A potential synbiotic product improves the lipid profile of diabetic rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cissus sicyoides (princess vine) in the long-term treatment of streptozotocin-diabetic rats

Leaf decoctions of Cissus sicyoides (princess vine) are taken widely as a popular remedy for diabetes mellitus in Brazil, where its common name is 'vegetal insulin'. However, there have been practically no attempts so far to determine scientifically whether it has antidiabetic effects and we decided to administer leaf decoctions, over extended periods, to normal and streptozotocin-diabetic rats, and investigate the effects of this treatment on the physiological and metabolic parameters that are altered in diabetic animals. The experimental model adopted was shown to be appropriate by running a parallel treatment with insulin, which led to expected improvements in several abnormal parameter values. The decoction treatment significantly reduced the intake of both food and fluid and the volume of urine excreted, as well as the levels of blood glucose, urinary glucose and urinary urea, in comparison with controls. Lipid metabolism was not affected by the treatment; nor was the level of hepatic glycogen in diabetic animals, which indicated that the mechanism responsible for the improvement in carbohydrate metabolism, observed in animals treated with the decoction, could not involve inhibition of glycogenolysis and/or stimulation of glycogenesis. The fact that normal animals treated with C. sicyoides exhibited no changes in any of the measured parameters suggests that its mode of action in diabetic animals does not resemble those of sulphonylurea or insulin. It may, however, act in a similar way to biguanide, via inhibition of gluconeogenesis.

Effects and toxicity of Eugenia punicifolia extracts in streptozotocin-diabetic rats

Extracts and decoctions of Eugenia jambolana Lam., Eugenia uniflora L., and Eugenia punicifolia (Humb., Bonpl. & Kunt) DC. are used in traditional medicine to treat diabetes mellitus. Although there have been reports that Eugenia jambolana and Eugenia uniflora have antidiabetic effects, no study has yet been made on Eugenia punicifolia . We investigated the effects of aqueous, butanol, and methanol extracts of Eugenia punicifolia leaves administered by gavage to streptozotocin-diabetic rats for 26 to 29 days. Body weight, food and fluid intake, urine volume, and urinary glucose and urea were evaluated every 7 days. At the end of the experiment, we measured serum cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides and bilirubin, hepatic glycogen and serum marker-enzymes (alanine and aspartate aminotransferases, alkaline phosphatase, gamma-glutamyltransferase, L-lactate dehydrogenase, creatine kinase, alpha-amylase, and angiotensin I converting enzyme). We found that in rats treated with the aqueous extracts, food and liquid intake, urinary volume, and body weight were all reduced, while for rats treated with the methanol extract, not only were liquid intake, urinary volume and body weight reduced, but urinary glucose and urea also decreased. Rats treated with the butanol extract showed no significant alterations in any of the parameters measured. Chronic treatment with extracts had no effect on the marker enzymes nor on serum bilirubin levels. The results indicate that aqueous extracts of Eugenia punicifolia leaves produced an anorexic effect and that methanol extracts had a beneficial effect on the diabetic state by improving carbohydrate and protein metabolism without provoking hepatobiliary, microvascular, muscular, or pancreatic toxic effects.

Anti-diabetic activity of Bauhinia forficata decoction in streptozotocin-diabetic rats

The effects of using Bauhinia forficata leaf decoction (150 g leaf/l water; 35.2+/-7.8 ml/100 g body weight mean daily dose) as a drinking-water substitute for about I month on streptozotocin-diabetes (STZ-diabetes) in male Wistar rats were investigated. The physico-metabolic parameters measured were: body weight, food and liquid intake, urinary volume, hepatic glycogen, serum triglycerides and cholesterol, plasma glucose, urinary glucose and urea, and the weight of epididymal and retroperitoneal adipose tissue and soleus and extensor digitorum longus muscles. The STZ-diabetic rats treated with decoction showed a significant reduction in serum and urinary glucose and urinary urea as compared to the STZ-diabetic control, no difference being seen between decoction-treated and -untreated non-diabetic rats. The other physico-metabolic factors showed no changes in treated STZ-diabetic rats. The improvement in carbohydrate metabolism seen in the rats treated with Bauhinia forficata decoction does not appear to be linked to the inhibition of glycogenolysis or the stimulation of glycogenesis nor does it appear to act in a way similar to insulin or the sulfonylureas, although it may act by the inhibition of neoglycogenesis in a manner similar to that of the biguanides. (C) 2002 Elsevier B.V. Ireland Ltd. All rights reserved.

Effect of oral vanadyl sulfate treatment on serum enzymes and lipids of streptozotocin-diabetic young rats

In this work we investigate the possible toxicity of vanadyl sulfate (VOSO4), a compound capable of reducing hyperglycemia, on the following serum enzymes of diabetic young rats: alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LD) and creatine kinase (CK), as well as its effects on serum lipids. We find that at a concentration of 1 mg/mL VOSO4 has no toxic effect on the liver and muscles of diabetics young rats. These findings suggest that VOSO4 may be an alternative to insulin in the near future, due to its low cost, low toxicity and ready availability.

Mechanisms for consideration for intervention in the development of organophosphorus-induced delayed neuropathy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Organophosphorus-induced delayed neuropathy: A simple and efficient therapeutic strategy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Neurophysiological patterns of ulnar nerve neuropathy in leprosy reactions

Background: Leprosy neuropathy, despite being primarily demyelinating, frequently leads to axonal loss. Neurophysiological examination of the nerves during Type 1 (T1R) and Type 2 reactions (T2R) may give some insight into the pathophysiological mechanisms.Methods: Neurophysiological examinations were performed in 28 ulnar nerves during a clinical trial of steroid treatment effectiveness, 19 patients with T1R and nine with T2R. The nerves were monitored during a period of 6 months; there were eight assessments per nerve, for a total of 224 assessments. Nine neurophysiological parameters were assessed at three sites of the ulnar nerve. The compound motor action potential amplitudes elicited at wrist, elbow and above, as well as the conduction velocity and temporal dispersion across the elbow, were chosen to focus on the changes occurring in the parameters at the elbow tunnel.Results and Conclusion: Neurophysiological changes indicating axonal and demyelinating processes during both T1R and T2R were detected across the elbow. Changes in demyelination, i.e. a Conduction Block, as a primary event present during T2R, occurring as an acute phenomenon, were observed regularly; in T1R Temporal Dispersion, a subacute phenomenon, was seen. During treatment remyelination occurred after both types of reactions.

Nonlinear methods of heart rate variability analysis in diabetes

Background: The autonomic dysfunction stands out among the complications associated to diabetes mellitus (DM) and may be evaluated through the heart rate variability (HRV), a noninvasive tool to investigate the autonomic nervous system that provides information of health impairments and may be analyzed by using linear and nonlinear methods. Several studies have shown that HRV measured in a linear form is altered in DM. Nevertheless, a few studies investigate the nonlinear behavior of HRV. Therefore, this study aims at gathering information regarding the autonomic changes in subjects with DM identified by nonlinear analysis of HRV.Methods: For that, searches were performed on Medline, SciELO, Lilacs and Cochrane databases using the crossing between the key-words: diabetic autonomic neuropathy, autonomic nervous system, diabetes mellitus and heart rate variability. As inclusion criteria, articles published on a period from 2000 to 2010 with DM type land type II population which assessed the autonomic nervous system by nonlinear indices HRV were considered.Results: The electronic search resulted in a total of 1873 references with the exclusion of 1623 titles and abstracts and from the 250 abstracts remaining, 8 studies were selected to the final analysis that completed the inclusion criteria.Conclusions: In general, the analysis showed that the nonlinear techniques of HRV allowed detecting autonomic changes in DM. The methods of nonlinear analysis are indicated as a possible tool to be used for early diagnosis and prognosis of autonomic dysfunction in DM.

Anastomotic healing in ileum and colon of alloxan-induced diabetic rats

OBJETIVO: Investigar se o diabetes mellitus pode alterar a força de ruptura (FR) e o conteúdo de colágeno em anastomoses realizadas no íleo e cólon de ratos. MÉTODOS: 300 ratos Wistar foram distribuídos por sorteio em 5 grupos experimentais com 60 animais cada: controle normal manipulado cirurgicamente (G1); normais controles submetidos a anastomoses no íleo (G2) e cólon (G3); ratos diabéticos submetidos a anastomoses no íleo (G4) e cólon (G5). Cada grupo foi dividido em 6 subgrupos com 10 ratos cada para sacrifícios com 0, 4, 7, 14, 21 e 30 dias após as operações. Os procedimentos cirúrgicos foram realizados 3 meses após a indução do diabetes com aloxana. A FR foi medida em todas anastomoses intestinais. Fragmentos de anastomoses do íleo e cólon foram retirados para dosagens de hidroxiprolina (HP) e proteína tecidual total (PT). RESULTADOS: A FR teve significante redução (P<0,05) nos grupos diabéticos G4 e G5, até 7 e 14 dias após a operação, respectivamente, quando comparada à observada nos grupos controles G2 e G3. Não foram observadas diferenças significantes nas dosagens de HP e PT em ratos diabéticos e controles, tanto operados no íleo como no cólon, em todos os momentos de avaliação. CONCLUSÃO: O diabetes conduz a alterações da força de ruptura de anastomoses intestinais durante a fase inicial da reparação da ferida cirúrgica, porém, este fato parece não estar relacionado à capacidade de sintetizar colágeno.

Reduction of podocytes number in late diabetic alloxan nephropathy: prevention by glycemic control

OBJETIVO: Avaliar o número de podócitos e espessamento da membrana basal glomerular (MBG) em ratos diabéticos com e sem controle glicêmico com 6 e 12 meses da indução. MÉTODOS: 100 ratos Wistar com 200-300g compuseram 6 grupos: Normal (N6, N12 - 25 animais) Diabético (D6,D12 - 25 animais) e diabético tratado com insulina 1,8 a 3,0 U/Kg e acarbose misturada a ração (50g para cada 100g de ração) (DT6 e DT12 - 25 animais). Aloxana foi ministrada via endovenosa na dose de 42mg/Kg. Peso, ingestão hídrica e diurese de 24 horas e glicemia e glicosúria foram determinados antes da inoculação, 7 e 14 dias após e mensalmente. No 14ª dia foi iniciado o tratamento. Três grupos de animais (N6, D6 e DT6) foram sacrificados no 6° mês e três grupos (N12, D12 e DT12), no 12ª mês sendo o tecido renal processado para estudo à microscopia eletrônica. RESULTADOS: A glicemia dos animais DT6 e DT12 diferiram significativamente, dos ratos D6 e D12, e não diferiram dos grupos N6 e N12. O número de podócitos do grupo DT6 não diferiu de N6 e D6 (mediana=11); o número de podócitos de DT12 (mediana=11) diferiu de D12 (mediana=8) e não diferiu de N12 (mediana=11). O espessamento da MBG de D6 (0,18 micrômetros) foi menor que D12 (0,29 micrômetros); de DT6 (0,16 micrômetros) foi menor que D6 (0,18 micrômetros) e de DT12 (0,26 micrômetros) foi menor que D12 (0,29 micrômetros). CONCLUSÃO: O controle da hiperglicemia preveniu o espessamento da MBG na nefropatia diabética aloxânica precoce (6 meses) e tardia (12 meses), e a diminuição do número de podócitos.

Effects of pancreas transplantation on oxidative stress in pulmonary tissue from alloxan-induced diabetic rats

Purpose. There is considerable evidence that cellular oxidative stress caused by hyperglycemia plays an important role in the genesis and evolution of chronic diabetic lesions. In this study, we determined the effectiveness of pancreas transplantation (PT) in preventing the imbalance caused by excessive production of reactive oxygen species over antioxidant defenses in lungs of rats rendered diabetic by alloxan injection.Methods. Sixty inbred male Lewis rats, weighing 250-280 g, were randomly assigned to 3 experimental groups: NC, 20 nondiabetic control rats; DC, 20 untreated diabetic control rats; and PT, 20 diabetic rats that received syngeneic PT from normal donor Lewis rats. Each group was further divided into 2 subgroups of 10 rats each which were killed after 4 and 12 weeks of follow-up. Plasma glucose, glycosylated hemoglobin, and insulin levels were determined in all rats. Lipid hydroperoxide (LPO) concentrations and enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were measured in the pulmonary tissue of all rats.Results. The DC rats showed elevated blood glucose and glycosylated hemoglobin levels, with insulin blood levels significantly lower than the NC rats (P < .001). They also showed significantly increased LPO concentrations in the lungs (P < .01) after 4 and 12 weeks of follow-up. In contrast, SOD, CAT, and GSH-Px antioxidant activities were significantly reduced in these periods (P < .01) 12 weeks after diabetes induction. Successful PT corrected all clinical and metabolic changes in the diabetic rats, with sustained normoglycemia throughout the study. Excessive lung LPO production and low SOD, CAT, and GSH-Px antioxidant activities were already back to normal 4 weeks after PT.Conclusion. PT can control oxidative stress in pulmonary tissue of diabetic rats. It may be the basis for preventing chronic diabetic lesions in lungs.

Evaluation of placental glycogen storage in mild diabetic rats

Purpose: To evaluate the placental glycogen storage and fetal development in the pregnancy of neonatally streptozocin-induced diabetic rats and to establish relation with glycemia and insulin levels. Methods: At the birth day, 147 female rats were randomly distributed in two experimental groups: 1) Non-diabetic Group (Control, n=45) - received the vehicle; 2) Diabetic Group (STZ, n=102) received 100 mg streptozocin/kg in neonatal period. At day 0 of pregnancy, adult female rats were included in the control group when presented glycemia below 120 mg/dL and, in the group STZ with glycemia between 120 and 300 mg/dL. At day 21 of pregnancy, blood samples were collected for glycemia and insulin determination, and placentas withdrawn for placental glycogen determination. The newborns (NB) were classified in small (SGA), appropriate (AGA) and large (LGA) for gestational age. Results: Rats STZ presented higher glycemia at days 0 and 14 of pregnancy. At end of pregnancy, rats STZ showed higher proportion of NB SGA and LGA; reduced rate of NB AGA and unaltered glycemia, insulin and placental glycogen determinations. Conclusion: Mild diabetes altered the maternal glycemia in the early pregnancy, impairing future fetal development, but it caused no alteration on insulin and placental glycogen determination, confirming that this glycemic intensity was insufficient to change glycogen metabolism.