No abstract available.
Alloxan* ; Animals ; Rats*

Cataracts often occur in diabetic patients or as a consequence of diabetes experimentally induced with alloxan or streptozotocin. In mammals, the transparency of the lens depends on its Ca++ level, and many researchers have proven experimentally that cataracts may occur in cases of increased lens calcium level. In 1981 Fleckenstein et al. were the first to demonstrate experimentally that the cause of cataracts in the alloxan induced diabetic rat is due to an increased lens calcium level, and this calcium induced cataract may be suppressed by the calcium channel blocker-verapamil which prevents lenticular calcium overload. However, they did not determine the mechanism of verapamif on the inhibitory action of lenticular calcium overload. In this experiment verapamil was administrated to control rats and to streptozotocin induced diabetic rats to discover by what mechanism verapamil prevents the occurrence of cataracts as a complication in experimental diabetic rats. The authors compared lens calcium level and measured active 45Ca efflux from the lens, Na+ - Ca++ exchange and Ca++ - ATPase activity in the lens between the control and experimental groups. Their conclusions are as follows: 1. The calcium level of the lens was significantly increased in SDR(Streptozotocin injected diabetic rat) as compared to NDC(Nondiabetic control rat), VNDC(Verapamil treated nondiabetic control rat) and SVDR(Streptozotocin injected verapamil treated diabetic rat). 2. Active 45Ca efflux across the lens membrane was significantly decreased in SDR as compared to NDC, VNDC and SVDR. 3. The Ca++ - ATPase activity was significantly suppressed in SDR as compared to NDC, VNDC and SVDR. 4. Verapamil had no influence on the Na+ - Ca++ exchange transport system in all groups of NDC, VNDC, SDR and SVDR. Thus, our results suggest that verapamil prevents the occurrence of cataracts in diabetic rats probably by controlling the Ca++ transport system in the lens membrane.
Adenosine Triphosphatases ; Alloxan ; Animals ; Calcium Channels ; Calcium* ; Cataract ; Humans ; Mammals ; Membranes ; Rats* ; Streptozocin ; Verapamil*

The approach and novelty of this scientific work was to formulate the appropriate Streptozotocin (STZ) and Alloxan dosage in different routes of administration to imply minimum mortality rate and high incidence of diabetes mellitus (DM) in the rat experiment model. Rats were randomly divided into STZ, Alloxan and control groups. 1-Alloxan group was divided into two subgroups: intraperitoneal (ip) subgroups which received a single dose of, 140, 120, 100 and 80 mg/kg; and the subcutaneous (sc) subgroups which received a single dose of, 120, 110, 100, 90, and 80 mg/kg. 2-STZ group was divided into four subgroups of ip route. The ip subgroup which received intraperitoneally a single dose of, 30, 35, 40 and 50 mg/kg. 3-The control group: This group received solo distilled water. The injection day was considered as the day zero. Blood glucose levels and mortality rate were recorded. Subsequently, 30 days after, the logistic regression modeling was used to evaluate the effect of the explanatory variables, the dose levels, and route approaches, on the probability of DM incidence, and mortality. According to the statistical logistic analysis for Alloxan, it is concluded that the minimum dosage needed to induce DM was 120 mg/kg by sc method (probability 0.712). In addition, the logistic analysis for STZ showed that the optimal dose-level for STZ was 40 mg/kg with ip with approximate induction of DM probability 0.764. Based on the data, male Wistar rats in which received a single dosage of Alloxan by sc injection at dose of 120 mg/kg showed the most desirable result of induction of type I DM; furthermore, those in which received STZ by ip injection at the dose of 40 mg/kg developed a persistent and optimal DM state characterized by high rate of DM induction and low- level of mortality.
Alloxan* ; Animals ; Blood Glucose ; Diabetes Mellitus* ; Humans ; Incidence ; Logistic Models ; Male ; Methods ; Mortality* ; Rats* ; Rats, Wistar ; Streptozocin* ; Water

Alloxan administration in rats is used as a model for non-insulin dependent diabetes mellitus (NIDDM). NIDDM is a multifactorial disease, characterized by hyperglycemia and lipoprotein abnormalities. In this study, we evaluated the antihyperglycemic and antihyperlipidemic effects of fermented Rhynchosia nulubilis (FRN) through the regulation of glucose uptake in alloxan-induced rats. Fermented R. nulubilis was administered orally for 28 d at 500 mg/kg of body weight. Body weight and food intake were monitored every day. Biochemical parameters were quantified after 4 week. In the diabetic + FRN group, body weight increased significantly and blood glucose concentrations decreased when compared to those of the diabetic group. After 2 hr of administration, the oral glucose tolerance test (OGTT) indicated a significant reduction in the diabetic + FRN group compared to diabetic group. The diabetic + FRN group experienced a significant reduction in total cholesterol, triglycerides, low density lipoprotein, coronary risk factors, and malondialdehyde concentrations, with significantly increased high density lipoprotein compared to those of diabetic group. These results demonstrate that fermented R. nulubilis possesses potent antihyperglycemic and antihyperlipidemic activity in alloxan-induced diabetic rats.
Alloxan ; Animals ; Blood Glucose ; Body Weight ; Cholesterol ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Eating ; Glucose ; Glucose Tolerance Test ; Hyperglycemia ; Lipoproteins ; Malondialdehyde ; Rats ; Risk Factors ; Triglycerides

The effect of alloxan-diabetic rat fed with normal, high fat, low protein and high protein diets on the rate of urea production and the activities of enzymes associated with the urea cycle (ornithine transcarbamoylase, E.C. 2.1.3.3, OTC; arginase, E.C. 3.5.5.1) have been studied in intact and isolated perfused liver. The amount of urea excretion was the highest in the high protein diet group. When each diet group was treated with alloxan, total urea excretion showed little differences between each diet group and its corresponding control group with the exception being in the normal diet group. However, the enzyme activity of OTC was increased significantly by alloxan treatment in low and high protein diet groups as compared to corresponding control groups. Similar results were obtained in arginase activity, although the magnitude of the change was less marked. In liver perfusion experiments on rats treated with alloxan, the amount of urea production and changes in OTC and arginase activity were very similar with those in the intact liver. These results suggest that alloxan treatment in normal diet group causes an increase in urea excretion both in intact and perfused liver regardless of changes in enzyme activities and total urea excretion, and enzyme activities are affected by changes in dietary components but the changes of enzyme activities may not correlate with total urea excretion.
Alloxan ; Animal ; Diabetes Mellitus, Experimental/metabolism* ; Dietary Fats/pharmacology* ; Dietary Proteins/pharmacology* ; In Vitro ; Liver/metabolism* ; Male ; Perfusion ; Rats ; Urea/metabolism* ; Urea/urine

PURPOSE: Diabetic women commonly reported decreased sexual arousal and a lack of vaginal lubrication. Genital arousal depends on the vaginal blood flow and the vaginal smooth muscle tone. The aim of this study was to investigate the effect of diabetes mellitus on the relaxation of the vaginal smooth muscles in the rabbit models. MATERIALS AND METHODS: New Zealand White female rabbits (3-3.5kg) were divided into two groups: control (n=5) and experimental (n=20). The experimental group received an intravenous injection of alloxan (100mg/kg). The development of diabetes was verified by measuring the body weight and blood glucose levels. After 12 weeks, the reactivity of the vaginal tissue from the control and diabetic animals was studied examined in the organ chambers. Vaginal The vaginal tissue was also processed immunohistochemically to determine the presence of the neuronal NOS isoform (n-NOS) in similar groups of rabbits. RESULTS: By After 12 weeks, five 5 of the 20 animals developed diabetes mellitus. The mean blood glucose level was significantly increased higher in the experimental group (340.8+/-116.9 mg/dl) compared to the control group (81.3+/-6.2mg/dl) (p=0.004). There was no significant difference in terms of the rRelaxation of vaginal tissue to electrical stimulation of the autonomic nerves, to the endothelium-dependent vasodilator acetylcholine and to the endothelium-independent vasodilator nitroprruside was not significantly different between the control and diabetic group. n-NOS immunoreactivity was also similar in both the control and diabetic groups. CONCLUSIONS: This The results suggest that diabetes mellitus may does not impair the neurogenic and endothelium-dependent relaxation of the rabbit vaginal smooth muscle. However, further intensive studies areinvestigation is needed to verify these results.
Acetylcholine ; Alloxan ; Animals ; Arousal ; Autonomic Pathways ; Blood Glucose ; Body Weight ; Diabetes Mellitus* ; Electric Stimulation ; Female ; Humans ; Injections, Intravenous ; Lubrication ; Muscle, Smooth* ; Neurons ; New Zealand ; Rabbits ; Relaxation* ; Vagina

This experiment was aimed to investigate the contractile responses of the fermoral artery to the electrical stimulation and the inhibitory effects of verapamil and papaverine on the electrical stimulation of the fermoral artery in the control (n=46) and the diabetic rabbits(n=40). Diabetic rabbits were made by and administration of alloxan (100 mg/kg) intravenously and sacrified 8 weeks later. Femoral arterial rings 3 mm in length were taken and mounted on the force-displacement transducer for the measurements of isometric tension. All experiments were done in the aerated (95% O2 with 5% CO2)biological chamber filled with Kreb's solution and the initial tension of 1.5g was applied to the rings. After 1 hour of equilibrium of the rings, the contractile responses of the electrical stimulation on the femoral arterial rings were taken without vasoactive drugs and then, under verapamil and papaverine solution. And we compared the morphologic findings of the vessels in the two groups in relation to the functional changes by transmission electron miroscopy. The results are as follows: 1. The contractile responses in the presence of verapamil or papaverine solutions to the electrical stimulation were lowed significantly in the fermoral arterial rings of the diabetic rabbits compared with that of the control rabbits (verapamil; 10M~10M: p<0.01, papaverine; 10M & 10M: p<0.01). 2. Transmission electron microphotographs showed many morphological differences of the femoral arteries between the control and the diabetic rabbits. These were irregularities of the internal elastic lamina and the hypertrophy of the cytoplasms of the smooth muscle cells. And also, there were many vacuoles in the cytoplasm of the endothelial cells, lateral to the internal elastic laminaes, and between the smooth muscle cells in the diabetic rabbit femoral artery. By this study, we found that the contractile responses of the femoral arterial rings to the electrical stimulation were decreased in the diabetic rabbits, and the vasodiatory effects of verapamil and papaverine on the electrically stimulated femoral arterial rings were also lowered in the diabetic rabbits compared with the control rabbits. These changes of the vasular responses of the diabetic vessel may be associated with morphological changes manifested by transmission electron microscopy or any other functional derangement of the vessels.
Alloxan ; Arteries ; Cytoplasm ; Electric Stimulation* ; Endothelial Cells ; Femoral Artery ; Hypertrophy ; Microscopy, Electron, Transmission ; Myocytes, Smooth Muscle ; Papaverine ; Rabbits ; Transducers ; Vacuoles ; Vasodilator Agents* ; Verapamil

PURPOSE: The purpose of this study was to evaluate the optimal diabetes duration for bone regeneration experiments in an alloxan monohydrate (ALX)–induced diabetic rabbit calvarial defect model by evaluating the association between diabetes duration and bone healing capacity. METHODS: Twenty-four New Zealand white rabbits were used. Twenty-two rabbits were injected with 100 mg/kg of ALX to induce experimental diabetes. These rabbits were divided into 4 groups, including a control group and groups with diabetes durations of 1 week (group 1), 2 weeks (group 2), and 4 weeks (group 3). Calvarial defects were created at 1, 2, and 4 weeks after ALX injection and in the control rabbits. Cone-beam computed tomography (CBCT) scanning was performed on the day of surgery and at 2 and 4 weeks after surgery. The rabbits were sacrificed 4 weeks after surgery, followed by histological and immunofluorescence analysis. RESULTS: The diabetic state of all diabetic rabbits was well-maintained throughout the experiment. Reconstructed 3-dimensional CBCT imaging showed more rapid and prominent bone regeneration in the control group than in the experimental groups. Histological staining showed notable bone regeneration in the control group, in contrast to scarce bone formation in the experimental groups. The appearance and immunoreactivity of receptor activator of nuclear factor-kappa B and osteoprotegerin did not show notable differences among the groups. CONCLUSION: ALX administration at 100 mg/kg successfully induced experimental diabetes in rabbits. The effect of diabetes on bone healing was evident when the interval between diabetes induction and the intervention was ≥1 week.
Alloxan ; Animals ; Bone Regeneration ; Cone-Beam Computed Tomography ; Diabetes Mellitus, Experimental ; Fluorescent Antibody Technique ; Osteogenesis ; Osteoprotegerin ; Rabbits ; Receptor Activator of Nuclear Factor-kappa B

OBJECTIVETo investigate the effect of ursolic acid (UA) on the alloxan-induced kidney injury in diabetic mice and explored its possible mechanisms.

METHODSDiabetes mellitus was induced in male Kunming mice by an injection of alloxan (70 mg/kg, i.v.). After 72 hours, blood glucose levels were detected and mice with blood glucose levels over 13.9 mmol/L were considered as diabetic and selected for further experiment. Thirty mice were randomly divided into three groups: control, diabetic and diabetic + UA(35 mg/kg/d, i.g. continuously for 8 weeks). Blood glucose concentration, organ coefficient of kidney, blood urea nitrogen (BUN), creatinine (Cr) as well as renal tissue levels of superoxide dismutase (SOD), methane dicarboxylic aldehyde (MDA), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined. Pathology of the renal tissue was measured by hematoxylin-eosin staining.

RESULTSCompared to the control group, blood glucose, organ coefficient of kidney, BUN and Cr increased significantly. In addition, SOD activities was reduced markedly and levels of MDA and inflammatory factors (TNF-α, IL-6) increased significantly. Renal cells from model group rats showed atrophy and disordered after HE staining and infiltration of inflammatory cells also appeared in renal tissue of the model group. These changes were significantly attenuated in the diabetic group treated with UA.

CONCLUSIONUA can significantly relieve renal damage in mice with diabetic nephropathy induced by alloxan, which might be related to decreased blood glucose level, antioxidation effect and inhibiting the production of inflammatory factors such as TNF-α and IL-6.

Alloxan ; adverse effects ; Animals ; Antioxidants ; metabolism ; Blood Glucose ; Blood Urea Nitrogen ; Creatinine ; metabolism ; Diabetes Mellitus, Experimental ; physiopathology ; Diabetic Nephropathies ; chemically induced ; drug therapy ; Interleukin-6 ; metabolism ; Kidney ; physiopathology ; Male ; Mice ; Superoxide Dismutase ; metabolism ; Triterpenes ; pharmacology ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo explore the role of insulin-like growth factor 1 (IGF-1) gene expression abnormality in neurotrophic causes of diabetic peripheral neurophathy.

METHODSDiabetes was induced in Sprague Dawley rats by alloxan. The parameters were measured as follows: IGF-1 mRNA by revere transcriptase-polymer chain reaction (RT-PCR); IGF-1 peptide by enzyme-linked immunosorbent assay (ELISA); electrophysiological parameters of nerves by evoked electromyogram; morphometric evaluation of sciatic nerves under light microscope and transmission electron microscope.

RESULTSDuring early diabetic stage, IGF-1 mRNA [(0.430+/-0.031) vs. (0.370+/-0.016), P<0.01, (0.430+/-0.031) vs. (0.280+/-0.010), P<0.001, respectively], IGF-1 peptide contents [(38.44+/-3.60) ng/mg vs. (30.06+/-2.41) ng/mg, P<0.01, (38.44+/-3.6) ng/mg vs. (3.71+/-2.70) ng/mg P<0.001, respectively] in sciatic nerve tissue reduced in diabetic rats with hyperglycemia and varied with severity of state when compared with non-diabetic control rats, and further gradually down-regulated in the diabetic rats with duration of diabetes [IGF-1 mRNA (0.320+/-0.021) to approximately (0.230+/-0.060); IGF-1 peptide (28.80+/-3.30) to approximately (19.51+/-1.80) ng/mg]. Furthermore, they correlated with nerve functional (sensory nerve conduction velocity: r=0.741, P<0.001; amplitude of evoked potential: r=0.716, P<0.001, respectively) and structural abnormality (axonal area r=0.81, P<0.001) of sciatic nerve. No difference was found in the above parameters between diabetic rats with euglycemia and non-diabetic control group.

CONCLUSIONIGF-1 gene expression in tissues was down-regulated from early diabetic stage, and varied with the severity and duration of diabetic state. The decrement in IGF-1 level might contribute to the initiation and development of diabetic neuropathy via autocrine or paracrine pathway.

Alloxan ; Animals ; Diabetes Mellitus, Experimental ; etiology ; metabolism ; Diabetic Neuropathies ; etiology ; metabolism ; Electrophysiology ; Evoked Potentials ; Insulin-Like Growth Factor I ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; physiopathology