Effects of gut microbiota on five absorbed components of Berberis kansuensis in rat serum by HPLC-QqQ-MS / 中国中药杂志

To elucidate the absorption and metabolism of alkaloids in Berberis kansuensis in vivo, a high performance liquid chromatography-triple quadrupole mass spectrometry(HPLC-QqQ-MS) method was developed to qualitatively and quantitatively analyze the absorption components in rat serum in multiple-reaction monitoring mode. The mobile phase consisted of 0.1% formic acid and acetonitrile with a gradient elution mode. In addition, to investigate the effects of gut microbiota on five absorbed components of B. kansuensis in rat serum, diabetic rat and pseudo germ-free diabetic rat models were established, and partial least squares discriminant analysis and One-way ANOVA were used to study the content differences of five components among different groups. In this study, a HPLC-QqQ-MS method for quantitative analysis of five components in rat serum after oral administration of B. kansuensis was established for the first time. It was found that there were differences in the five constituents in rat serum between different groups. By comparing the normal group with the diabetic model group, we found that the absorption and metabolism capacities of berberine and magnoflorine were different under the health and pathological conditions. It was also found that the serum levels of berberine, magnoflorine and jatrorrhizine in pseudo germ-free diabetic rats were significantly lower than those in diabetic rats, indicating that gut microbiota plays an important role in the metabolism of alkaloids of B. kansuensis in vivo. These results provide a good reference for clarifying the active ingredients of B. kansuensis in the treatment of diabetes.

Macrophage migration inhibitory factor antagonist (p425) ameliorates kidney histopathological and functional changes in diabetic rats / Antagonista (p425) do fator de inibição da migração de macrófagos (MIF) melhora as alterações histopatológicas e funcionais renais em ratos diabéticos

Abstract Introduction: It is hypothesized that increased macrophage migration inhibitory factor (MIF) expression may contribute to diabetic nephropathy (DN) pathogenesis. The aim of the present study was to investigate the renal effects of MIF inhibition in a diabetic experimental model. Methods: Eighteen male Wistar rats (230 ± 20 g) were divided into three groups: 1) control, 2) diabetic (STZ, 50 mg/kg, dissolved in saline, ip), 3) diabetic + MIF antagonist (p425, 1 mg/kg per day, ip, on the 21th day, for 21 consecutive days). The treatment started since we founwd a significant increase in urine albumin excretion (UAE) rate in the diabetic rats in comparison with the control rats. The rats were kept individually in metabolic cages (8 AM-2 PM) and urine samples were collected in the 21 and 42th day. At the end, blood and tissue samples were collected for biochemical (BS, UPE, urine GAG, BUN, Cr, Na, and K) and histological analyses. Results: The results of this study showed that MIF antagonist (p425) significantly decreased urine protein and GAG excretion, urine protein/creatinine ratio, and serum BUN and Cr in the streptozotocin-induced DN in the rats. Pathological changes were significantly alleviated in the MIF antagonist (p425)-administered DN rats. Conclusion: Collectively, these data suggested that MIF antagonist (p425) was able to protect against functional and histopathological injury in the DN.

Resumo Introdução: Supõe-se que elevações da expressão do fator de inibição da migração de macrófagos (MIF) possam contribuir para a patogênese da nefropatia diabética (ND). O objetivo do presente estudo foi investigar os efeitos renais da inibição do MIF em um modelo experimental diabético. Métodos: Dezoito ratos Wistar machos (230 ± 20g) foram divididos em três grupos: 1) controle, 2) diabético (STZ 50 mg/kg dissolvida em soro fisiológico, IP), 3) diabético + antagonista do MIF (p425 1 mg/kg por dia IP no 21o dia por 21 dias consecutivos). O tratamento começou após a identificação de aumento significativo na albuminúria nos ratos diabéticos em relação aos controles. Os ratos foram mantidos individualmente em gaiolas metabólicas (8h-14h) e amostras de urina foram colhidas no 21o e no 42o dia. Ao final do estudo, amostras de sangue e tecido foram colhidas para análises bioquímicas (BS, excreção urinária de proteína, excreção urinária de GAGs, BUN, Cr, Na e K) e histológicas. Resultados: O presente estudo demonstrou que o antagonista do MIF (p425) diminuiu significativamente proteinúria, excreção urinária de GAGs , relação proteína/creatinina na urina, BUN e Cr no grupo com ND induzida por estreptozotocina. As alterações patológicas foram significativamente abrandadas nos ratos com ND que receberam antagonista do MIF (p425). Conclusão: Coletivamente, os dados sugerem que o antagonista do MIF (p425) teve efeito protetor contra lesões funcionais e histopatológicas da ND.

Diabetic Rats Present High Mean Platelet Count in the Presence of Oral Infections

Abstract Platelet count is associated with inflammatory diseases like diabetes mellitus (DM), which in turn, is related in a bidirectional manner with apical periodontitis and periodontal disease. The aim of this study was to evaluate the effects of apical periodontitis and/or periodontal disease on mean platelet count in a rat model of diabetes mellitus. Eighty Wistar rats were randomly divided into 8 groups (n=10): control (C), apical periodontitis (AP), periodontal disease (PD), apical periodontitis with periodontal disease (AP-PD), diabetes mellitus (DM), diabetes mellitus with apical periodontitis (DM-AP), diabetes mellitus with periodontal disease (DM-PD) and diabetes mellitus with apical periodontitis and periodontal disease (DM-AP-PD). Rats were anesthetized and DM was induced with a single dose of streptozotocin diluted in citrate buffer solution. After 6 days, the DM was confirmed. The animals were sedated and apical periodontitis was induced by dental exposure and periodontal disease was induced by periodontal ligature. After 30 days, animals were anesthetized and the blood was collected by cardiac puncture. Samples were processed and the mean platelet count was obtained. Data were tabulated and subjected to statistical analysis (p<0.05). Diabetic rats had higher mean glycemic levels compared with nondiabetic rats at 6 and 36 days after DM induction (p<0.05). The DM-PD and DM-PD-AP groups showed increased mean platelet count compared to control and AP groups (p<0.05). The periodontal disease alone or associated with apical periodontitis influence mean platelet count in a rat model of diabetes mellitus.

Resumo A contagem de plaquetas está associada a doenças inflamatórias como a diabetes mellitus (DM), que, por sua vez, está relacionada de forma bidirecional com periodontite apical e com a doença periodontal. O objetivo deste estudo foi avaliar os efeitos da periodontite apical e/ou da doença periodontal na contagem de plaquetas utilizando o modelo de rato para DM. Oitenta ratos Wistar foram divididos aleatoriamente em 8 grupos (n=10): controle (C), periodontite apical (AP), doença periodontal (PD), periodontite apical com doença periodontal (AP-PD), diabetes mellitus (DM), diabetes mellitus com periodontite apical (DM-AP), diabetes mellitus com doença periodontal (DM-PD) e diabetes mellitus com periodontite apical e doença periodontal (DM-AP-PD). Os ratos foram anestesiados e a DM foi induzida com uma dose única de estreptozotocina diluída na solução tampão citrato. Após 6 dias, o DM foi confirmada. Os animais foram sedados e a periodontite apical foi induzida pela exposição dentária e a doença periodontal foi induzida por ligadura periodontal. Após 30 dias, os animais foram anestesiados e o sangue foi coletado por punção cardíaca. As amostras foram processadas e a contagem média de plaquetas foi obtida. Os dados foram tabulados e submetidos a análise estatística (p <0,05). Os ratos diabéticos apresentaram níveis glicêmicos médios mais elevados em comparação com ratos não diabéticos aos 6 e 36 dias após a indução da DM (p <0,05). Os grupos DM-PD e DM-PD-AP mostraram aumento da contagem média de plaquetas em comparação com os grupos controle e AP (p <0,05). A doença periodontal isolada ou associada à periodontite apical influencia na contagem de plaquetas em modelo de rato para diabetes mellitus.

Influence of the use of testosterone associated with physical training on some hematologic and physical parameters in older rats with alloxan-induced diabetes

ABSTRACT Objective This study investigated the possible blood changes in wistar rats elderly with and without treatment with anabolic steroids submitted physical training. Materials and methods Elderly rats (32) were divided into four groups: normal (N), treated normal (NT), diabetic (D) and treated diabetic (DT). They were submitted to 20 sessions of swimming with overload (5% body weight), 40 min/day for four weeks. The NT and DT groups received application of testosterone twice a week. At the end of the sessions, the animals were subjected to swimming until exhaustion and then killed for removal of blood and visceral fat. We evaluated maximum swim time, weight of visceral fat, erythrogram, leukogram, lipidogram and serum levels of glucose, lactate, aspartate aminotransferase and creatine kinase. The results were compared using one-way ANOVA followed by the post hoc Tukey test. Results In elderly diabetic rats, the use of anabolic associated with physical training in older rats resulted in improvement in erythrogram, lipidogram and physical performance for high-intensity aerobic exercise. However, it was related to changes in leukocyte count, probably associated with inflammation. Conclusion The combination of the use of testosterone with physical training, followed by maximal effort test caused changes hematological and biochemical can be associated with improvement in physiological characteristics, with increase of the swimming time and decrease of visceral fat levels, improvement in aerobic metabolism of fatty acids and glucose in normal and diabetic animals.

Trichuris trichiura in a post-Colonial Brazilian mummy

Trichuris trichiura is a soil-transmitted helminth which is prevalent in warm, moist, tropical and subtropical regions of the world with poor sanitation. Heavy whipworm can result either in Trichuris dysenteric syndrome - especially in children - or in a chronic colitis. In heavy infections, worms can spread proximally and may cause ileitis. Here we provide first microscopic evidence for a T. trichiura adult worm embedded in the rectum of a post-Colonial Brazilian adult mummy. During Colonial and post-Colonial times, many European chroniclers described a parasitic disease named Maculo whose symptomatology coincides with heavy helminthiasis. Based on our findings and on comparison of ancient textual evidence with modern description of heavy whipworm, we feel confident in considering that the two syndromes are expressions of the same pathological condition.

Evaluation of Antidiabetic and the Effect of Methanolic Leaf Extract of Jatropha curcas on Some Biochemical Parameters in Alloxan-induced Diabetic Male Albino Rats.

Aims: The study evaluates the antidiabetic, and the effect of methanolic leaf extract of Jatropha curcas on some biochemical parameters in alloxan-induced diabetic male albino rats (Wistar strain). Place and Duration of Study: The study was carried out for ten months in 2012 in Biochemistry Laboratory, Department of Science Laboratory Technology (Biochemistry Unit), School of Technology, Lagos State Polytechnic, Ikorodu, Lagos- Nigeria, and Department of Hematology and blood transfusion, APIN Clinic LUTH, University of Lagos, Nigeria. Methodology: Qualitative phytochemical analysis of the extract were carried out to determine the presence of secondary metabolites present in the extract of Jatropha curcas. The animals were weighed using weighing balance, there blood sugar levels were assayed using Accu-chek Active Glucometer and blood glucose test strips. The hematological parameters were determined using BC-3200 Auto Hematology Analyzer, lipid profiles, total protein, total bilirubin and liver biomarker enzymes were assayed using Randox kits. Results: The phytochemical constituents of J. curcas extract indicate the presence of secondary metabolites like tannins, saponins, flavonoids etc. The weight of diabetic untreated rats were significantly (P<0.05) reduced when compared to other groups. The animals treated with glibenclamide, 150 and 250mg/Kg body weight of J. curcas extract showed significant decrease (P<0.05) of blood sugar level compared to the untreated rats. The extract does possess hematopoietic activity and is not hematotoxic. J. curcas had hypolipidemic effect and can be used in the management of diabetes. The extract significantly reduced (P<0.05) total bilirubin and liver biomarker enzymes (AST, ALT and ALP). Conclusion: The results show that the methanolic leaf extract of Jatropha curcas can be used in the management of diabetes.

Insulin secreting and α-glucosidase inhibitory activity of hexane extract of Annona squamosa Linn. in streptozotocin (STZ) induced diabetic rats.

The hexane extract of A. squamosa (ASHE) in 100 and 400 mg/kg body weight dose raised the insulin level when compared with Glimepiride (1 mg/kg) and also inhibited α-glucosidase activity when compared with Acarbose (10 mg/kg) in streptozotocin induced diabetic rats. The ASHE significantly reduced peak blood glucose (Gp30) and area under curve (AUC) in diabetic rats in oral glucose (OGTT) and oral sucrose (OSTT) tolerance test, but there was more reduction of Gp30 value than AUC in OSTT. Thus, it can be suggested that the ASHE, has hypoglycemic role at 2 levels, i.e. it acts as secretagogue and also inhibits the intestinal enzymes, responsible for glucose metabolism.

Efecto de los extractos de Geranium ayavacense W. (Pasuchaca) sobre la glicemia en ratas con diabetes mellitus experimental / Effect of extracts of Geranium ayavacense W. (Pasuchaca) on glycemia on rats with experimental diabetes mellitus

Objetivos . Determinar si el extracto acuoso liofilizado de Geranium ayavacense (Pasuchaca) tiene algún efecto sobre la glicemia en ratas con diabetes mellitus experimental. Materiales y métodos. La diabetes experimental fue inducida con aloxano. Las ratas cumplieron los criterios: glicemia > 200 mg/dL posadministración de aloxano y un peso > 200 g. Las ratas con diabetes experimental fueron distribuidas en seis grupos de ocho ratas cada uno. El grupo I recibió 3 mL de agua destilada (control); el grupo II recibió Geranium ayavacense 12,7 mg/kg; el grupo III recibió Geranium ayavacense 100 mg/kg; el grupo IV recibió Geranium ayavacense 200 mg/kg; el grupo V recibió Geranium ayavacense 300 mg/kg; el grupo VI recibió Geranium ayavacense 500 mg/kg. Se determinó la glicemia basal. Las evaluaciones de la glicemia se realizaron a la 1.ª, 3.ª, 6.ª, 12.ª y 24ª hora después de administrar las diferentes intervenciones. Resultados. Los grupos de Geranium ayavacense de 300 y 500 mg/kg disminuyeron significativamente (p<0,01) la glicemia en todas las horas evaluadas después de la administración de los extractos, cuando se compara con el grupo control. El grupo de Geranium ayavacense de 300 mg/kg decreció su glucosa sanguínea en 8,14; 10,68; 14,87; 19.36 y 23,7% a la 1.ª, 3.ª, 6.ª, 12.ª y 24.ª hora respectivamente. Conclusiones. En condiciones experimentales, el extracto acuoso de Geranium ayavacense tiene efecto hipoglicemiante en ratas.

Objectives . To determine if the lyophilized aqueous extract of Geranium ayavacense (Pasuchaca) has any effect on glycemia in rats with experimental diabetes mellitus. Materials and methods. Experimental diabetes was induced with alloxan. Rats included in the study met the following criteria: glycemia greater than 200 mg/dL post administration of alloxan, and with a weight greater than 200 g. Rats with experimental diabetes were divided into six groups of eight rats each. Group I received 3 mL of distilled water (control); group II received Geranium ayavacense 12.7 mg/kg; group III received Geranium ayavacense 100 mg/kg; group IV received Geranium ayavacense 200 mg/kg; group V received Geranium ayavacense 300 mg/kg; group VI received Geranium ayavacense 500 mg/kg. Basal glycemia was determined. Glycemia evaluations were performed at the 1st, 3rd, 6th, 12th and 24th hour after administrating the different interventions. Results. Geranium ayavacense groups of 300 and 500 mg/kg decreased glycemia significantly (p <0.01) in every hour assessed after administration of the extract, when compared with the control group. Geranium ayavacense group of 300 mg/kg decreased their blood glucose 8.14; 10.68; 14.87; 19.36 and 23.7% in the 1st, 3rd, 6th, 12th and 24th hour respectively. Conclusions. Under experimental conditions, the aqueous extract of Geranium ayavacense has hypoglycemic effects in rats.

Diet control to achieve euglycemia induces significant loss of heart and liver weight via increased autophagy compared with ad libitum diet in diabetic rats

Intensive glucose control increases the all-cause mortality in type 2 diabetes mellitus (T2DM); however, the underlying mechanisms remain unclear. We hypothesized that strict diet control to achieve euglycemia in diabetes damages major organs, increasing the mortality risk. To evaluate effects on major organs when euglycemia is obtained by diet control, we generated a model of end-stage T2DM in 13-week-old Sprague-Dawley rats by subtotal pancreatectomy, followed by ad libitum feeding for 5 weeks. We divided these rats into two groups and for the subsequent 6 weeks provided ad libitum feeding to half (AL, n=12) and a calorie-controlled diet to the other half (R, n=12). To avoid hypoglycemia, the degree of calorie restriction in the R group was isocaloric (g per kg body weight per day) compared with a sham-operated control group (C, n=12). During the 6-week diet control period, AL rats ate three times more than rats in the C or R groups, developing hyperglycemia with renal hyperplasia. R group achieved euglycemia but lost overall body weight significantly compared with the C or AL group (49 or 22%, respectively), heart weight (39 or 23%, respectively) and liver weight (50 or 46%, respectively). Autophagy levels in the heart and liver were the highest in the R group (P<0.01), which also had the lowest pAkt/Akt levels among the groups (P<0.05 in the heart; P<0.01 in the liver). In conclusion, glycemic control achieved by diet control can prevent hyperglycemia-induced renal hyperplasia in diabetes but may be deleterious even at isocaloric rate when insulin is deficient because of significant loss of heart and liver mass via increased autophagy.

Evaluation of the hypoglycaemic activity of Petiveria alliacea (Guinea Hen Weed) extracts in normoglycaemic and diabetic rat models / Evaluación de la actividad hipoglicémica de los extractos de Petiveria alliacea (Yerba de Guinea o Anamú) en modelos de ratas diabéticas y normoglicémicase

OBJECTIVE: Petiveria alliacea (p alliacea) has ethno-traditional use as a hypoglycaemic agent in Jamaica and is yet to be scientifically validated as such. Therefore, extracts of aerial parts of the plant were evaluated for hypoglycaemic activity in normoglycaemic and diabetic rats. METHODS: Aqueous and hexane extracts prepared from leaves of p alliacea were tested for hypoglycaemic activity. An acute administration of the extracts (200 and 400 mg/kg body weight) was evaluated in normoglycaemic rats. Additionally, the hypoglycaemic effect ofsub-chronic administration was assessed in streptozotocin-induced diabetic rats. Blood glucose was recorded using a glucometer and test strips. Data were analysed using Student's t-test (p < 0.05). RESULTS: The aqueous and hexane extracts demonstrated no significant reduction of fasting blood glucose (FBG) and no significant improvement of glucose tolerance in normal rats. The aqueous extract (400 mg/kg body weight) increased FBG from 4.75 ± 0.28 mmol/L to 5.88 ± 0.46 when compared to control (p < 0.001). In diabetic rats, the hexane extract (400 mg/kg body weight) caused reduction of FBG after two weeks of treatment (p < 0.010), but this was not sustained. The aqueous extract showed no reduction of FBG in diabetic rats. CONCLUSION: The aqueous extract of p alliacea demonstrated a hyperglycaemic effect in normoglycaemic rats and showed no hypoglycaemic activity in diabetic rats. The hexane extract caused no hypoglycaemic action in normal rats and failed to sustain an initial hypoglycaemic action in diabetic rats. This study presents evidence that does not support significant hypoglycaemic activity of p alliacea; this could hold significant implications for its use in ethno-traditional medicine.

OBJETIVO: Petiveria alliacea (p alliacea) tiene uso etnotradicional como agente hipoglicémico en Jamaica, y todavía requiere ser validado científicamente. Por lo tanto, extractos de las partes aéreas de la planta fueron evaluados en relación con su actividad hipoglicémica en ratas normoglicémicas y diabéticas. MÉTODOS: Extractos acuosos y extractos de hexanos preparados a partir de hojas de p alliacea fueron sometidos a prueba a fin de detectar su actividad hipoglicémica. Se evaluó el efecto de una administración aguda de los extractos (200 y 400 mg/kg de peso corporal) en ratas normoglicémicas. Además, se evaluó el efecto hipoglicémico de la administración subcrónica en ratas con diabetes inducida por estreptozotocina. La glucosa en sangre fue registrada usando un glucómetro y tiras reactivas. Los datos se analizaron mediante la prueba t de Student (p < 0.05). RESULTADOS: Los extractos acuosos y los extractos de hexano no mostraron reducción significativa alguna de la glucemia en ayunas (GA), ni tampoco ninguna mejora significativa de la tolerancia a la glucosa en ratas normales. El extracto acuoso (400 mg/kg de peso corporal) aumentó la GA de 4,75 ± 0,28 mmol/L a 5,88 ± 0,46 en comparación con el control (p < 0.001). En las ratas diabéticas, el extracto de hexano (400 mg/kg de peso corporal), trajo por consecuencia la reducción de GA tras dos semanas de tratamiento (p < 0.010), pero este efecto no se mantiene. El extracto acuoso no mostró ninguna reducción de GA en las ratas diabéticas. CONCLUSIÓN: El extracto acuoso de p alliacea mostró un efecto hiperglicémico en las ratas normoglicémicas, y no mostró ninguna actividad hipoglicémica en las ratas diabéticas. El extracto de hexano no produjo ninguna acción hipoglicémica en ratas normales, y no mantuvo la acción hipoglicémica inicial en las ratas diabéticas. Este estudio presenta evidencias que no respaldan una actividad hipoglicémica significativa de p alliacea, lo cual podría tener importantes implicaciones para su uso en la medicina etnotradicional.

Co-administration of trientine and flaxseed oil on oxidative stress, serum lipids and heart structure in diabetic rats.

The administration of flaxseed oil or flaxseed oil plus trientine in diabetic rats reduced triglyceride, very low density lipoprotein, and total cholesterol. Furthermore, the combined treatment significantly increased superoxide dismutase activity and attenuated serum Cu2+. The results suggest that the administration of flaxseed oil plus trientine is useful in controlling serum lipid abnormalities, oxidative stress, restoring heart structure, and reducing serum Cu2+ in diabetic rats.

Aqueous extract of Allium sativum L bulbs offer nephroprotection by attenuating vascular endothelial growth factor and extracellular signal-regulated kinase-1 expression in diabetic rats.

To investigate the nephroprotective effect of garlic and elucidate the mechanism by which it prevents the progression of diabetic nephropathy in diabetic rats, diabetes was induced by a single ip injection of streptozotocin (45 mg/kg body weight). Garlic extract (500 mg/kg body weight) and aminoguanidine (1 g/L) were supplemented in the treatment groups. Histopathological examination using H&E, PAS staining and the immunohistochemical analysis of vascular endothelial growth factor (VEGF) and extracellular signal-regulated kinase-1 (ERK-1) expression were performed on kidney sections at the end of 12 weeks. Significant change in both, the urine and serum biochemistry confirmed kidney damage in diabetic animals which was further confirmed by the histological changes such as mesangial expansion, glomerular basement membrane thickening, glycosuria and proteinuria. However, the diabetic animals treated with garlic extract showed a significant change in urine and serum biochemical parameters such as albumin, urea nitrogen and creatinine compared to that of diabetic rats. Further, the garlic supplemented diabetic rats showed a significant decrease in the expression of VEGF and ERK-1 compared to diabetic rats, attenuating mesangial expansion and glomerulosclerosis. Thus, garlic extract rendered nephroprotection in diabetic rats.

Inibição da expressão de ciclooxigenase 2 em feridas cutâneas de camundongos NOD submetidos à terapia a laser de baixa intensidade / Inhibition of cyclooxygenase 2 expression in NOD mice cutaneous wound by low-level laser therapy

CONTEXTO: A terapia a laser de baixa intensidade (LLLT) tem sido relatada como importante moduladora da cicatrização de feridas cutâneas aumentando a proliferação fibroblástica associada ao aumento da expressão da citocina fator transformador de crescimento- β2 (TGF-βB2). OBJETIVO: No presente estudo foram avaliados os efeitos da LLLT sobre a expressão da enzima ciclooxigenase 2 (COX2) no sítio do reparo tecidual utilizando o modelo experimental com camundongos diabéticos não obesos (NOD) para estudar a cicatrização de feridas cutâneas. MÉTODOS: Foram utilizados 30 camundongos NOD, destes 14 ficaram diabéticos e foram divididos em dois grupos: o grupo I (n=7) foi submetido a um procedimento cirúrgico de feridas cutâneas e o grupo II (n=7) foi submetido a um procedimento cirúrgico de feridas cutâneas e tratados com LLLT. O grupo II foi submetido à LLLT nos seguintes parâmetros: 15 mW de potência, dose de 3,8 J/cm² e tempo de aplicação de 20 segundos. Após sete dias do ato cirúrgico e após aplicação do laser, os animais foram eutanasiados com sobredose de anestesia e amostras das feridas foram colhidas para posterior análise histopatológica, histomorfométrica e imuno-histoquímica. RESULTADOS: A LLLT promoveu a inibição da expressão da COX2 em feridas cutâneas de camundongos diabéticos. CONCLUSÃO: Em conjunto, os resultados sugeriram que a LLLT é capaz de modular negativamente a expressão da enzima COX2 contribuindo para o controle da resposta inflamatória em feridas cutâneas de camundongos NOD.

BACKGROUND: Low-level laser therapy (LLLT) has been reported to modulate the healing of wounds by inducing an increase in fibroblast number associated with increased expression of the cytokine transforming growth factor-β2 (TGF-β2). OBJECTIVE: In the present study, the effect of LLLT on expression of COX2 at the site of tissue repair was evaluated, using an experimental model with non obese diabetic mice (NOD) to study cutaneous wound healing. METHODS: Thirty NOD mice were used, of which 14 were diabetic and were divided into two groups: group I (n=7) underwent a surgical procedure of skin wounds and group II (n=7) underwent a surgical procedure of skin wounds and treated with LLLT. Group II was submitted to LLLT in the following parameters: 15 mW of power, dose of 3.8 J/cm² and exposure time of 20 seconds. Seven days after surgery and after laser application, animals were euthanized with an overdose of anesthesia and tissue samples were collected for subsequent histological analysis, histomorphometry and immunohistochemistry. RESULTS: The LLLT has promoted the inhibition of COX2 expression in skin wounds in mice diabetic. Taken together the results suggest that LLLT modulate the expression of COX2 improved the control of inflammatory reaction in cutaneous wound lesions in NOD mice. CONCLUSION: Taken together, the results suggested that LLLT is able to negatively modulate the expression of COX2 enzyme contributing to the inflammatory response in cutaneous wounds in NOD mice.

Diabetes-induced prefrontal nissl substance deficit and the effects of neem-bitter leaf extract treatment / Diabetes inducida por déficit prefrontal de sustancia de nissl y el efecto del tratamiento con extracto de hoja de neem amargo

Cognitive dysfunction is reportedly associated with poorly-managed diabetes mellitus. In this study, we report the effect of oral treatment with combined leaf extract (CLE) of neem and bitter leaf on the prefrontal cortex of diabetic Wistar rats. Adult male Wistar rats were randomized to one of the following groups: control, diabetic (STZ-induced), STZ + CLE, STZ + metformin and CLE only. At euthanasia, paraffin sections of the prefrontal cortex were stained with cresyl fast violet; while malondialdehyde (MDA) and glutathione peroxidase (GPx) were assayed in prefrontal homogenates. Oral CLE produced normoglycemia in the treated hyperglycaemic rats. Besides, Nissl-stained prefrontal sections showed no morphologic deficits in all the groups except the untreated diabetic rats. In the latter, there was weak Nissl staining, while prefrontal MDA was significantly high at euthanasia, compared with the control and CLE-treated rats (P<0.05). This study showed that untreated diabetes mellitus is associated with prefrontal Nissl body deficit and oxidative stress in Wistar rats. The absence of these deficits in CLE-treated rats suggests a neuroprotective effect of the extract in streptozotocin-induced diabetic rats. This may improve the cognitive function of the prefrontal cortex in diabetes mellitus.

La disfunción cognitiva es presuntamente asociada con un mal manejo de la diabetes mellitus. En este estudio, se presenta el efecto del tratamiento oral combinado con extracto de hoja (CLE) de hoja de neem amarga sobre la corteza prefrontal de ratas Wistar con diabetes. Las ratas Wistar adultas fueron asignadas al azar a uno de los siguientes grupos: control, diabetes (STZ inducida), STZ + CLE, STZ + metformina y CLE. Después de la eutanasia, los cortes de parafina de la corteza prefrontal se tiñeron con violeta de cresil rápido, mientras que el malondialdehído (MDA) y la glutatión peroxidasa (GPx) fueron analizadas en homogenizados prefrontales. El CLE produce normoglucemia en las ratas hiperglucémicas tratadas. Además, las secciones prefrontales teñidas para Nissl no muestran ningún déficit morfológico en todos los grupos excepto en las ratas diabéticas sin tratamiento. En este último caso, hubo una tinción de Nissl débil, mientras que la MDA prefrontal fue significativamente más alta en comparación con los grupos de ratas control y las tratadas con CLE (p <0,05). Este estudio mostró que la diabetes mellitus no tratada se asocia con déficit prefrontal de cuerpos de Nissl y estrés oxidativo en ratas Wistar. La ausencia de estos déficits en las ratas tratadas CLE, sugiere un efecto neuroprotector del extracto en ratas diabéticas inducidas por estreptozotocina. Esto puede mejorar la función cognitiva de la corteza prefrontal en la diabetes mellitus.

Plasma concentrations and placental immunostaining of interleukin-10 and tumornecrosis factor-α as predictors of alterations in the embryo-fetal organism and the placental development of diabetic rats

Interleukin-10 (IL-10) appears to be the key cytokine for the maintenance of pregnancy and inhibits the secretion of inflammatory cytokines such as tumor necrosis factor-α (TNF-α). However, there are no studies evaluating the profile of these cytokines in diabetic rat models. Thus, our aim was to analyze IL-10 and TNF-α immunostaining in placental tissue and their respective concentrations in maternal plasma during pregnancy in diabetic rats in order to determine whether these cytokines can be used as predictors of alterations in the embryo-fetal organism and in placental development. These parameters were evaluated in non-diabetic (control; N = 15) and Wistar rats with streptozotocin (STZ)-induced diabetes (N = 15). At term, the dams (100 days of life) were killed under anesthesia and plasma and placental samples were collected for IL-10 and TNF-α determinations by ELISA and immunohistochemistry, respectively. The reproductive performance was analyzed. Plasma IL-10 concentrations were reduced in STZ rats compared to controls (7.6 ± 4.5 vs 20.9 ± 8.1 pg/mL). The placental scores of immunostaining intensity did not differ between groups (P > 0.05). Prevalence analysis showed that the IL-10 expression followed TNF-α expression, showing a balance between them. STZ rats also presented impaired reproductive performance and reduced plasma IL-10 levels related to damage during early embryonic development. However, the increased placental IL-10 as a compensatory mechanism for the deficit of maternal regulation permitted embryo development. Therefore, the data suggest that IL-10 can be used as a predictor of changes in the embryo-fetal organism and in placental development in pregnant diabetic rats.

Antidiabetic and hypolipidemic effects of different fractions of coccinia cordifolia L. on normal and streptozotocin-induced diabetic rats

The present study was carried out to observe the antidiabetic and hypolipidemic effects of petroleum-ether, ethyl acetate and chloroform fractions isolated from ethanolic extract of the leaves of Coccinia cordifolia Linn. [150 mg/kg body weight] on normal and streptozotocin [STZ]-induced diabetic rats for one day experiment. Single doses [150 mg/kg, i.p.] of C. cordifolia extracts were given to normal and diabetic rats. The fasting blood glucose [FBG], serum triglyceride [TG] and serum total cholesterol [TC] levels were investigated in normal and STZ-diabetic rats on 0, 1, 2, 3, 6, 10, 16, and 24[th] hours. In normoglycemic rats the pet-ether and ethyl acetate fractions of C. cordifolia reduced blood glucose level significantly [39.66% and 40.68% at 16[th] and 24[th] hour respectively]. In the STZ-diabetic rats pet-ether and ethyl acetate fractions also reduced blood glucose level significantly [50.39% and 50% at 10[th] and 24[th] hour respectively]. Ethyl acetate fraction is most effective which reduced total cholesterol level by 31.04% and 36.69% in normal and STZ-diabetic rats respectively. Ethyl acetate fraction reduced triglyceride level by 43.82% and 42.01% in normal and STZ-diabetic rats respectively. Our results indicate that pet-ether and ethyl acetate fractions of C. cordifolia have potentiality against diabetes

effect of oral administration of carum carvi on weight, serum glucose, and lipid profile in streptozotocin-induced diabetic rats

To evaluate the effect of oral administration of caraway [Carum carvi] on the blood glucose level, lipid profile, and the weight of diabetic rats. This investigation was carried out in Ahvaz University of Medical Sciences, Ahvaz, Iran between April and June 2010. Twenty-four male Wistar rats weighing 200-250 g were randomly divided into 3 groups: normal, diabetic, and caraway treated diabetic groups and were studied for 3 weeks. Diabetes was induced by intraperitoneal injection of 60 mg/kg body weight streptozotocin. Caraway was given orally at a dose of 1g/kg body weight daily, and the body weight of animals was measured every day. Blood samples were collected and blood glucose levels and lipid profile were determined. The results showed that oral administration of caraway caused a significant decrease in blood glucose level of treated rats [p=0.001] and alleviated their body weight loss [p=0.037]. Furthermore, it caused significant decrease in total cholesterol [p=0.036], and low-density lipoprotein cholesterol levels [p=0.001] in the treated animals compared with the diabetic control rats, and with no significant change in triglyceride and high-density lipoprotein cholesterol levels. Caraway has both antihyperglycemic and hypolipidemic activity in diabetic rats. Nevertheless, it is not recommended before further investigations in animals and humans

Effect of Aspirin on the Expression of Hepatocyte NF-kappaB and Serum TNF-alpha in Streptozotocin-Induced Type 2 Diabetic Rats

Aspirin is a kind of anti-inflammatory drug and may be used to reverse hyperglycemia, hyperinsulinemia, and dyslipidemia by improving insulin resistance. We hypothesized that aspirin improves insulin resistance in type 2 diabetes by inhibiting hepatic nuclear factor kappa-beta (NF-kappaB) activation and serum tumor necrosis factor-alpha (TNF-alpha). Adult male Wistar rats were randomly divided into four groups: control, untreated diabetic, diabetic treated with metformin (100 mg/kg/day), and diabetic treated with aspirin (120 mg/kg/day). Diabetes was induced by high-fat feeding and a low dose of streptozotocin (30 mg/kg). After treatment, plasma glucose, insulin, lipids, free fatty acids (FFAs) concentrations and serum TNF-alpha were determined. The expression of NF-kappaB in hepatocytes was analyzed by immunohistochemistry and western blot. The results showed administration of aspirin caused no significant lowering in fasting glucose level but significant reduction of hepatic NF-kappaB expression and serum TNF-alpha level with improved insulin resistance compared to the diabetic group. The relevant analysis showed positive correlation between the expression of homeostasis model assessment-insulin resistance (HOMA-IR) and NF-kappaB (r = 0.799, P < 0.01); HOMA-IR and serum TNF-alpha (r = 0.790, P < 0.01). It is concluded that aspirin improves insulin resistance by inhibiting hepatic NF-kappaB activation and TNF-alpha level in streptozotocin-induced type 2 diabetic rats.

Effects of diabetes on myocardial capillary density and serum angiogenesis biomarkers in male rats

INTRODUCTION: Cardiovascular disease is one of the main causes of mortality and morbidity in diabetic patients. This study evaluated the effects of diabetes on myocardial capillary density and several serum angiogenic factors including nitric oxide, vascular endothelial growth factor, and soluble vascular endothelial growth factor receptors. METHODS: Twelve male rats were divided into two groups: control and diabetic (n = 6 each). Diabetes was induced with a single dose of streptozotocin (50 mg/kg). After 21 days, capillary density in the myocardial tissue was evaluated using immunohistochemical staining and is reported as capillaries per mm². Blood samples were collected before and after the induction of diabetes. RESULTS: In the diabetic group, serum nitric oxide and soluble vascular endothelial growth factor receptor 2 concentrations were lower than the levels in the control group, while the level of soluble vascular endothelial growth factor receptor 1 was significantly higher. There was no significant change in the serum vascular endothelial growth factor concentration between the diabetic and control groups; however, the ratio of vascular endothelial growth factor to vascular endothelial growth factor receptor 1 was significantly lower in the diabetic animals. The myocardial capillary density was also lower in the diabetic group compared with the control group (1549 ± 161 vs. 2156 ± 202/mm², respectively). CONCLUSION: Reduced serum nitric oxide and vascular endothelial growth factor receptor 2 levels, increased serum vascular endothelial growth factor receptor 1 levels and a lower vascular endothelial growth factor to vascular endothelial growth factor receptor 1 ratio may be responsible for the decreased myocardial capillary density in diabetic rats.

Hepatics alterations and genotoxic effects of Croton cajucara Benth (SACACA) in diabetic rats / Alterações hepáticas e efeitos genotóxicos do Croton cajucara Benth (SACACA) em ratos diabéticos

CONTEXT: Croton cajucara Benth is a plant found in Amazonia, Brazil and the bark and leaf infusions of this plant have been popularly used to treat diabetes and hepatic disorders. OBJECTIVES: This study investigated effects hepatics alterations and genotoxic and antidiabetic effect of Croton cajucara Benth bark extracts treatment in streptozotocin-induced diabetic rats. METHODS: Male Wistar rats were divided into six groups: control rats; control rats treated with Croton cajucara Benth extract during 5 and 20 days; diabetic rats, and diabetic rats treated with Croton cajucara Benth during 5 and 20 days. Diabetes was induced by a single intraperitoneal injection of streptozotocin (70 mg/kg). Eight weeks later we measured glucose, triglyceride, cholesterol and hepatic transaminases on blood. The bone marrow micronucleus assay was used to assess the genotoxic activity of Croton cajucara Benth. RESULTS: Treatment with aqueous extrat of Croton cajucara was able to significantly reduce levels of triglycerides in diabetic animals, however, did not modify significantly the levels of glucose and cholesterol in these animals. There was no significant elevation in liver transaminases in the control group treated with Croton cajucara Benth, as there was no genotoxic effect of treatment in this model. Our results did not show a significant effect on glucose and cholesterol reduction, the treatment was able to significantly reduce triclycerides plasmatic level. There was no significant alterations on hepatic transferase in the animals from the control group treated with Croton cajucara Benth. It was observed no genotoxic effect of the treatment in the model studied. CONCLUSION: In this study Croton cajucara bark extract showed absence of hepatotoxicity in this animal model and presented a hypolipidemic activity, and could be used to reverse dyslipidemia associated with diabetes and to prevent the cardiovascular complications that are very prevalent in diabetic patients.

CONTEXTO: Croton cajucara Benth é uma planta encontrada na Amazônia, Brasil. Infusões da casca e folhas desta planta são utilizadas popularmente no tratamento de diabetes e doenças hepáticas. OBJETIVOS: Este estudo investigou as alterações hepáticas e os efeitos genotóxicos da casca do extrato do Croton cajucara Benth em animais diabéticos induzidos por estreptozotocina. MÉTODOS: Ratos Wistar machos foram divididos em seis grupos: ratos controle, ratos controle tratados com extrato de Croton cajucara Benth durante 5 e 20 dias, ratos diabéticos e diabéticos tratados com Croton cajucara Benth durante 5 e 20 dias. O diabetes foi induzido por uma única injeção intraperitonial de estreptozotocina (70 mg/kg). Oito semanas mais tarde foram medidos os níveis de glicose, triglicerídios, colesterol e transaminases hepáticas no sangue. O teste do micronúcleo da medula óssea foi utilizado para avaliar a atividade genotóxica do Croton cajucara Benth. RESULTADOS: O tratamento com o extrato aquoso do Croton cajucara foi capaz de reduzir significativamente os níveis plasmásticos dos triglicerídios nos animais diabéticos, porém, não modificaram significativamente os níveis de glicose e colesterol nesses animais. Não houve elevação significativa nas transaminases hepáticas nos animais do grupo controle tratadas com Croton cajucara Benth, assim como também não houve efeito genotóxico do tratamento, no modelo estudado. CONCLUSÃO: O extrato aquoso da casca do Croton cajucara Benth foi hipolipemiante, sugerindo seu uso para prevenir as dislipidemias encontradas em pacientes diabéticos.