Intravenous Administration Of Alloxan Research Articles

Diabetes triggers the loss of tooth structure associated to radiographical and histological dental changes and its evolution to progressive pulp and periapical lesions in rats

ObjectivesThe aim of this study was to evaluate the putative influence of diabetes without metabolic control in the loss of tooth structure as well as histological changes in dentin and pulp tissue in rats. DesignDiabetes was induced in Wistar rats (n=25) by intravenous administration of alloxan (42mg/kg). Diabetic and non-diabetic control rats were evaluated at 1, 3, 6, 9 and 12 months of follow-up. In order to evaluate the presence and progression of dental caries and periapical lesions, hemimandibles were removed and submitted to radiographical, histological, and morphometrical procedures. ResultsDental caries were detected after radiographical and histological evaluations in diabetic group from the third month of diabetes onset, increasing gradually in frequency and severity in periods. Diabetic rats dental pulps also presented significant reduction in volume density of collagen fibers and fibroblasts at third month, parallel with a trend towards the increase in inflammatory cells volume density. Diabetic rats presented a generalized pulp tissue necrosis after 6 months of diabetes induction. Moreover, periapical lesions were not detected in control group, while these lesions were observed in all rats after 3, 6, 9, and 12 months of diabetes induction. ConclusionsUncontrolled diabetes seems to trigger the loss of tooth structure, associated to histological dental changes and mediates its evolution to progressive severe pulp and periapical lesions in rats. Therefore, diabetes may be considered a very important risk factor regarding alterations in dental pulp, development of dental caries, and periapical lesions.

Hypoglycemic and Hypolipidemic Potential of a High Fiber Diet in Healthy versus Diabetic Rabbits

The aim of this study was to investigate potential hypoglycaemic and hypolipidemic effects of Plantago ovata husk included in the diet, in healthy and diabetic rabbits. We also examined the effects of this fiber in other biochemical parameters. Two groups of 18 rabbits were used. The first group was fed with standard chow and the second with chow supplemented with Plantago ovata husk (3.5 mg/kg/day). On day 14 diabetes mellitus was induced by the intravenous administration of alloxan (80 mg/kg). After an oral glucose load (3 g), glucose, insulin, and other biochemical parameters were determined on day 14 (healthy rabbits) and on day 28 (diabetic rabbits). In healthy rabbits, fiber did not modify glucose or insulin levels but decreased significantly total cholesterol, LDL-cholesterol, atherogenic index, and glycosylated hemoglobin. In diabetic rabbits, fiber was more beneficial in mild diabetics than in severe diabetics with significant decreases in glucose levels and increases in insulin concentrations. In these animals fiber caused an important reduction in cholesterol, indicating a beneficial effect of Plantago ovata husk in diabetic rabbits. Although further studies in patients are necessary, we think that Plantago ovata husk offers interesting perspectives to be administered to patients with diabetes mellitus.

Effects of insulin‐like growth factor I on alveolar bone remodeling in diabetic rats

Diabetes is a chronic hyperglycemic disorder and results in a tendency to develop osteoporosis. Furthermore, the delayed healing of tooth-extraction wounds, the activation of alveolar resorption and the suppressed formation of bone around implants are difficult for dentists to resolve. In diabetes, insulin-like growth factor I (IGF-I) appears to enhance the differentiation of osteoblasts and to activate the mineralization of bone. Hence, the aim of this study was to investigate the effects of insulin-like growth factor I on the remodeling of alveolar bone in diabetic rats. Diabetes was induced in 40 male Sprague-Dawley rats by intravenous administration of alloxan. The teeth of the rats were extracted to investigate remodeling of alveolar bone. Insulin-like growth factor I was administered, via intraperitoneal injection, to diabetic rats following tooth extraction. The remodeling of alveolar bone was determined using radiographic data, histological analyses and tetracycline fluorescence labeling. Compared with the control group, diabetes decreased alveolar bone formation. The height of alveolar bone and the bone-formation rate was significantly lower in the untreated diabetic group than in the control group or in the treated rats. Treatment with insulin-like growth factor I not only regulated abnormal blood glucose levels but also increased the height of the alveolar bone and increased the bone-formation rate relative to the results in diabetic animals. Furthermore, the expression of glucose transporter-1, the main transporter of glucose, was changed by hyperglycemia. The results suggest that insulin-like growth factor I treatment increases the volume of newly formed bone following tooth extraction and normalizes the expression of glucose transporter-1 in diabetic rats, which may play an important role in bone formation and mineralization.

Exercise and spirulina control non-alcoholic hepatic steatosis and lipid profile in diabetic Wistar rats.

BackgroundDiabetes mellitus is associated with metabolic dysfunctions, including alterations in circulating lipid levels and fat tissue accumulation, which causes, among other pathologies, non-alcoholic fatty liver disease (NAFLD).Aim of the studyThe objective of this study was to analyse the effects of physical exercise and spirulina intake on the control of NAFLD in diabetic Wistar rats.MethodsDiabetes was induced in the animals through intravenous administration of alloxan. The rats were divided into four groups: Diabetic Control (DC) - diabetic rats fed with a control diet and no physical exercise; Diabetic Spirulina (DS) - diabetic rats fed with a diet that included spirulina; Diabetic Spirulina and Exercise (DSE) - diabetic rats fed with a diet that included Spirulina and that exercised; and Diabetic Exercise (DE) - diabetic rats fed with a control diet and that exercised.ResultsThe groups DS, DSE, and DE presented lower plasma concentrations of LDL cholesterol than DC, as well as lower levels of total liver lipids in groups DS, DSE, and DE in comparison to DC.ConclusionThus, spirulina appears to be effective in reducing total circulating levels of LDL-cholesterol and hepatic lipids, alone or in conjunction with physical exercise in diabetic rats.

Alloxan-Induced Diabetes Triggers the Development of Periodontal Disease in Rats

BackgroundPeriodontal disease in diabetic patients presents higher severity and prevalence; and increased severity of ligature-induced periodontal disease has been verified in diabetic rats. However, in absence of aggressive stimuli such as ligatures, the influence of diabetes on rat periodontal tissues is incompletely explored. The aim of this study was to evaluate the establishment and progression of periodontal diseases in rats only with diabetes induction.Methodology/Principal FindingsDiabetes was induced in Wistar rats (n = 25) by intravenous administration of alloxan (42 mg/kg) and were analyzed at 1, 3, 6, 9 and 12 months after diabetes induction. The hemimandibles were removed and submitted to radiographical and histopathological procedures. A significant reduction was observed in height of bone crest in diabetic animals at 3, 6, 9 and 12 months, which was associated with increased numbers of osteoclasts and inflammatory cells. The histopathological analyses of diabetic rats also showed a reduction in density of collagen fibers, fibroblasts and blood vessels. Severe caries were also detected in the diabetic group.Conclusions/SignificanceThe results demonstrate that diabetes induction triggers, or even co-induces the onset of alterations which are typical of periodontal diseases even in the absence of aggressive factors such as ligatures. Therefore, diabetes induction renders a previously resistant host into a susceptible phenotype, and hence diabetes can be considered a very important risk factor to the development of periodontal disease.

Adoptive Transfer of Mast Cells Abolishes the Inflammatory Refractoriness to Allergen in Diabetic Rats

Mast cells are pivotal secretory cells primarily implicated in allergen-evoked inflammatory responses and are downregulated following experimental chemical diabetes. Here we tested the hypothesis that a decrease in the number and reactivity of mast cells would account for the hyporesponsiveness of diabetic rats to allergen-induced inflammation. We found that the anaphylactic release of histamine from sensitized ileum, trachea and skin tissues was clearly reduced in rats turned diabetic via intravenous administration of alloxan. Likewise, actively and passively sensitized diabetic rats mounted a weaker allergen-evoked pleural mast cell degranulation and protein extravasation, as compared to sensitized nondiabetic animals, which paralleled a marked reduction in the mast cell population in the pleural cavity. The number of mast cells enumerated in the mesentery from diabetic rats was also clearly reduced. The allergen-evoked plasma leakage in diabetic rats was restored by the transfer of mast cells from sensitized nondiabetic rats. Moreover, the adoptive transfer of sensitized mast cells from diabetics to naive animals led to a lower allergen-induced exudation as compared to the response noted after the transfer of sensitized naive mast cells. Purified mast cells from diabetic rats were hyporesponsive to antigen and compound 48/80 stimulation in vitro as attested by histamine release. Thus, our results show that the phenomenon of refractoriness of diabetic animals to allergen challenge appears to be accounted for by a reduction in the number and reactivity of mast cells.

Experimental diabetes in lactating sheep: effects of alloxan on plasma insulin, glucose, glucose kinetics and milk characteristics.

After intravenous administration of alloxan (50 mg kg-1 liveweight) to lactating ewes, there were triphasic changes in plasma glucose and insulin. Almost immediately, plasma insulin decreased and hyperglycaemia occurred, then, between c. 5-12 h, insulin increased and ewes became hypoglycaemic. Thereafter, insulin decreased and glucose increased from c. 20 h after alloxan and the diabetic state was established. Changes in glucose production and utilization correlated with changes in plasma glucose. Exogenous insulin was administered from 30 h after alloxan, and it took some 2 weeks to stabilize ewes. During this period, when mild hyperglycaemia persisted, milk yields and feed intakes were decreased but milk fat content was elevated. Once ewes were stabilized, plasma glucose, milk yield, feed intake and milk fat content returned to levels prior to alloxan. These observations are consistent with insulin playing a role in the aetiology of the 'low milk fat syndrome' in the ruminant. It appears that the alloxan-treated, insulin-stabilized ewe would be a useful model for studying the role of insulin during lactation, but it is necessary to allow time for animals to overcome effects of administration of alloxan.

Amygdaloid kindling in alloxan-diabetic rats.

Wistar rats, made diabetic by intravenous administration of alloxan, 40 mg/kg, were submitted to amygdala kindling. The EEG and behavioral responses elicited by stimulating the amygdala nuclei in these animals were compared with those observed in control rats. Alloxan-treated rats required more stimulation to kindle, had increased duration of afterdischarges (AD), presented intense interictal spiking, and exhibited greater number of wet-dog shakes than controls. Although the AD threshold was not different between control and experimental rats, the above results seem to indicate an increase in the local epileptic susceptibility represented by longer ADs. On the other hand, this increased local discharge seems to be unable to access the generalization mechanism, which can be verified by the increased kindling rate. Hyperosmolarity, pH alterations, or other generalized metabolic changes frequently associated with diabetes could be implicated in these results.

Unchanged pulmonary capillary filtration coefficients after Escherichia coli endotoxin infusion

The pulmonary capillary filtration coefficient ( K f,c) was measured in intact, anesthetized dogs before and after the intravenous administration of alloxan and E. coli endotoxin. The method used to measure K f,c was that of determining the capillary filtration rate by analyzing the weight transient following a change in capillary pressure ( ΔP c) and dividing the initial filtration rate by ΔP c. In four dogs given 75 mg/kg of alloxan, the K f,c increased 10-fold. This indicated that the capillary membranes were damaged by the alloxan and that, by using this method of measuring K f,c, changes in K f,c were easily detected. The K f,c, measured after a 3-hr continuous infusion of a total of 4 mg/kg of E. coli endotoxin [0.35 ± 0.21 (SD) ml/min/mm Hg/100g], was not different from the value found in the same animals before the endotoxin (0.33 ± 0.29). Since the K f,c is a sensitive indicator of capillary membrane pore size, these results strongly suggest that E. coli infusion did not damage the pulmonary capillary membrane.

Metabolic effects of insulin on rat kidney after inhibiting degradation of the hormone.

The intravenous administration of alloxan (20 mg/100 g) to intact rats causes marked inhibition of destruction of 135I insulin. Either “functional” evisceration or nephrectomy results in 40% diminution in the rate of insulin destruction and prior alloxan injection to both groups of animals causes still further reduction in the rate of insulin degradation. A procedure of combined “functional” evisceration and nephrectomy is followed by much reduced but still apparent insulin degradation, which is further inhibited by prior alloxan injection. Thus, alloxan administration appears to cause impairment of insulin degradation by liver, kidney and possibly other in vivo sites. Kidney slices obtained from alloxan injected animals and incubated in glucose or pyruvate buffer in the presence of insulin demonstrate insulin enhanced utilization of these substrates, whereas kidney slices from saline injected animals fail to demonstrate an insulin effect in vitro. These observations suggest a regulatory role between the rate of insulin degradation and the biologic effectiveness of insulin upon the kidney. (Endocrinology83: 1166, 1968)