To determine the effect of the tumor necrosis factor-α (TNF-α) in odontoclast formation, we administrated a TNF-α inhibitor in rats with diabetes rats with periodontitis. The rats included in the study were divided into three groups: control rats without diabetes or periodontitis (the C group), rats with periodontitis and diabetes (the PD group), and rats with periodontitis and diabetes treated by infliximab, the TNF inhibitor (the PD+infliximab group). The PD and PD+ infliximab groups received intravenous administrations of streptozotocin (STZ, 50 mg/kg) to induce diabetes. After 7 days of STZ injections, the mandibular first molars were ligatured to induce periodontitis. The PD+infliximab group was intrapenitoneally administrated by infliximab (5 mg/kg). On days 3 and 20 after the ligature administration, odontoclast formation along root surfaces was evaluated by tartrate resistant acid phosphatase (TRAP) staining and cathepsin K immunohistochemistry. On day 3, the number of TRAP- and cathepsin K-positive cells increased more so in the PD group than in the C group. The PD+infliximab group showed a lower number of positive cells than the PD group. There was no difference in all the groups on day 20. On day 3, the cathepsin-K positive multinucleated and mononucleated cells were higher in the PD group than in the C group. The number of cathepsin-K positive multinucleated cells was lower in the PD+infliximab group than in the PD group. The PD group showed more cathepsin K-positive cells in the furcation and distal surfaces than the c group. The Cathepsin K-positive cells of the PD+infliximab group were lower than that of the PD group in furcation. These results suggest that TNF-α stimulates odontoclast formation in diabetes with periodontitis.
Acid Phosphatase ; Administration, Intravenous ; Animals ; Cathepsin K ; Cathepsins ; Immunohistochemistry ; Infliximab ; Ligation ; Molar ; Necrosis ; Osteoclasts* ; Periodontitis* ; Rats* ; Streptozocin

Mushrooms have become a largely untapped source of powerful new pharmaceutical products that poses anti-inflammatory, and antimutagenic, and antioxidant activities. The antioxidant effects of the mushroom may be partly explained by protecting cellular components against free radical. The aim of this study was to investigate the protective effect of chaga mushroom against diabetes, via the mitigation of oxidative stress and reduction of blood glucose, in streptozotocininduced diabetic rats. Rats were rendered diabetic by intravenous administration of STZ through tail at a dose of 50 mg/kg. Animals were allocated into four groups with 8 rats each. The control and diabetic control group were fed withstandard rat feed. The other diabeic groups, the low chaga extract group and the high chaga extract group were fed ad libitum using 0.5 g/kg and 5 g/kg of chaga mushroom extract, respectively, for 4 weeks. The blood glucose levels in the two chaga extract groups showed a tendency to decrease but did not reach statistical significance after the supplementation. Leukocyte DNA damage, expressed as tail length, was found to be significantly lower in the high chaga extract group than in the diabetic control group (p > 0.05). Plasma level of total radical-trapping antioxidant potential (TRAP) was tend to be higher in the high chaga extract group compared with the diabetic control group. Erythrocyte antioxidant enzyme activities of two groups did not differ. Although we did not obtain beneficial effect on lowering blood glucose levels in the STZ-induced diabetic rats, this results suggest that the chaga mushroom extracts may initially act on protecting endogenous DNA damage in the short-term experiment.
Administration, Intravenous ; Agaricales ; Animals ; Antioxidants ; Blood Glucose ; DNA ; DNA Damage ; Erythrocytes ; Leukocytes ; Oxidative Stress ; Pharmaceutical Preparations ; Plasma ; Rats ; Streptozocin ; Tail

OBJECTIVETo establish a blood glucose fluctuation model in diabetic rats.

METHODSMale SD rats were randomly divided into 2 groups, namely normal group and diabetes group. Rat model of diabetes was established by single intraperitoneal injection of streptozotocin (STZ) and then divided into sustained high blood glucose group and blood glucose fluctuation group. Rat model of blood glucose fluctuation was established by subcutaneous injection with regular insulin or gavaging of glucose twice daily in diabetic rats. The general condition, body weight, daily blood glucose levels of 5 different times, daily average blood glucose (MBG), standard deviation of daily average blood glucose (SDBG), the maximum amplitude of glycemic excursions (LAGE), fasting serum insulin (FINS) and pancreatic tissue pathology were observed.

RESULTSRats in blood glucose fluctuation group and sustained high blood glucose group developed symptoms of polyphagia, polyuria and polydipsia. Though significant differences in body weight were observed at different time (P<0.01), no significant differences were found among the three groups (P>0.05). After 6 weeks of blood glucose fluctuation, MBG, SDBG and LAGE in blood glucose fluctuation group and sustained high blood glucose group were increased significantly than those in normal group (P<0.01), the level of FINS decreased markedly (P<0.05). SDBG and LAGE in blood glucose fluctuation group were higher than those in sustained high blood glucose group (P<0.01). Islet of diabetic rat became atrophy, irregular shape, sparse distribution, and decreased in number, and the changes were more obvious in blood glucose fluctuation group.

CONCLUSIONRat model of blood glucose fluctuation can be successfully established by subcutaneous injection of regular insulin of gavage of glucose twice daily in diabetic rats.

Animals ; Blood Glucose ; analysis ; Body Weight ; Diabetes Mellitus, Experimental ; Fasting ; Glucose ; administration & dosage ; Insulin ; administration & dosage ; Male ; Rats ; Rats, Sprague-Dawley ; Streptozocin

The objective of this study was to investigate the hypoglycemic effects of quercetin (QE) in animal models of diabetes mellitus (DM). A starch solution (1 g/kg) with and without QE (100 mg/kg) or acarbose (40 mg/kg) was orally administered to streptozotocin (STZ)-induced diabetic rats after an overnight fast. Postprandial plasma glucose levels were measured and incremental areas under the response curve were calculated. To study the effects of chronic feeding of QE, five-week-old db/db mice were fed an AIN-93G diet, a diet containing QE at 0.08%, or a diet containing acarbose at 0.03% for 7 weeks after 1 week of adaptation. Plasma glucose and insulin, blood glycated hemoglobin, and maltase activity of the small intestine were measured. Oral administration of QE (100 mg/kg) or acarbose (40 mg/kg) to STZ-treated rats significantly decreased incremental plasma glucose levels 30-180 min after a single oral dose of starch and the area under the postprandial glucose response, compared with the control group. QE (0.08% of diet) or acarbose (0.03% of diet) offered to db/db mice significantly reduced both plasma glucose and blood glycated hemoglobin compared to controls without significant influence on plasma insulin. Small intestine maltase activities were significantly reduced by consumption of QE or acarbose. Thus, QE could be effective in controlling fasting and postprandial blood glucose levels in animal models of DM.
Acarbose ; Administration, Oral ; Animals ; Blood Glucose ; Diabetes Mellitus ; Diet ; Fasting ; Glucose ; Hemoglobins ; Hyperglycemia ; Hypoglycemic Agents ; Insulin ; Intestine, Small ; Mice ; Models, Animal ; Plasma ; Quercetin ; Rats ; Starch ; Streptozocin

The present study evaluated the effect of various dosages of soybean isoflavone extract on body weight changes, glucose tolerance and liver function in streptozotocin-induced diabetic rats. One group of normal rats (normal control) was fed an AIN-76-based experimental diet and four groups of diabetic rats were fed the same diet supplemented with four different levels of soybean isoflavone extract for seven weeks. The daily dosages of pure isoflavone for four diabetic groups were set to be 0 mg (diabetic control), 0.5 mg (ISO-I), 3.0 mg (ISO-II) and 30.0 mg (ISO-III) per kilogram of body weight, respectively. The daily consumption of isoflavone at the level of 3.0mg per kilogram of body weight resulted in the suppression of body weight loss and increased the survival rate of diabetic animals one and half times compared to that of the diabetic control group. Blood glucose levels in a fasting state and after the oral administration of glucose were significantly lower in the ISO-II group during the oral glucose tolerance test. The ISO-II group showed a tendency to elongate the gastrointestinal transit time. The activity of serum aminotransferases, indicator of liver function, was not negatively affected by any intake level of isoflavone. The present study demonstrated that the soybean isoflavone extract may be beneficial to diabetic animals by improving their glucose tolerance and suppressing weight loss without incurring hepatotoxicity at the daily dosage of 3.0 mg per kg of body weight.
Administration, Oral ; Animals ; Blood Glucose ; Body Weight ; Body Weight Changes ; Diet ; Fasting ; Gastrointestinal Transit ; Glucose Tolerance Test ; Glucose* ; Liver ; Rats* ; Soybeans* ; Streptozocin ; Survival Rate* ; Transaminases ; Weight Loss

OBJECTIVETo determine the optimal dosing of streptozotocin (STZ) for establishing lymphoma-bearing diabetic mouse models.

METHODSA total of 200 healthy male Balb/c mice were randomized into 4 groups (n=50) for intraperitoneal injection of a single dose of vehicle solution (control) or 75, 150, or 200 mg/kg STZ. The changes of body weight and blood glucose were observed regularly, and the success rate of modeling, mortality rate, and survival of the mice were recorded after the injections. The mice with successfully induced diabetes received subcutaneous or tail vein injection of A20 lymphoma cells, and the rate of tumorigenesis, mortality rate, and survival time were observed at 1 month and 3 months after tumor cell injection.

RESULTSCompared with the control group, the mice receiving STZ injection at 150 and 200 mg/kg showed significantly decreased body weight and increased blood glucose (P<0.05), while STZ at 75 mg/kg did not produced such obvious changes. STZ injection at 200 mg/kg resulted in a significantly higher mortality rate and shorter survival time than STZ at 150 mg/kg (P<0.05). In the control group and 150 and 200 mg/kg STZ groups, the rate of tumorigenesis or mortality rate showed no significant differences after subcutaneous injection of A20 lymphoma cells (P>0.05), but differed significantly at 3 months after tail vein injection of the tumor cells (P<0.05).

CONCLUSIONIntraperitoneal injection of STZ at 150 mg/kg is associated with a low mortality rate, a high successful modeling rate of diabetes and a long survival time in mice, and is therefore optimal for establishing diabetic mouse models bearing transplanted tumors.

Animals ; Blood Glucose ; Body Weight ; Diabetes Mellitus, Experimental ; Diabetes Mellitus, Type 2 ; chemically induced ; Injections ; Male ; Mice ; Mice, Inbred BALB C ; Streptozocin ; administration & dosage

Due to the multifactorial and multisystemic nature of diabetes mellitus, it is often treated with a combination of therapeutic agents having different mode of action. Earlier, we have synthesized several organozinc complexes and evaluated their safety and antidiabetic properties in experimental type 2 diabetes mellitus (T2DM). More recently, we have synthesized a metformin-3-hydroxyflavone complex and studied its antidiabetic efficacy in experimental rats. In the present study, a new zinc-mixed ligand (metformin-3-hydroxyflavone) was synthesized, characterized by spectral studies and its antidiabetic properties was evaluated in HFD fed—low dose streptozotocin induced T2DM in rats. The hypoglycemic efficacy of the complex was evaluated through oral glucose tolerance test, homeostasis model assessment of insulin resistance, quantitative insulin sensitivity check index and by determining the status of important biochemical parameters. Oral administration of the complex at a concentration of 10 mg/kg body weight/rat/day for 30 days significantly improved the glucose homeostasis. The complex possesses significant antidiabetic properties relatively at a less concentration than metformin-3-hydroxyflavone complex in ameliorating hyperglycemia.
Administration, Oral ; Animals ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Diet, High-Fat* ; Glucose ; Glucose Tolerance Test ; Homeostasis ; Hyperglycemia ; Hypoglycemic Agents ; Insulin Resistance ; Metformin ; Rats* ; Streptozocin* ; Zinc

The purpose of this study was to investigate the effect of butanol (BuOH) fraction of Alisma canaliculatum (Ac) and/or selenium (Se) treatment on glycogen level, lipid metabolism and lipid peroxidation in streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats were assigned to one of the five groups: normal, STZ-control, and three experimental groups (Ac group, Ac-Se group, and Se group). Diabetes was experimentally induced by intravenous administration of 45 mg/kg of STZ in citrate buffer. The BuOH fraction of Ac (400 mg/kg bw) was orally administered for 3 weeks. The Se group were fed a AIN-93 recommended diet mixed with Na(2)SeO(3) (2 mg/kg diet). The liver glycogen level of Ac and Ac-Se groups were significantly higher, when compared with the STZ-control groups. The muscle glycogen level was not significantly differ among all groups. The levels of liver triglyceride were higher in Ac-Se group than the STZ-control group. Pancreas protein levels were significantly increased in Ac-Se group than STZ-control group. The concentration of liver malondialdehyde (MDA) was significantly decreased in Ac and Se groups and decreased in Ac-Se group. Administration of BuOH fraction of Alisma canaliculatum and selenium supplementation increased the liver glycogen and triglyceride levels, and reduced peroxidative liver damage in STZ induced diabetic rats. These results suggest that treatment with a BuOH fraction of Alisma canaliculatum in combination with selenium has no synergistic antioxidative effect. Selenium supplementation may lead a decrease MDA of liver in diabetic rats.
Administration, Intravenous ; Alisma* ; Animals ; Citric Acid ; Diet ; Glycogen* ; Humans ; Lipid Metabolism* ; Lipid Peroxidation* ; Liver ; Liver Glycogen ; Male ; Malondialdehyde ; Pancreas ; Rats* ; Rats, Sprague-Dawley ; Selenium* ; Streptozocin ; Triglycerides

OBJECTIVETo discuss the effect of Zea mays L. saponin (ZMLS) on ultrastructure of kidney and pancreas in the diabetes rats induced by streptozocin.

METHODThe diabetic rat model was established by injections of STZ, blood glucose, the ultrastructure of the kidney and pancreas were observed.

RESULTCompared with the model group, the large, middle-dose ZMLS groups and melbinum group could remarkably decrease the blood glucose (P < 0.01), the large, middle, small-dose ZMLS groups could remarkably prevent the pancreatic islet beta-cell from the injury induced by Streptozotocin. Melbinum and the large, middle-dose ZMLS groups could remarkably increase mitochondrial Vv, deltam and euchromatin Vv (P < 0.01), and significantly decrease the delta, Nucleus delta and heterochromatin Vv (P < 0.01). The small dose of ZMLS obviously increases mitochondrial Vv (P < 0.05).

CONCLUSIONZMLS showed good effect on decreasing blood glucose and protection action on the kidney and pancreas injury of induced by STZ.

Animals ; Blood Glucose ; drug effects ; Diabetes Mellitus ; drug therapy ; Diabetes Mellitus, Experimental ; drug therapy ; Humans ; Kidney ; drug effects ; ultrastructure ; Male ; Pancreas ; drug effects ; ultrastructure ; Plant Extracts ; administration & dosage ; Rats ; Rats, Wistar ; Saponins ; administration & dosage ; Streptozocin ; Zea mays ; chemistry

OBJECTIVEAnabasis aretioides (Coss & Moq.), a Saharan plant belonging to Chenopodiaceae family, is widely distributed in semi-desert areas from the Tafilalet region of Morocco. This plant is extensively used by local population against diabetes and cardiovascular disorders. The purpose of the study was to investigate the effect of the aqueous A. aretioides extract on lipid metabolism in normal and streptozotocin (STZ)-induced diabetic rats and to identify the polyphenolic compounds present. In addition, the in vitro antioxidant activity of the aqueous A. aretioides extract was also evaluated.

METHODSThe effect of an aerial part aqueous extract (APAE) of A. aretioides (5 mg/kg of lyophilized A. aretioides APAE) on plasma lipid profile was investigated in normal and STZ-induced diabetic rats (n = 6) after once daily oral administration for 15 days. The aqueous extract was tested for its 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity. Polyphenolic compounds in the extracts were definitively characterized by high-performance liquid chromatography-diode array detection-electrospray ionization-mass spectrometry.

RESULTSIn diabetic rats, oral administration of A. aretioides APAE provoked a significant decrease in both plasma cholesterol and triglyceride levels from the first to the second week (P < 0.01). A significant decrease on plasma triglyceride levels was also observed in normal rats (P < 0.01), where the reduction was 53%. In addition, the phytochemical analysis revealed the presence of 12 polyphenolic compounds. Moreover, according to the DPPH radical-scavenging activity, the aqueous extract showed an in vitro antioxidant activity.

CONCLUSIONAqueous A. aretioides APAE exhibits lipid-lowering and in vitro antioxidant activities. Many polyphenols were present in this extract and these phytoconstituents may be involved in the pharmacological activity of this plant.

Animals ; Antioxidants ; administration & dosage ; Chenopodiaceae ; chemistry ; Cholesterol ; blood ; Chromatography, High Pressure Liquid ; Diabetes Mellitus, Experimental ; blood ; drug therapy ; Humans ; Hypolipidemic Agents ; administration & dosage ; chemistry ; Male ; Phytochemicals ; administration & dosage ; chemistry ; Plant Extracts ; administration & dosage ; chemistry ; Polyphenols ; administration & dosage ; chemistry ; Rats ; Rats, Wistar ; Streptozocin ; Tandem Mass Spectrometry ; Triglycerides ; blood