Attenuation of hyperglycemia and amadori products by aminoguanidine in alloxan-diabetic rabbits occurs via enhancement in antioxidant defenses and control of stress

The micro- and macro-complications in diabetes mellitus (DM) mainly arise from the damage induced by Amadori and advanced glycation end products, as well as the released free radicals. The primary goal of DM treatment is to reduce the risk of micro- and macro-complications. In this study, we looked at the efficacy of aminoguanidine (AG) to prevent the production of early glycation products in alloxan-diabetic rabbits. Type1 DM was induced in rabbits by a single intravenous injection of alloxan (90 mg/kg body weight). Another group of rabbits was pre-treated with AG (100 mg/kg body weight) prior to alloxan injection; this was followed by weekly treatment with 100 mg/kg of AG for eight weeks. Glucose, insulin, and early glycation products (HbA1C and fructosamine) were measured in control, diabetic and AG treated diabetic rabbits. The effects of hyperglycemia on superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx), reduced glutathione (rGSH), nitric oxide, lipid peroxides, and protein carbonyl were investigated. Alloxan-diabetic rabbits had lower levels of SOD, CAT, Gpx, and rGSH than control rabbits. Nitric oxide levels were considerably greater. AG administration restored the activities of SOD, CAT, Gpx enzymes up to 70–80% and ameliorated the nitric oxide production. HbA1c and fructosamine levels were considerably lower in AG-treated diabetic rabbits. The observed control of hyperglycemia and amadori adducts in alloxan-diabetic rabbits by AG may be attributed to decrease of stress and restoration of antioxidant defenses.

Investigation of Pomegranate Seed Oil Effects on the Renal Function in Alloxan-induced Diabetic Male Rabbits

Diabetes is a chronic disease which has reached pandemic proportions in a lot of countries of the world. In spite of the remarkable development in therapeutics chemistry, the usage of customary drugs is still a common practice for the treatment of diabetes. The current study was designed to investigate the effects of pomegranate seed oil (PSO) on kidney functions in the experimentally-induced diabetes in male rabbits. Diabetes was experimentally introduced by the intraperitoneal injection of alloxan monohydrate (150mg/kg BW). After three days of alloxan injection, samples were taken for the determination of glucose concentration. Serum glucose concentration of 200mg/ml was considered as an indication of animal diabetes. The experimental part was begun after 7 days of alloxan injection. Thirty two adult male rabbits were arbitrarily separated into four groups and treated daily for 45 days. Group 1 was kept with no treatment, group 2 included animals treated with 30mg/kg BW PSO, group 3 included diabetic animals that received alloxan with a dose of 150mg/kg BW, and, finally, group 4 included animals that received alloxan (150mg/kg BW) and treated with PSO (30mg/kg BW). Fasting blood samples were collected by heart puncture technique after 45days of experiments to assess glucose levels.

The effect of the experimental chronic hyperglycemia on the kidney and myocardium

The number of patients with diabetes increases annually. Modern forecasts predict that diabetes will be the seventh leading cause of death in 2030. Despite many significant advances in the research of diabetes and the use of new modern treatments, the disease is still progressing, and it is necessary to continue to study the effects of diabetes on human systems and organs: kidney and myocardium. Methods. A total of 24 rats of reproductive age (6 months old) were involved in this experimental study. Experimental rats were injected with alloxan intraperitoneally once at a dose of 20 mg/100 g on an empty stomach. In addition, they received a 10% glucose solution 24 hours after alloxan injection and a 5% glucose solution during the experiment. We measured glucose level with Accu-Chek Advantage (Boehringer, Germany) after 2, 12, and 24 hours after alloxan injection, and then weekly. The subjects of the investigation were kidney and heart of the experimental (n=12) and control (n=12) animals for correct comparative analysis. Results. The average blood glucose level remained at 11 mmol/L ± 2 mmol/L. During the experimental period, the rats' weight gain, dilation of both ventricles and relative renal weight gain were determined. By the histological examination of the myocardium, we revealed polymorphic nuclei, perinuclear cytolysis, fragmentation, wavy-like deformation of cardiomyocytes, stromal and perivascular edema, uneven filling of blood vessels, and local fibrosis. Thinning of fibrous capsule and cortical layer, destruction of nephrons, and hemorrhages were detected in the kidney. Conclusions. Our study confirms the robustness of alloxan-induced hyperglycemia in rats. We came to this conclusion because the early changes in the kidneys and heart are explained by the development of microangiopathies, which is a typical feature of the pathogenesis of diabetes. With prolonged exposure to chronic hyperglycemia, structural disorders of vital organs are worsened. This experimental model could be used for conducting comprehensive research aimed to study the mechanisms of diabetes mellitus, the effects of hyperglycemia on organs and tissues, and correct the complications.

The Potential of Neoagaro-Oligosaccharides as a Treatment of Type II Diabetes in Mice

Type 2 diabetes mellitus (T2DM) accounts for more than 90% of cases of diabetes mellitus, which is harmful to human health. Herein, neoagaro-oligosaccharides (NAOs) were prepared and their potential as a treatment of T2DM was evaluated in KunMing (KM) mice. Specifically, a T2DM mice model was established by the combination of a high-fat diet (HFD) and alloxan injection. Consequently, the mice were given different doses of NAOs (100, 200, or 400 mg/kg) and the differences among groups of mice were recorded. As a result of the NAOs treatment, the fasting blood glucose (FBG) was lowered and the glucose tolerance was improved as compared with the model group. As indicated by the immunohistochemistry assay, the NAOs treatment was able to ameliorate hepatic macrovesicular steatosis and hepatocyte swelling, while it also recovered the number of pancreatic β-cells. Additionally, NAOs administration benefited the antioxidative capacity in mice as evidenced by the upregulation of both glutathione peroxidase and superoxide dismutase activity and the significant reduction of the malondialdehyde concentration. Furthermore, NAOs, as presented by Western blotting, increased the expression of p-ERK1/2, p-JNK, NQO1, HO-1, and PPARγ, via the MAPK, Nrf2, and PPARγ signaling pathways, respectively. In conclusion, NAOs can be used to treat some complications caused by T2DM, and are beneficial in controlling the level of blood glucose and ameliorating the damage of the liver and pancreatic islands.

INFLUENCE OF PIRDOT LEAF (SAURAUIA VULCANI, KORTH.) EXTRACT ON THE BLOOD GLUCOSE RATE AND HISTOLOGIC DESCRIPTION OF THE RETINA OF MALE MICE (MUS MUSCULUS STRAIN DDW)

Objective: This research aims to collect laboratory data on the influence of pirdot leaf extract on the retina and blood glucose rate.Method: The mice were classified into 5 groups: A control group without any treatment, a control group treated with a single injection of 125 mg/kg body weight (BW) of alloxan as the diabetes mellitus trigger, and three groups treated with intra-muscular alloxan injection to induce diabetes mellitus, and pirdot leaf extract, i.e., 150 mg/kg BW (P1), 200 mg/kg BW (P2), and 250 mg/kg BW (P3) for 8 weeks. Subsequently, the blood glucose rates of the mice were measured, and histologic grazes of their retina layers were prepared using the paraffin method.Results: The blood glucose rate of the mice treated with 200 mg/kg BW (113.4 mg/dl) pirdot leaf extract significantly differed from that of the mice in the diabetes mellitus control group (364.8 mg/dl) (p<0.05). The ganglion cell layer of the retina increased by up to 7.59 μm, which differed from that of the diabetes mellitus group (3.67 μm) (p<0.05) treated with 250 mg/kg BW pirdot leaf extract. The external plexiform layer increased to 17.88 μm, which differed from that of the diabetes mellitus group (15.71 μm) (p<0.05) treated with 150 mg/kg BW pirdot leaf extract.Conclusion: The blood glucose rate obtained after treatment with pirdot leaf extract was lower than that of the diabetes mellitus control group.

Evaluation of antidiabetic potential of hydroalcoholic extract of Annona squamosa (HAEAS) leaf in alloxan monohydrate induced diabetic Albino rats

Background: Diabetes is almost growing health concern worldwide and now emerging as an epidemic world over. Recently, full attention is being paid to the study of natural products as potential antidiabetics. Objective of the study was to evaluate the antidiabetic effect of hydroalcoholic leaf extract of Annona squamosa (HAEAS) plant in alloxan monohydrate induced diabetic albino rats.Methods: Almost a 30 Albino rats with 150- 200 grams weight were weighed and grouped into 5 equal groups taking 6 rats in every group. Group A served as normal control, Group B as diabetic control, received alloxan monnohydrate. Group C and D was received alloxan + HAEAS suspension at 350 and 700 mg/kg doses orally respectively, Group E was given alloxan + standard drug (Glibenclamide 5mg/kg) suspension for 28 successive days and the effect of HAEAS on blood sugar(BS) levels was measured at regular intervals. At the end portion of this investigational research study samples of blood were collected from all rats on 0day (initial), after 72 hrs and after 28th day (29thday) of given test drug HAEAS treatment for biochemical estimation of BS and the BS values were observed.Results: The present research study revealed that HAEAS leaves has antidiabetic effect against alloxan monohydrate induced diabetic rats on i.p. alloxan injection at 150mg/kg.b.w. and confirms that on i.p. alloxan injection causes a significant rise off BS in untreated albino rats when compared to control group. Diabetic rats treatment with HAEAS leaves for 28 days caused dose a dependent fall in BS values. Glibenclamide treated diabetic rats also showed a significant (P <0.00) fall in BS content after 28 days of treatment.Conclusions: This research study confirms that HAEAS leaves has shown significant antidiabetic effect at 350 and 700 mg/kg. b.w. doses in alloxan monohydrate induced diabetic rats.

Liver and skeletal muscle ceramides in alloxan-induced diabetes

Aim. To study of liver and sceletal muscle ceramides in alloxan-induced diabetes at different periods after alloxan exposure. Methods. Repeated experiments were performed on white male rats. Diabetes was modeled by alloxan hydrochloride solution intraperitoneal injection. The disease development was monitored using clinical and laboratory parameters. Ceramides in tissues were determined in intact animals (control), at the 10, 20, 30, 45 and 60 day after the alloxan injection. Ceramides level in the plates was determined by thin layer chromatography using the external standard. Results. In intact animals, ceramides level in liver was twice as high as in muscle. At all terms after alloxan injection, ceramide level was significantly higher compared to controls, and was in muscle compared to liver, with similar change pattern. Up to the 20th day, a significant increase of ceramide level was observed compared to control (eightfold in liver and sevenfold in muscle). By 30th day, a partial recovery was registered, followed by subsequent increase of ceramide level. This indicates the influence of compensation mechanisms in the early stages of the experiment with further decompensation on late stages. Conclusion. In alloxan-induced type 1 diabetes, ceramide level in insulin-dependent tissues depends on the term after the alloxan injection; the findings are of great importance for the research of secondary insulin resistance, as well as other diabetes-associated pathological conditions, exact mechanisms.

Preventive Effects of Flavonoids on Alloxan-Induced Diabetes Mellitus in Rats

The aim of the present study was the evaluation of possible protective effects of quercetin and chrysin in experimental alloxan-induced diabetes in rats. Alloxan was injected at a single dose of 60 mg/kg (into the tail vein) for diabetes induction. Quercetin (50 and 100 mg/kg; orally) and chrysin (50 and 100 mg/kg; orally) were administered daily for 3 days prior and 7 days after alloxan injection. Alloxan induced a significant increase of glycaemia (p < 0.001) in comparison with control animals. Quercetin at both doses prevented serum glucose elevation (p < 0.001). However, the protective effect of chrysin was weaker and surprisingly, most prominent at the lower dose (p < 0.05; p < 0.01). On the other hand, glycosuria was increased in all groups of animals receiving alloxan. We suggest that the protective effect of the used flavonoids in experimental diabetes mellitus may be related to their antioxidative/chelatory properties. Increased glycosuria indicated that inhibition of renal glucose reabsorption may also play a role in the hypoglycaemic effect of both flavonoids.

The number of podocyte and slit diaphragm is decreased in experimental diabetic nephropathy

PURPOSE: To determine the number of podocyte, slit diaphragms, slit diaphragm extensions and GBM thickness in diabetic nephropathy. METHODS: Sixty "Rattus Wistar"of both sexes weighing 200-300g were divided in two experimental groups: normal group 10 animals, and alloxan diabetic rats - 50 animals. Alloxan was administered in a single IV dose of 42mg/kg body weight. Body weight, water and food intake, diuresis, and blood and urine glucose were determined in both groups before alloxan injection and two weeks, six and twelve months after alloxan injection. Proteinuria was measured at 12 months in both groups. After 12 months animals were sacrificed, and the right kidney processed for electron microscopy. RESULTS: Clear clinical and laboratory signs of severe diabetes were seen, in all alloxan-diabetic rats at all follow-up times. Glomerular basement membrane (GBM) thickening, podocyte number, and slit diaphragm number and extension were determined. GBM of all diabetic rats was significantly thicker (median=0.29µm; semi-interquartile range=0.065µm) than in the normal rats (0.23µm; 0.035µm). Diabetic rat podocyte number (8; 1), slit diaphragm number (4; 1), and slit diaphragm extension (0.021µm; 0.00435µm) were significantly lower than in normal rats (11; 1) and (7; 1.5), and (0.031µm; 0.0058µm). Diabetic rat proteinuria (0.060mg/24h; 0.037mg/24h) was higher than in normal rats (0.00185mg/24h; 0.00055mg/24h). CONCLUSION: Experimental diabetes is associated with significant (p<0.05) changes in podocyte foot process, slit number, slit diaphragm extension, and GBM thickness.