increased risk of infections, which can lead to foot ulcers. Most studies evaluating the effects of diabetes on the skin are carried out in wound healing areas. There are fewer studies on uninjured skin, and some particularities of this tissue are yet to be elucidated. In general, cellular and molecular outcomes of diabetes are increased oxidative stress and lipid peroxidation. For our study, we used C57BL/6 mice that were divided into diabetic and non-diabetic groups. The diabetic group received low doses of streptozotocin on 5 consecutive days. To evaluate the effects of hyperglycemia on uninjured skin, we performed morphological analysis using hematoxylin/eosin staining, cellular analysis using Picrosirius red and Nissl staining, and immunostaining, and evaluated protein expression by polymerase chain reaction. We confirmed that mice were hyperglycemic, presenting all features related to this metabolic condition. Hyperglycemia caused a decrease in interleukin 6 (Il-6) and an increase in tumor necrosis factor alpha (Tnf-α), Il-10, F4/80, tumor growth factor beta (Tgf-β), and insulin-like growth factor 1 (Igf-1). In addition, hyperglycemia led to a lower cellular density in the epidermis and dermis, a delay in the maturation of collagen fibers, and a decrease in the number of neurons. Furthermore, we showed a decrease in Bdnf expression and no changes in Ntrk2 expression in the skin of diabetic animals. In conclusion, chronic hyperglycemia in mice induced by streptozotocin caused disruption of homeostasis even before loss of skin continuity.

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.

Croton hirtus attenuating streptozotocin-induced neuroinflammation in rats / 数字中医药（英文）

Objective@# The present study was aimed to investigate the neuroprotective effect of Croton hirtus (CH) extract against streptozotocin (STZ) in rats. @*Methods@#(i) The sub-chronic toxicity consisted of 24 adult rats of either sex weighing from 160 to 200 g were divided into four groups with six rats in each group. Rats in group 1 received Dimethyl sulfoxide (DMSO) mixed with saline; rats in groups 2, 3, and 4 received 100, 200, and 400 mg/kg of methanolic extract of CH (MECH) orally by gavage administration for 28 d, respectively. The functional observation battery and locomotor activity were graded as part of their neurobehavioral activity and the brain regions, including cortex and hippocampus, were analyzed for neuropathological abnormalities. (ii) The main research consisted of 30 adult male Wistar rats weighing from 160 to 200 g, which were divided into five groups and six rats in each group, including control (I), STZ (II), Donepezil (III), MECH (100 mg/kg, IV), and MECH (200 mg/kg, V) groups. Rats in group I received citrate buffer orally and DMSO mixed with saline for 14 d. Rats in group II received STZ via intracerebroventricular injection (3 mg/kg, bilateral ICV-STZ) on days 1 and 3 followed by DMSO mixed with saline for 14 d. Rats in groups III, IV, and V received STZ administration on days 1 and 3 followed by Donepezil [3 mg/(kg·d), p.o.] and MECH [100 and 200 mg/(kg·d), p.o.] for 14 d. Rats were tested for learning and memory parameters such as Morris water maze (MWM) and passive avoidance test (PAT). They were sacrificed after completing behavioural experiments; brains were harvested to estimate the acetylcholinesterase (AChE), lipid peroxidation (LPO), glutathione (GSH), and superoxide dismutase (SOD) by using UV-Visible Spectrophotometer; caspase-3 was evaluated by total fluorescence emission spectra; amyloid β (Aβ) levels were detected using enzyme-linked immuosorbent assay (ELISA); and histopathological examination was conducted in the CA1 region of the hippocampus.@*Results @# (i) The sub-chronic toxicity results revealed that open field test parameters including line crossing, rearing, entering the middle square, defecating, or urinating did not differ significantly in the MECH rats (P > 0.05). The histopathological observation did not show any lesions in the neuronal cells and inflammation in both the regions in MECH rats compared with control rats. (ii) The main study findings demonstrated that STZ-treated rats showed asignificant increase in impairment in learning and memory parameters (P < 0.001), the levels of AChE, caspase-3, Aβ (1-40 and 1-42), and LPO were increased significantly (P < 0.001), and significant decrease was found in the levels of SOD (P < 0.001) and GSH (P < 0.01). Moreover, neuronal damage was found in the hippocampus. In contrast, STZ-induced behavioural and biochemical impairments in rats were considerably decreased by treatment with MECH dose-dependently. @*Conclusion@#MECH significantly prevented the memory deficit induced by STZ due to antioxidant action. Restoration of cholinergic functioning may be the cause of behavioural improvement. Therefore, MECH may be able to treat cognitive disorders like Alzheimer's disease (AD).

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.

Effect of electroacupuncture at different frequencies on brain insulin signaling transduction pathway in Alzheimer's disease mice / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) at different frequencies on learning and memory functions, as well as the relevant proteins of brain insulin signal transduction pathway in Alzheimer's disease (AD) mice and explore the effect mechanism of EA in treatment of AD.@*METHODS@#Seventy-two SPF Kunming male mice were randomized into a blank group, a sham-operation group, a model group, a 2 Hz EA group, a 15 Hz EA group and a 30 Hz EA group, 12 mice in each one. In the model group and each EA group, AD model were established by the injection with streptozotocin (ST2) solution (8 mg/kg) into the left lateral ventricles. In the sham-operation group, 0.9% sodium chloride solution of the same volume was injected into the left lateral ventricles. After successful modeling, in each EA group, EA was applied at "Baihui" (GV 20), "Dazhui" (GV 14) and "Shenshu" (BL 23) with corresponding frequencies, once daily. One course of EA intervention consisted of 7 treatments and 2 courses were given totally at interval of 1 day. After modeling and intervention, Morris water maze test was conducted for the mice of each group. Using immunohistochemistry and Western blot method, the protein expression of insulin receptor (IR), insulin receptor substrate-1 (IRS-1) and phosphatidylinositol 3-kinase (PI3K) was detected in the hippocampal of the mice after intervention.@*RESULTS@#Compared with the blank group, in the model group, the 2 Hz, 15 Hz and 30 Hz EA groups, the escape latency and the first time of crossing the platform were all extended (P<0.01), and the number of crossing the platform was reduced (P<0.01) after modeling. When compared with the blank group, the escape latency and the first time of crossing the platform were all extended (P<0.01), and the number of crossing the platform was reduced (P<0.01) in the model group after intervention. In the 2 Hz, 15 Hz and 30 Hz EA groups, the escape latency and the first time of crossing the platform were all shortened (P<0.01), and the number of crossing the platform was increased (P<0.05, P<0.01) after intervention when compared with the model group. The escape latency and the first time of crossing the platform were all shortened (P<0.01, P<0.05), and the number of crossing the platform was increased (P<0.05) in the 15 Hz and 30 Hz EA groups in comparison with the 2 Hz EA group. The protein expression levels of IR, IRS-1 and PI3K were reduced in the model group when compared with those of the blank group (P<0.01, P<0.05); and these protein expression levels were increased in the 15 Hz and 30 Hz EA groups compared with the model group (P<0.05, P<0.01). Compared with the 2 Hz EA group, the protein expression levels of IR, IRS-1 and PI3K were all elevated in the 15 Hz and 30 Hz EA groups (P<0.05).@*CONCLUSION@#The learning and memory function of AD mice may be improved through regulating brain insulin signaling transconduction pathway with electroacupuncture, and electroacupuncture at 15 Hz and 30 Hz obtains the overall better effect compared with the intervention at 2 Hz.

Embriopatía diabética y trastornos en el desarrollo reproductivo materno en ratas con diabetes pregestacional / Diabetic embryopathy and disorders in maternal reproductive development in rats with pregestational diabetes

Resumen OBJETIVOS: Determinar la repercusión de la diabetes pregestacional, con hiperglucemias moderadas, en el rendimiento reproductivo de la rata, crecimiento, desarrollo y morfología embrionaria en ratas Wistar. MATERIALES Y MÉTODOS: Estudio longitudinal, prospectivo y experimental efectuado en la Unidad de Investigaciones Biomédicas de la Universidad de Ciencias Médicas de Villa Clara, Cuba, en un modelo de diabetes moderada inducida neonatalmente a crías hembras de ratas Wistar de dos días de nacidas mediante la administración subcutánea de 100 mg/kg de peso corporal de estreptozotocina en una única dosis. A los 120 días de nacidas, las ratas de ambos grupos de experimentación (diabético y control) se aparearon con machos sanos. Se determinaron el peso y la glucemia durante la gestación y a los 11.5 días se practicó la cesárea. Se analizaron las variables del rendimiento reproductivo materno y de crecimiento, desarrollo y morfología externa en los embriones. Acorde con los desenlaces se utilizaron pruebas no paramétricas para el análisis de las variables cuantitativas y la prueba de χ2 para las variables cualitativas. RESULTADOS: La hiperglucemia moderada pregestacional provocó modificaciones en la ganancia de peso de la madre, la cantidad de reabsorciones, sitios de implantación, pérdidas preimplantación y eficiencia de implantación, así como en la morfología, talla y cantidad de somitas en los embriones. CONCLUSIONES: La diabetes moderada pregestacional alteró el rendimiento reproductivo materno y el crecimiento y desarrollo intrauterino de la descendencia en etapa embrionaria. La embriopatía diabética se manifestó, además, con malformaciones del sistema nervioso central.

Abstract OBJECTIVES: Diabetes mellitus is one of the most frequent disorders of pregnancy with adverse consequences for the mother and a high risk of diabetic embryopathy in the offspring. The objective of the research was to determine the effect of pregestational diabetes with moderate hyperglycemia on maternal reproductive performance, growth, development and embryonic morphology in Wistar rats. MATERIALS AND METHODS: Longitudinal, prospective and experimental study carried out at the Biomedical Research Unit of the University of Medical Sciences of Villa Clara, Cuba. A model of neonatally induced moderate diabetes was used in female Wistar rat pups two days old, by subcutaneous administration of 100 mg/kg of body weight of streptozotocin in a single dose. At 120 days after birth, rats from both experimental groups (diabetic and control) were mated with healthy males. Weight and glycemia were determined during pregnancy and at 11,5 days the cesarean section was performed. The variables of maternal reproductive performance and of growth, development and external morphology in the embryos were analyzed. According to the results, non-parametric tests were used for the analysis of the quantitative variables and the Chi-square test for the qualitative variables. RESULTS: Moderate pregestational diabetes caused changes in maternal weight gain, number of resorptions, implantation sites, preimplantation loss, and implantation efficiency, as well as in morphology, size, and number of somites in embryos. CONCLUSIONS: Moderate pregestational diabetes altered maternal reproductive performance and intrauterine growth and development of embryonic offspring. Diabetic embryopathy was also manifested by malformations of the central nervous system.

Effects of Astragalus membranaceus, Peumus boldus and Curcuma longa extracts in diabetic rats / Efeitos de extratos de Astragalus membranaceus, Peumus boldus e Curcuma longa em ratos com diabetes induzida

Objectives: the aim of this study was to evaluate the effects of the association of dry extracts of Astragalus membranaceus, Peumus boldus and Curcuma longa in rats with induced diabetes. Methods: After the induction of type 2 diabetes by intraperitoneal streptozotocin, male Wistar rats were randomly assigned to groups (n=6) and treated for 20 days. The extracts were suspended in water and administered through orogastric gavage once daily as described: Group I: healthy control (saline); group II: received Astragalus membranaceus, Peumus boldus and Curcuma longa (400 mg/kg/day of each dry extract); group III: received Astragalus membranaceus, Peumus boldus, Curcuma longa (400 mg/kg/day of each dry extract) and glibenclamide (15 mg/kg/day). Fasting glucose, glucose tolerance, alanine aminotransferase, aspartate aminotransferase and fructosamine were evaluated. Results: Fasting blood glucose and glucose tolerance for groups II and III were influenced by treatments (p<0.05). The extracts did not significantly influence the efficacy of glibenclamide. Conclusion: The results found in this study allow us to consider that it is not possible to conclude that the compounds evaluated are not effective in DM in rats, due to variables such as total treatment period, doses, size of pancreatic injury caused by streptozotocin, and diet profile may have influenced the results. The studied compounds have potential for application in diabetes and further studies should be carried out to adjust the treatment.

Objetivos: avaliar os efeitos da associação de extratos secos de Astragalus membranaceus, Peumus boldus e Curcuma longa em ratos com diabetes induzida. Métodos: Após a indução de diabetes tipo 2 (DM) por estreptozotocina intraperitoneal, ratos Wistar machos foram distribuídos aleatoriamente em grupos (n=6) e tratados por 20 dias. Os extratos foram suspensos em água e administrados por gavagem orogástrica uma vez ao dia conforme descrito: Grupo I: controle saudável (solução salina); grupo II: recebeu Astragalus membranaceus, Peumus boldus e Curcuma longa (400 mg/kg/dia de cada extrato seco); grupo III: receberam Astragalus membranaceus, Peumus boldus, Curcuma longa (400 mg/kg/dia de cada extrato seco) e glibenclamida (15 mg/kg/dia). A glicemia de jejum, tolerância à glicose, alanina aminotransferase, aspartato aminotransferase e frutosamina foram avaliados. Resultados: A glicemia de jejum e a tolerância à glicose para os grupos II e III foram influenciadas pelos tratamentos (p<0,05). Os extratos não influenciaram significativamente na eficácia da glibenclamida. Conclusão: Os resultados encontrados neste estudo permitem considerar que não é possível concluir que os compostos avaliados não são eficazes no DM em ratos, devido às variáveis como tempo total de tratamento, doses e tamanho da lesão pancreática causada por estreptozotocina, além do perfil da dieta, que podem ter influenciado os resultados. Os compostos estudados têm potencial para aplicação em diabetes e mais estudos devem ser realizados para adequar o tratamento.

Effect of dual blockade of renin-angiotensin system on renal nephrin and vascular endothelial growth factor – A expression in diabetic-hypertensive rats

Objectives: The effects of early renin-angiotensin system (RAS) blockade using angiotensin-converting enzyme (ACE) inhibitor lisinopril and/or angiotensin receptor blocker valsartan on renal nephrin and vascular endothelial growth factor (VEGF)-A gene expression were investigated in diabetic-hypertensive rats. Materials and Methods: Diabetes and hypertension were induced in adult Wistar rats using streptozotocin (45 mg/kg, i.p.) and N?-nitro-L-arginine methyl ester (60 mg/kg/12 h) for 4 consecutive days. Experimental animals were allocated into six groups (n = 6): normal control, diabetic control, diabetic-hypertensive control and lisinopril-, valsartan- and combination-treated diabetic-hypertensive groups (5 mg/kg/drug/day, p.o., for 21 days). Blood glucose, blood pressure, body weight, kidney weight to body weight ratio, serum albumin, creatinine, total protein and urea were measured and recorded every week. Nephrin and VEGF-A gene expression were measured using real-time polymerase chain reaction. Renal nephrin protein was measured using ELISA as well as nephrin immunostaining. Results: Blood pressure was significantly decreased by all treatments (P ? 0.05). All treatments normalised serum albumin and urea. Serum creatinine significantly decreased, while total protein significantly increased (P ? 0.05). Nephrin gene expression had a non-significant decrease in diabetic-hypertensive rats, yet it was statistically increased with individual treatments (P ? 0.05) and normalised with combined treatment. Renal nephrin protein significantly decreased in diabetic-hypertensive rats, normalised by lisinopril and significantly increased by valsartan and combined treatments (P ? 0.05). VEGF-A expression significantly increased in diabetic-hypertensive rats and significantly decreased with lisinopril and valsartan monotherapy and normalised with combined treatment (P ? 0.05). Immunostaining of nephrin also showed an obvious increase in the case of combined treatment. Conclusion: Early dual blockade of RAS in diabetic-hypertensive rats protected against renal damage and improved renal nephrin and VEGF-A gene expression as well as renal nephrin protein expression.

Protective effect of NeuroEPO on the reproduction of diabetic rats / Efecto protector de la NeuroEPO en la reproducción de ratas diabéticas

Introduction: Pregestational diabetes constitutes a reproductive risk which requires new treatment strategies. NeuroEPO, a variant of the recombinant human erythropoietin produced in Cuba, has neuroprotective and hypoglycemic effects which can be considered for the treatment of this entity. Objective: To evaluate the protective effect of NeuroEPO on the reproduction of diabetic rats. Material and Methods: Four groups of adult female Wistar rats with streptozotocin-induced diabetes were used. During pregnancy, one group received the vehicle and the rest of the groups received different doses of NeuroEPO (0,5 mg/kg, 0,75 mg/kg, and 1 mg/kg) subcutaneously, on alternate days, for a total of six applications. A group of non-diabetic rats was used as a control group. Glycemia and reproductive variables were evaluated. For comparisons, Analysis of Variance and Fisher's Exact Test were used. There were significant differences with p-values less than 0,05. Results: The group with vehicle presented maintained hyperglycemia, fewer implantations, and embryos, and increased gestational losses. In the group receiving 0,5 mg/kg of NeuroEPO, glycemia decreased significantly and the results of the reproductive variables were similar to the group of non-diabetic rats. With higher doses of NeuroEPO, gestational losses were increased. No congenital malformations were identified in either group. Conclusions: The repeated administration of 0,5 mg/kg of NeuroEPO has a beneficial effect on the reproduction of diabetic rats, which may be associated with the reduction of hyperglycemia. Other cytoprotective mechanisms of NeuroEPO should be evaluated in future studies(AU)

Introducción: la diabetes pre-gestacional constituye un riesgo reproductivo, lo que requiere nuevas estrategias de tratamiento. Teniendo en cuenta que la NeuroEPO, una variante de la eritropoyetina recombinante humana producida en Cuba, tiene efectos neuroprotectores e hipoglicemiantes. Objetivo: evaluar el efecto protector de la NeuroEPO en la reproducción de ratas diabéticas. Material y Métodos: se utilizaron cuatro grupos de ratas Wistar hembras adultas, con diabetes inducida por estreptozotocina. Durante la gestación, un grupo recibió el vehículo y el resto diferentes dosis de NeuroEPO (0,5 mg/kg, 0,75 mg/kg y 1 mg/kg), por vía subcutánea, en días alternos, para un total de seis aplicaciones. Se empleó un grupo de ratas no-diabéticas como control. Se evaluó la glicemia y variables reproductivas. Para las comparaciones se empleó el Análisis de Varianza y la Prueba Exacta de Fisher. Las diferencias se consideraron significativas con valores de p menores que 0,05. Resultados: el grupo con vehículo presentó hiperglicemia mantenida, menor número de implantaciones y embriones, e incremento de las pérdidas gestacionales. En el grupo que recibió 0,5 mg/kg de NeuroEPO, la glicemia disminuyó de forma significativa y los resultados de las variables reproductivas fueron similares al grupo de ratas no-diabéticas. Con las dosis superiores de NeuroEPO se incrementaron las pérdidas gestacionales. No se identificaron malformaciones congénitas en ninguno de los grupos. Conclusiones: la administración reiterada de 0,5 mg/kg de NeuroEPO tiene efecto beneficioso en la reproducción de ratas diabéticas, que puede estar asociado a la reducción de la hiperglicemia. Otros mecanismos citoprotectores de la NeuroEPO deben ser evaluados en futuros estudios(AU)

Interaction of Carthamus oil, chromium picolinate and glyburide in blood glucose and its impact on liver enzymes and lipid profile in diabetes-induced rats

SUMMARY Introduction: Carthamus oil is a compound that has the potential to be used in numerous applications due to its anti-inflammatory, antioxidant, immunomodulatory and neuroprotective effects. Chromium picolinate has been indicated for the control of insulin resistance. Aim: To evaluate the effect of Carthamus oil (30 mg/kg) and chromium picolinate (5 µg/kg) interaction with oral glyburide in chemically diabetes-induced Wistar rats and its influence on drug therapy. Method: Diabetes mellitus was induced with streptozotocin, and the animals were randomized into experimental groups (n= 6/group), who received gastric gavage treatments for ten days, G1: control, G2: diabetic and received glyburide, G3: diabetic and received the interaction of Carthamus oil and chromium picolinate, G4: diabetic and received the interaction ofglyburide, Carthamus oil and chromium picolinate. After the treatment period, fasting blood glucose, post-sucrose blood glucose, total cholesterol and triglyceride levels, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in blood serum were compared, in addition to urine analysis. Results: In this study, the only altered parameters were the post-sucrose blood glucose measurement with the lowest result for G4 (P <0.05) and the ALT measurement, with lower values for G4 (P <0.05) compared to G1. Conclusion: It can be concluded that the unprecedented interaction of Carthamus oil, chromium picolinate and glyburide contributed to the reduction of blood glucose and serum levels of ALT in diabetic rats and is promising for future studies in humans.

Introdução: o óleo de cártamo (Carthamus oil) tem sido utilizado em diversas aplicações devido suas ações antiinflamatória, antioxidante, imunomoduladora e neuro protetora. O picolinato de cromo tem sido indicado para o controle da resistência à insulina. Objetivo: avaliar o efeito da interação de óleo de cártamo (30 mg/kg) e picolinato de cromo (5 µg/kg) com glibenclamida em ratos com diabetes induzida. Metodologia: a indução de diabetes mellitus foi realizada com injeção intra-peritoneal de estreptozotocina e os animais foram aleatoriamente distribuidos em grupos experimentais (n= 6/grupo), que receberam os tratamentos por gavagem gástrica durante dez dias, G1: controle, G2: grupo diabético que recebeu gliben-clamida, G3: grupo diabético que recebeu óleo de cártamo e picolinato de cromo, G4: grupo diabético que recebeu glibenclamida, óleo de cártamo e picolinato de cromo. Após os dias de tratamento via oral, determinou-se o peso corpóreo, glicemia de jejum, colesterol total, triglicerideos, glicemia após uma hora de gavagem gástrica com sacarose, transaminases hepáticas e a avaliação da urina. Resultados: a análise estatistica dos dados indicou que os únicos parâmetros alterados foram a glicemia após a ingestão de sacarose, os menores valores obtidos foram em G4 (P <0.05) e a redução dos niveis séricos de ALT em G4 (P <0.05) quando comparados com G1. Conclusão: a interação inédita do óleo de cártamo, picolinato de cromo e glibencla-mida contribuiu para a redução da glicose sanguinea e dos niveis séricos de ALT em ratos diabéticos, é promissora para estudos futuros em humanos.

Introducción: el aceite de cártamo (Carthamus oil) se ha utilizado en diversas aplicaciones debido a sus propiedades antiinflamatorias, antioxidantes, inmunomodu-ladoras y neuroprotectoras. El picolinato de cromo ha sido indicado para el control de la resistencia a la insulina. Objetivo: evaluar el efecto de la interacción de aceite de cártamo (30 mg/kg) y picolinato de cromo (5 µg/kg) con glibenclamida en ratas con diabetes inducida. Metodología: la inducción de diabetes mellitus se realizó con inyección intraperitoneal de estreptozotocina y los animales se distribuyeron aleatoriamente en grupos experimentales (n= 6/grupo), los cuales recibieron tratamientos por sonda gástrica durante diez dias, G1: control, G2: grupo diabético que recibieron glibenclamida, G3: grupo diabético que recibió aceite de cártamo y picolinato de cromo, G4: grupo diabético que recibió glibenclamida, aceite de cártamo y picolinato de cromo. Después de los dias de tratamiento oral, se determinó peso corporal, glucosa en ayunas, colesterol total, triglicéridos, glucosa después de una hora de sonda gástrica con sacarosa, transaminasas hepáticas y evaluación de orina. Resultados: el análisis estadistico de los datos indicó que los únicos parámetros alterados fueron la glucosa en sangre después de la ingesta de sacarosa, los valores más bajos obtenidos fueron en G4 (P <0,05) y la reducción de los niveles séricos de ALT en G4 (P <0,05) cuando en comparación con G1. Conclusión: la interacción sin precedentes del aceite de cártamo, el picolinato de cromo y la glibenclamida contribuyó a la reducción de los niveles de glucosa en sangre y ALT sérica en ratas diabéticas, es prometedora para futuros estudios en humanos.

Efecto hipoglicemiante de la NeuroEPO en ratas con y sin diabetes mellitus / Hypoglycemic effect of NeuroEPO in diabetic and non-diabetic rats

RESUMEN Introducción: La NeuroEPO es una variante no-hematopoyética de la eritropoyetina recombinante humana, que pudiera tener efecto hipoglicemiante. Objetivo: Evaluar la influencia de la NeuroEPO sobre la glicemia de ratas con diabetes mellitus y ratas no-diabéticas. Material y Métodos: Se realizaron experimentos en ratas Wistar con diabetes inducida por estreptozotocina, con y sin tratamiento con insulina, y en ratas no-diabéticas con una sobrecarga de glucosa. En cada experimento, un grupo recibió una inyección subcutánea de NeuroEPO (0,5 mg/kg) y otro el vehículo, y se determinó la glicemia durante 120 minutos. Se realizaron comparaciones mediante análisis de varianza de una y dos vías, seguidas por la prueba de Bonferroni. Las diferencias se consideraron significativas con valores de p < 0,05. Resultados: En las ratas diabéticas sin tratamiento con insulina, los niveles de glicemia del grupo con NeuroEPO disminuyeron de forma significativa. En las ratas no-diabéticas que recibieron NeuroEPO y una sobrecarga de glucosa, la glicemia fue similar al grupo control. En las ratas diabéticas que recibieron NeuroEPO e insulina la reducción de la glicemia fue mayor que en el grupo que solo recibió insulina. Conclusiones: La NeuroEPO tiene un efecto hipoglicemiante en ratas diabéticas, por un mecanismo insulinotrópico que muestra sinergismo con la insulina en el tratamiento de la hiperglicemia. Sin embargo, la NeuroEPO no influye en la tolerancia a la glucosa de ratas no-diabéticas, al menos de forma inmediata. Es necesario profundizar en los mecanismos mediante los cuales la NeuroEPO puede reducir la hiperglicemia, y la influencia de esta sustancia en condiciones de normoglicemia.

ABSTRACT Introduction: NeuroEPO is a non-hematopoietic variant of human recombinant erythropoietin, which may have a hypoglycemic effect. Objectives: To evaluate the influence of NeuroEPO on glycemia in diabetic and non-diabetic rats. Material and Methods: The experiments were conducted in Wistar rats with streptozotocin-induced diabetes with and without insulin treatment, and in non-diabetic rats with glucose overload. In each experiment, one group received a subcutaneous injection of NeuroEPO (0.5 mg/kg) and the other group received a vehicle. Glycemia was determined in 120 min. Comparisons were made using one-and two-way analysis of variance, followed by the Bonferroni test. The differences were considered significant with p values < 0,05. Results: In diabetic rats without insulin treatment, glycemic levels decreased significantly in the group that received NeuroEPO. In nondiabetic rats that received NeuroEPO and a glucose overload, glycemia was similar to that in the control group. In diabetic rats that received NeuroEPO and insulin, the glycemia reduction was greater than in the group that only received insulin. Conclusions: NeuroEPO has a hypoglycemic effect in diabetic rats due to an insulinotropic mechanism that shows synergism with insulin in the treatment of hyperglycemia. However, NeuroEPO does not influence the glucose tolerance in non-diabetic rats, at least immediately. It is necessary to delve into the mechanisms by which NeuroEPO can reduce hyperglycemia and the influence of this substance under conditions of normoglycemia.

Anti-hyperglycemic and anti-hypercholesterolemic activity of Schouwia schimperi in glucose loaded and streptozotocin induced diabetic rats

Background: Diabetes mellitus has assumed epidemic proportion, its incidence is continuously increasing although of that estimates are imprecise, only providing a rough picture, and probably underestimate the disease burden. There were about 150 million cases estimated in the year 2000 which rose to 422 million people worldwide in 2020 according to the World Health Organization statistics. Medicinal plants such as Schouwia schimperi are one of many traditional treatments used in folk medicine by the people of Eastern Sudan for diabetes mellitus but have not been studied or evaluated scientifically. Aims and Objectives: This study evaluates the hypoglycemic and hypolipidemic effect of S. schimperi ethanol extract and compares it with standard glibenclamide in glucose loaded rats and streptozotocin induced diabetic rats. Materials and Methods: Diabetes mellitus was experimentally induced in rats by subcutaneous injection of streptozotocin at a dose of 60 mg/kg. S. schimperi ethanol extract was given orally at doses of 200 and 400 mg/kg and compared with control (2 ml distilled water) and standard (Glibenclamide 10 mg/kg). The same doses were given to glucose loaded diabetic rats as a model for type 2 diabetes mellitus. Results: The 200 mg/kg dose significantly lowered the plasma glucose levels in glucose loaded rats by 31% 2 h after the glucose load (P < 0.05) and by 68% in comparison to the negative control, the 400 mg/kg dose reduced plasma glucose levels by 33% in comparison to negative control (P < 0.05). Reductions in plasma glucose levels were 33.12% and 12.34% after 4 h of the glucose load for the 200 mg/kg and the 400 mg/kg doses respectively. In streptozotocin diabetic rats no significant reductions in plasma glucose levels were seen. However, strong hypocholesterolemic effect was seen after 3 h for both of the 200 mg/kg and 400 mg/kg doses by 85.4% (P < 0.05) and 88.2% (P < 0.05), respectively, and by 89.97% (P < 0.001) and 90.6% (P < 0.001) respectively 6 h after oral administration. Conclusion: Our study concludes that S. schimperi extract has a favorable effect in reducing plasma glucose in glucose loaded rats and excellent hypolipidemic effects.

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.

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)

Investigation of the protective and therapeutic effects of ß-aminoisobutyric acid (BAIBA) and Thymoquinone in the diabetic nephropathy / Investigación de los efectos protectores y terapéuticos del ácido ß-aminoisobutírico (BAIBA) y la timoquinona en la nefropatía diabética

In this study, against streptozotocin (STZ) induced diapetic nephropathy (DN); it is aimed to investigate the use of thymoquinone (TQ) and ß-aminoisobutyric acid (BAIBA) and to compare the effects of these agents. With random selection of 35 male rats, five groups (seven rats in each group) were constituted as follows: Control, STZ, STZ + TQ, STZ + BAIBA, STZ + TQ + BAIBA. In the STZ group; body weight, glutathione (GSH) and insulin levels decreased, relative kidney weight, malondialdehyde (MDA), glucose, blood urea nitrogen (BUN) and creatinine (Cr) levels were increased. Also, in kidney tissue; histopathological changes (such as thickening of the capsular, glomerular and tubular basement membranes, increased mesangial matrix amount, increased cytoplasmic vacuolization in some of the tubular epithelial cells, increased tumor necrosis factor-alpha (TNF-α) expression, and inflammatory cell infiltrations in interstitial tissue) were detected. It was observed that these changes occurring after diabetes mellitus (DM) reversed significantly in TQ, BAIBA and TQ + BAIBA groups.

En este estudio, contra la nefropatía diapética (ND) inducida por estreptozotocina (STZ); tiene como objetivo investigar el uso de timoquinona (TQ) y ácido ß-aminoisobutírico (BAIBA) y comparar los efectos de estos agentes. Con la selección aleatoria de 35 ratas macho, se constituyeron cinco grupos (siete ratas en cada grupo) como sigue: Control, STZ, STZ + TQ, STZ + BAIBA, STZ + TQ + BAIBA. En el grupo STZ; el peso corporal, los niveles de glutatión (GSH) y de insulina disminuyeron, el peso relativo de los riñones, el malondialdehído (MDA), la glucosa, el nitrógeno ureico en sangre (BUN) y los niveles de creatinina (Cr) aumentaron. Además, en tejido renal; se detectaron cambios histopatológicos (como engrosamiento de las membranas basales capsular, glomerular y tubular, aumento de la cantidad de matriz mesangial, aumento de la vacuolización citoplasmática en algunas de las células epiteliales tubulares, aumento de la expresión del factor de necrosis tumoral alfa (TNF-α) e infiltraciones de células inflamatorias en tejido intersticial). Se observó que estos cambios que ocurren después de la diabetes mellitus (DM) se revirtieron significativamente en los grupos TQ, BAIBA y TQ + BAIBA.

Small bronchiolar histopathological changes related to prolonged diabetes / Pequeños cambios histopatológicos bronquiolares relacionados con la diabetes prolongada

SUMMARY: Diabetes mellitus increases the risk of developing chronic obstructive pulmonary disease (COPD). The small bronchiole is a prominent site of airflow obstruction that causes increased airway resistance in patients with the COPD. Therefore, the histological and ultrastructural changes in small bronchioles in streptozotocin (STZ)-induced chronic diabetes were determined. Twenty-four weeks after STZ induction, rats were sacrificed, and the right and left lungs were collected for examination by light and electron microscopy. The alterations to the small bronchioles were the same in both lungs of these diabetic rats. The bronchiolar epithelial cells, both ciliated and secretory club cells, showed pyknotic nuclei and damaged cytoplasmic organelles. Increased thickening of the bronchiolar wall occurred in diabetic rats due to smooth muscle layer thickening, inflammatory cell infiltration, and increased numbers of myofibroblasts with collagen deposition.These results indicated that chronic diabetes caused extreme damage to small bronchioles, which may lead to chronic small airway obstruction and ultimately increase the likelihood of COPD progression. This basic knowledge provides a better understanding of the progression of pathogenesis in the small airways of patients with prolonged diabetes.

RESUMEN: La diabetes mellitus aumenta el riesgo de desarrollar enfermedad pulmonar obstructiva crónica (EPOC). El bronquiolo es un sitio prominente de obstrucción del flujo de aire que causa una mayor resistencia de las vías respiratorias en pacientes con EPOC. Por lo tanto, se determinaron los cambios histológicos y ultraestructurales en los bronquiolos en la diabetes crónica inducida por estreptozotocina (STZ). 24 semanas después de la inducción de STZ, se sacrificaron las ratas y se analizaron los pulmones derecho e izquierdo por microscopía óptica y electrónica. Las alteraciones de los pequeños bronquiolos fueron las mismas en ambos pulmones de estas ratas diabéticas. Las células epiteliales bronquiolares, tanto ciliadas como secretoras, mostraban núcleos picnóticos y orgánelos citoplasmáticos dañados. Se produjo un aumento del engrosamiento de la pared bronquiolar en ratas diabéticas debido al engrosamiento de la capa de músculo liso, infiltración de células inflamatorias y un mayor número de miofibroblastos con colágeno. Estos resultados indicaron que la diabetes crónica causaba daño extremo a los pequeños bronquiolos, lo que puede conducir a una obstrucción crónica de las vías respiratorias pequeñas y además aumentar la probabilidad de progresión de la EPOC. Esta información proporcionará un mejor conocimiento de la patogénesis en las vías respiratorias pequeñas de los pacientes con diabetes prolongada.

The Effects on Offspring of Diabetes Mellitus Induced by Chemical Agents in Rats with Advanced Pregnancy

ABSTRACT Background: Gestational diabetes mellitus is an increasingly frequent metabolic disorder that is important for both baby and mother. New studies on the development and treatment of the disease are required. Objective: To investigate the effects on offspring's survival and the biochemical values of diabetes mellitus, induced by different doses of two chemical agents among 35 rats with advanced pregnancy. Methods: The rats were randomly divided into five groups, with the rats in Group 1 as the control group. Alloxan was administered intraperitoneally at doses of 40 and 60 mg/kg in Groups 2 and 3, respectively. Streptozotocin was injected intraperitoneally at doses of 40 and 60 mg/kg in Groups 4 and 5, respectively. Deliveries were monitored, and offspring numbers, survival rates and congenital anomalies were recorded. At the end of the study, blood was drawn from one female offspring in each group; glucose, total protein, albumin, triglyceride, cholesterol, calcium and phosphorus levels were measured, and inter-group comparisons were made. Diabetic agents administered at various doses prolonged the duration of pregnancy. Results: Offspring's deaths were most frequent in the alloxan groups. The number of offspring mortalities in the streptozotocin group was higher than that of the control group, but lower than that of the alloxan group. No differences in glucose, total protein, albumin, triglyceride, cholesterol, calcium and phosphorus levels were observed between the groups. These results indicate that the female offspring, born from rats with gestational diabetes mellitus induced by different chemicals, were only clinically affected. No effect of the type of chemicals on the results was found. Conclusion: The use of streptozotocin in the studies on female offspring born from rats with gestational diabetes mellitus is recommended.