Dietary restriction prevents diabetogenic effect of streptozotocin in mice

The beneficial role of dietary restriction (DR) was studied in streptozotocin (STZ)-induced diabetes in mice. The DR mice exhibited the lower blood glucose (mg/dl) level as compared to ad libitum (AL) fed ones. After 3 months' DR, STZ treatment to both AL and DR mice showed significant (p < 0.001) elevation of the blood glucose level in AL-fed mice, while a lower level of glucose was maintained in DR-fed mice. The ability of maintaining a low blood glucose level in STZ-treated DR mice indicated that STZ might have been ineffective from its action on beta cells of pancreas by long-term DR. Thus, these findings suggested that DR may be an important tool for preventing the diabetic conditions. However, further studies are required to know the mechanism(s) of DR protection against diabetogenic action of STZ in experimental animals.     

Influence of nicotinamide administration on the bile-acid pattern in rats given streptozotocin

This study was carried out in order to exclude the possibility that streptozotocin (STZ) as such may be directly responsible for the alteration in the metabolism of bile acids. The STZ-diabetic rats had a higher percentage of cholic acid and a lower percentage of chenodeoxycholic acid and beta-muricholic acid compared to the controls. Although the rats were given STZ, yet there was no alteration in the bile acid pattern when they were protected against diabetes by simultaneous administration of nicotinamide. Nicotinamide itself had no influence on the composition of bile acids. Treatment of the STZ-diabetic rats with insulin cancelled the altered composition of bile acids partially. From these results it became clear that the alteration of the bile-acid metabolism in the STZ-treated rats was caused not by a direct effect of STZ itself but by an absolutely or relatively insulin-deficient state induced by STZ.     

Antihyperlipidemic effect of chlorogenic acid and tetrahydrocurcumin in rats subjected to diabetogenic agents

Diabetes mellitus is associated with dyslipidemia, which is a significant risk factor for cardiovascular complications. The present study was carried out to evaluate the effects of tetrahydrocurcumin (THC) and chlorogenic acid (CGA) alone and in combination on alterations in lipids, lipoproteins and enzymes involved in lipid metabolism in streptozotocin (STZ)–nicotinamide (NA)-induced type 2 diabetic rats. A significant (p < 0.05) increase in the concentrations of plasma and tissue (liver and kidney) lipids (cholesterol, triglycerides (TGs), free fatty acids (FFAs) and phospholipids (PLs)) and low density and very low-density lipoproteins (LDL and VLDL), and a decrease in the concentration of high-density lipoproteins (HDL) were noticed in STZ administered diabetic rats. In addition, the activity of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase increased significantly (p < 0.05) in the liver and kidney whereas the activities of lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) were decreased significantly (p < 0.05) in the plasma of diabetic rats. Combined administration of CGA (5 mg/kg b.w.) and THC (80 mg/kg b.w.) for 45 days remarkably reduced the STZ-induced changes in lipids, lipoproteins and lipid metabolising enzymes when compared to the effects of CGA or THC alone in diabetic rats. These results indicate that combination of THC and CGA can potentially ameliorate lipid abnormalities in experimental type 2 diabetes.     

Chronic administration of pioglitazone attenuates intracerebroventricular streptozotocin induced-memory impairment in rats

Memory impairment induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) in rats is associated with impaired brain glucose and energy metabolism, oxidative stress and impaired cholinergic neurotransmission. Treatment with antioxidants and cholinergic agonists has been reported to produce beneficial effect in this model. However, no reports are available on drugs that improve glucose utilization and metabolism. In the present study, we evaluated the effects of pioglitazone on cognitive performance, oxidative stress and glucose utilization in ICV STZ injected rats (3 mg/kg, on day 1 and 3). Pioglitazone (10 and 30 mg/kg) was administered per oral (p.o.) for 14 days, starting 5 days prior to STZ injection. Cognitive performance was assessed using step-through passive avoidance and Morris water maze task. Malondialdehyde (MDA) and glutathione levels in brain were estimated as parameters of oxidative stress. Glucose utilization by brain was assessed as the amount of glucose consumed from the media by the brain. ICV STZ injected rats showed a severe deficit in learning and memory associated with increased MDA levels (+67.5%), decreased glutathione levels (-29.2%) and impaired cerebral glucose utilization (-44.4%). In contrast pioglitazone treatment improved cognitive performance, lowered oxidative stress and improved cerebral glucose utilization in ICV STZ rats. The present study demonstrates the beneficial effects of pioglitazone in the ICV STZ induced cognitive deficits, which can be exploited for the dementia associated with diabetes and age-related neurodegenerative disorder, where oxidative stress and impaired glucose and energy metabolism are involved.     

Resistance of cats to the diabetogenic effect of alloxan

Experimental diabetes mellitus can be induced chemically in many species of animals with streptozotocin or alloxan. However, the cat is known to be resistant to the diabetogenic effect of streptozotocin. The purpose of this study was to find the optimal dose and rate of injection of alloxan to consistently produce hyperglycemia (blood sugar levels greater than 300 mg/dl) in cats. Alloxan was administered to 22 cats at various concentrations (50, 100 and 150 mg/kg) and different rates of injection (0.5, 1.0 and 1.5 ml/min). No hyperglycemic effect was observed at any of the concentrations or different rates of injection. Cats receiving high concentrations and/or high rates of injection of alloxan died due to kidney damage. The results of this study suggest that the cat is resistant to the diabetogenic effect of alloxan, but is susceptible to its toxic side effects.     

Characterisation of ventricular myocyte shortening after administration of streptozotocin (STZ) to neonatal rats

Human and animal studies have shown that diabetes mellitus can be associated with altered cardiac function that is independent of vascular complications. Streptozotocin (STZ) is a diabetogenic agent and when administered to rats causes selective beta-cell necrosis which is accompanied by a drastic reduction in plasma insulin and hyperglycaemia. We have investigated the characteristics of shortening in ventricular myocytes isolated from rat heart at 10 months after administration of STZ to neonatal rats at 2 days of age. The characteristics of shortening in myocytes from the STZ-treated neonatal rat compared to shortening in myocytes from the STZ-treated young adult rat are discussed. STZ-treated rats gained significantly less weight compared to age-matched controls. Although non-fasting blood glucose was not significantly different in STZ-treated rats they were found to be markedly glucose intolerant when given an intraperitoneal challenge of glucose (2 g/kg) after an overnight fast. During electrical stimulation (1 or 2 Hz) ventricular myocyte resting length, time to peak shortening, time to half relaxation and amplitude of shortening were not altered after STZ treatment. The imposition of rest periods (2-60 s) after trains of electrically stimulated (1 Hz) steady-state contractions resulted in a potentiation of the contraction, which immediately followed the rest period (post rest potentiation). Post rest potentiation was larger, following rest periods between 20 and 60 s, in myocytes from STZ-treated rats compared to controls. The absence of major alterations to the amplitude and kinetics of contraction in myocytes from STZ-treated neonatal rats at 10 months after treatment might be explained by a partial recovery of the beta-cells in the growing animal.     

Peripheral motilin administration stimulates feeding in fasted rats

Although the physiologic function of the gastrointestinal hormone motilin remains uncertain, plasma levels of this peptide vary with migrating myoelectric complexes (MMCs) in the small intestine. In the fed state, both MMCs and plasma motilin are suppressed. During fasting, cyclical peaks of motilin in plasma occur at the same time as Phase III of the MMC cycle occurs in the duodenum. This dependence of motilin concentrations in plasma on the feeding state of the animal prompted an investigation of the effects of motilin on feeding behavior. Intraperitoneal injection of motilin into fasted, but not fed, rats stimulated eating in a dose dependent manner. A significant stimulation of feeding was seen at doses of 5 and 10 μg/kg. Sated rats did not eat whether injected with motilin or vehicle. The feeding response to motilin was blocked by prior injection of the rats with naloxone, naltrexone, or pentagastrin. The dose response suppression of food intake by naloxone was similar in fasted animals treated with motilin or vehicle. Motilin may function as a hunger hormone during periods of fasting.     

Immunohistochemical changes of somatostatin cells in the pancreatic islets of rats after streptozotocin administration.

By the enzyme-labeled antibody method, cells containing somatostatin (SRIF) as well as insulin or glucagon were identified in pancreatic islets of the rat. SRIF antiserum was raised in rabbits followin immunization with synthetic SRIF coupled with human serum alpha-globulin and did not cross-react with hypothalamic, pituitary or gastrointestinal hormones using our immunoassay method. In the control rats, SRIF-containing cells were scattered in the periphery of the islets in close proximity to the outer glucagon containing cells. These latter cells were distributed in the outermost periphery of the islets. Insulin-containing cells were located in the central portion of the islets and dominantly occupied most of the islet. In the streptozotocin-diabetic rat, SRIF-containing cells were significantly increased in number whereas insulin-containing cells were markedly reduced. It is suggested from these findings that the number as well as the distribution of SRIF-, insulin- and glucagon-containing cells was important to the physiological and pathophysiological functioning of the islet.     

Protective effect of ganoderic acid against the streptozotocin induced diabetes,inflammation, hyperlipidemia and microbiota imbalance in diabetic rats

Diabetes mellitus (DM) is a metabolic disorder with numerous symptoms categorized via serves hyperglycemia effect along with altered fat, protein and carbohydrate metabolism mainly resultant from defects in insulin action/secretion or both. The aim of the current experimental study was to comfort the neuroprotective effect of ganoderic acid against the streptozotocin (STZ)-induced type I diabetes mellitus in mice and explore the underlying mechanism. Differentiation of 3T3-L1 preadipocytes effect; hepatic and glucose consumption effect of ganoderic acid was estimated on HepG2 cell lines and peroxisome proliferator-activated receptor (PPAR). FFA content was estimated in adipose and hepatic tissues. Ganoderic acid induced the 3T3-L1 preadipocytes differentiation. The mRNA expression of PPAR was increased in the high glucose-treated group in HepG2 and ganoderic acid treatment down-regulated the mRNA expression of PPAR. Ganoderic acid exhibited the inhibitory effect of α-glucosidase and α-amylase. Ganoderic acid demonstrated the reduced blood glucose and increase insulin level and also reduced the free fatty in hepatic and adipose tissue. Histopathological study showed the enhancement of β-cells in ganoderic acid-treated mice. Finally, their prebiotic effects on gut microbiota were illustrated via enhancing the population of diabetes resistant bacteria and also reducing the quantity of diabetes sensitive bacteria. Ganoderic acid attenuated STZ induced T1DM in mice via inflammatory pathways.     

Activity of receptor guanylyl cyclases in rats with neonatal streptozotocin diabetes and effect of intranasal administration of insulin and serotonin

In diabetes mellitus (DM) and its complications the functional activity of hormonal signaling systems and their sensitivity to the regulatory action of hormones are changed. We studied the activity of receptor forms of guanylyl cyclase (rGC) sensitive to natriuretic peptides ANP and CNP in the tissues of female rats with 240 day neonatal streptozotocin DM and the effects of intranasal administration of insulin and serotonin (6 weeks, daily dose for rat is 0.48 IU insulin or 20 μg serotonin). In diabetic rats, the increase of the basal rGC activity in the myocardium and its decrease in the uterus and ovaries were found, while in the brain, there were no differences from the control. The treatment of diabetic rats with insulin led to a decrease of the basal rGC activity in the myocardium and its restoration to a normal level in the ovaries. The administration of serotonin produced a less pronounced decrease in the basal enzyme activity in the myocardium compared to insulin and an insignificant increase in the brain. In the myocardium of diabetic rats, the guanylyl cyclase (GC)-stimulating effect of ANP was attenuated, whereas the CNP effect was enhanced; in the ovaries, the GC-stimulating effect of CNP and, to a lesser degree, the effect of ANP were decreased. In the uterus and brain of a diabetic rats, the rGC sensitivity to hormones was practically did not change. The administration of insulin to diabetic rats induces an increase of GC effect of ANP in the myocardium to its values in control and a decrease of CNP effect, as well as partially restored GC effect of CNP in the ovaries under the influence of CNP. The administration of serotonin somewhat enhanced effect of natriuretic peptides in the brain of both control and diabetic animals. Thus, in the neonatal model of type-2 DM in the myocardium and the tissues of the reproductive systems of rats, the functioning of natriuretic peptide-sensitive rGC is changed. The treatment of animals by insulin substantially restores rGC activity, while the intranasal serotonin administration has a little effect.     

Protection effect of cerium oxide nanoparticles against radiation-induced acute lung injuries in rats

IntroductionRadiation therapy is one of the most common tools for treating cancer. The aim is to deliver adequate doses of radiation to kill cancer cells and the most challenging part during this procedure is to protect normal cells from radiation. One strategy is to use a radioprotector to spare normal tissues from ionizing radiation effects. Researchers have pursued cerium oxide nanoparticles as a therapeutic agent, due to its diverse characteristics, which include antioxidant properties, making it a potential radioprotector.Materials and methodsOne hundred rats were divided into five groups of A) control group, intraperitoneal (IP) saline injection was done twice a week; B) bi-weekly IP injection of 14.5 nM (0.00001 mg/kg) CNP for two weeks; C) a single whole thorax radiation dose of 18 Gy; D) a single whole thorax radiation dose of 18 Gy + bi-weekly injection of 14.5 nM CNP for two weeks after radiation; E) bi-weekly IP injection of 14.5 nM CNP for two weeks prior to radiation + a single whole thorax radiation dose of 18 Gy. Thirty days after irradiation, 7 rats from each group were anesthetized and their lungs extracted for histopathological examination.ResultsStatistical analyses revealed that CNP significantly decreased the incidence of tissue collapse and neutrophile aggregation in rats receiving CNP before radiation in comparison with the radiation group.ConclusionThe results suggested the possibility of using CNP as a future radioprotector due to its ability to protect normal cells against radiation-induced damage.     

Effect of streptozotocin administration on somatostatin content of pancreas and hypothalamus in rats.

A radioimmunoassay (RIA) method for somatostatin (SRIF) utilizing rabbit antiserum against synthetic SRIF coupled with human serum alpha-globulin is described. Synthetic N alpha-tyrosylated SRIF was labelled with 125I using the lactoperoxidase method and purified on a Sephadex G-10 column. This assay system was highly specific for SRIF and did not cross-react with hypothalamic trophic hormones, pituitary trophic hormones or gastrointestinal hormones. The effect of streptozotocin induced diabetes on the SRIF content was examined in the pancreas, the pancreatic islets, as well as the hypothalamus of rats. SRIF content in both the pancreas and islets of the diabetic rats was shown by RIA to have significantly increased. However, content in the hypothalamus of the diabetic rats did not differ from that of the control. The physiological and pathophysiological significance of the SRIF changes remains to determined.     

Nephro-protective effect of granulocyte colony-stimulating factor in streptozotocin induced diabetic rats

Diabetic nephropathy is one of the most serious complications of diabetes and the major cause of end-stage renal failure. Consequences of diabetic nephropathy include increased kidney size and glomerular volume, thickening of basement membranes and progressive accumulation of extracellular matrix. Reports in the literature support an association between increased secretion of inflammatory molecules, such as cytokines, growth factors and metalloproteinases, and development of diabetic nephropathy. We investigated the potential of granulocyte colony- stimulating factor (G-CSF) as a therapeutic candidate for preventing diabetic nephropathy. We used 21 8-week-old male rats; 14 were administered a single dose of 60 mg/kg streptozotocin (STZ) to induce diabetes. The rats were divided into three groups of seven: group 1, control; group 2, diabetic; group 3, diabetic plus G-CSF treatment. After 4 weeks, immunoexpressions of transforming growth factor β1 (TGF-β1), Akt and CD34 levels were measured in the kidney tissue. Blood glucose, urine protein and the glomerular area also were measured for each group. We found that G-CSF treatment decreased TGF-β1 immunoexpression, urine protein and glomerular area in kidneys of diabetic rats, and increased CD 34 and Akt immunoexpression in kidneys of diabetic rats. The effects of G-CSF were independent of blood glucose levels. G-CSF may be a useful therapeutic agent for preventing diabetic nephropathy.