Changes In Diabetic Rats Research Articles

Imbalance of glomerular VEGF-NO axis in diabetic rats: prevention by chronic therapy with propyl gallate

The uncoupling of the vascular endothelial growth factor-nitric oxide (VEGF-NO) axis may play a vital role in inducing glomerular endothelial dysfunction. We investigate the factors that contribute to the imbalance of the VEGF-NO axis and evaluate the effect of propyl gallate on preventing endothelial dysfunction. Streptozotocin (STZ, 60 mg/kg) was administrated to rats to establish an animal diabetic nephropathy model. The diabetic rats were randomly divided into a diabetic model group and a propyl gallate-treated group. Animals were sacrificed 8 weeks after the model was established. Periodic acid-Schiff staining was conducted to observe pathological changes, and reverse transcriptase polymerase chain reaction and Western blot were employed to analyze endothelial nitric oxide synthase (eNOS) and VEGF expressions. Commercial kits were used to detect glomerular eNOS activity and NO production, as well as oxidative stress. Compared with that in the normal control group, glomerular eNOS activity significantly decreased in diabetic rats, but eNOS expression remained at the same level. The expression of VEGF increased at this stage. Levels of glomerular oxidative stress also increased in diabetic rats and were inversely correlated with eNOS activity. Treatment with propyl gallate restored eNOS activity, ameliorated oxidative stress and improved glomerular pathological changes, but did not alter eNOS and VEGF expressions. The imbalance of the VEGF-NO axis in the glomeruli of diabetic rats may have resulted from eNOS inactivation, but not from the decrement in eNOS expressions at the early stage of rat diabetic nephropathy. Propyl gallate improved glomerular pathological changes in diabetic rats, possibly through oxidative stress reduction and VEGF-NO axis recovery.

Pancreas Transplantation Prevents Morphologic and Ultrastructural Changes in Pulmonary Parenchyma of Alloxan-Induced Diabetic Rats

Purpose The aim of this study was to evaluate whether pancreas transplantation (PT) is a suitable method for controlling histopathologic changes in lungs of alloxan-induced diabetic rats. Methods Sixty inbred male Lewis rats were randomly assigned to 3 experimental groups: NC, 20 nondiabetic control rats; DC, 20 untreated diabetic control rats; and PT, 20 diabetic rats that received syngeneic PT from normal donor Lewis rats. Each group was further divided into 2 subgroups of 10 rats each, which were killed after 4 and 12 weeks of follow-up. Clinical and laboratory parameters, fresh and fixed lung weights, and fixed lung volumes were recorded for all rats. Total number of alveoli, alveolar perimeter, alveolar surface area, and alveolar epithelial (AE) and endothelial capillary (EC) basal laminae thickening were randomly measured in 5 rats from each subgroup by using an image analyzer. For light microscopy, 250 alveoli were analyzed in each subgroup. For electron microscopy, 50 electron micrographs were examined for each subgroup. Results The DC rats showed elevated blood glucose and glycosylated hemoglobin levels, with insulin blood levels significantly lower than the NC rats ( P < .001). Fresh and fixed lung weights and fixed volumes were significantly reduced in these rats, although their proportions to body weight were increased at 12 weeks ( P < .01). The total number of alveoli in diabetic rats was higher than in control rats, whereas alveolar perimeter and surface area were significantly diminished ( P < .01). AE and EC basal laminae were significantly thicker in DC than in NC ( P < .01). Successful PT corrected all clinical and metabolic changes in diabetic rats, with sustained normoglycemia throughout the study. Morphologic and morphometric changes observed in diabetic lungs were completely prevented in PT rats from 4 weeks after transplant. Conclusion We conclude that PT can control morphologic and ultrastructural changes in pulmonary parenchyma, suggesting a promising perspective for preventing other chronic diabetic lesions.

Protective Effects of Grape Seed Proanthocyanidin Extracts on Cerebral Cortex of Streptozotocin-Induced Diabetic Rats through Modulating AGEs/RAGE/NF-κB Pathway

Diabetic encephalopathy is a severe complication in patients with long-term hyperglycemia. Oxidative stress is thought to be closely implicated in this disorder, so in this study, we examined whether grape seed proanthocyanidin extract (GSPE), a naturally occurring antioxidant derived from grape seeds, could reduce the injuries in the cerebral cortex of diabetic rats by modulating advanced glycation end products (AGEs)/the receptor for AGEs (RAGE)/nuclear factor-kappa B p65 (NF-kappaB p65) pathway, which is crucial in oxidative stress. Body weight and serum AGEs were tested; cerebral cortexes were isolated for morphological observations and the pyramidal cell layers were immunohistochemically stained for the detection of RAGE, NF-kappaB p65, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) as well. For RAGE and NF-kappaB p65, quantitative reverse transcriptase coupled to polymerase chain reaction (RT-PCR) was employed for determination of mRNA levels, and western blot was used to detect protein expression. Our results showed that long term hyperglycemia in diabetic rats caused the degeneration of neurons and the up-regulation of serum AGEs, and also the up-regulation of RAGE, NF-kappaB p65, VCAM-1 and ICAM-1 in the brain. We found that GSPE treatment improved the pathological changes of diabetic rats by modulating the AGEs/RAGE/NF-kappaB p65 pathway. This study enables us to further understand the key role that the AGEs/RAGE/NF-kappaB pathway plays in the pathogenesis of diabetic encephalopathy, and confirms that GSPE might be a therapeutical means to the prevention and treatment of this disorder.

Ultrastructural Investigation of the Retinal Changes in Diabetic Rat (OLETF)

Purpose: To compare retinal ultra-structures of diabetic rats (OLETF, Otsuka Long-Evans Tokushima Fatty) with those of agematched non-diabetic rats (LETO, Long-Evans Tokushima Otsuka) using transmission electron micrography (TEM). Methods: The body weights and blood sugar levels of the OLETF rats and LETO rats (n=5) were measured at 10 and 50 weeks of age. Using a TEM, we compared the ultra-structural changes between the retinas of the 50-week-old OLETF and LETO rats. We analyzed the sizes of the pericytes and the thicknesses of the retinal capillary basement membranes between the two groups. Comparisons were made using a Scion Image. Results: The mean body weight and blood sugar levels of the 50-week-old OLETF rats were significantly higher than those of the LETO rats (p

TSP-1 expression changes in diabetic rats with spinal cord injury

Objectives: Spinal cord injury (SCI) is associated with high morbidity and mortality worldwide, especially in patients with diabetes mellitus. Thrombospondin 1 (TSP-1) is a mutual activator and can cause neuron injury during hyperglycemia. We investigated the role of TSP-1 in a model of diabetic rats in the development of SCI.Methods: Thirty Sprague–Dawley female rats were divided into three groups (SCI group, SCI + diabetes group and sham-operated group) at random. Ten rats were intraperitoneally injected with streptozocin (60 mg/kg) to induce diabetes; the remaining 20 rats received an injection of 0.9% saline as SCI group and the third group was sham-operated group. Four weeks later, ten rats in the SCI group and ten diabetic rats were subjected to SCI using an impactor, and the sham-operated group was also followed at the same time course without SCI. These animals were killed at 12 hours after SCI for immunochemistry and Western blot analysis of the injured section for the expression of TSP-1 protein. Morphological changes of spinal cord in three groups also were observed through hematoxylin–eosin staining. All data were analysed by t-test.Results: The data of weight and blood sugar indicated no significant difference in all three groups before animal model induction. Four weeks after the induction of diabetes, the differences between the SCI and SCI + diabetes groups in weight and blood sugar were distinct. Immunochemistry and Western blot analysis showed increased TSP-1 expression in SCI group when compared with the sham-operated group rat but less than the SCI + diabetes group (p<0.01). The pathological alterations, such as central core lesion with a spare peripheral rim of tissue, and variable cyst formations and gliosis were very apparent in the damaged spinal cord area in the SCI group and especially in the SCI + diabetes group.Discussion: Our work provides experimental evidence that the elevated expression of TSP-1 can be detected in the injured segment of the spinal cord at 12 hours after injury in diabetic rats. It may contribute to severe damage in diabetic rats after SCI.

Histological assessment of the possible protective role of glimepiride against progression of experimentally induced diabetic nephropathy in rats

Introduction: little is known about the potential effects induced by sulphonylureas independently of their anti-hyperglycemic action. The present study examined the effect of glimepiride treatment on the progression of renal histological changes in diabetic rats to determine whether therapeutic intervention with these agents would prevent the onset and progression of renal complications or not. Material and methods: forty-eight adult male albino rats were equally divided into four groups; control, normal rats receiving glimepiride, streptozotocin induced diabetic non-treated rats and glimepiride-treated diabetic rats. Blood glucose level measurement and histological evaluation of renal tissue elements using H&E, Masson trichrome, and PAS reaction techniques at four and eight weeks after treatment were performed. Stained sections were subjected to some morphometric measurements namely, glomerular tuft area (GTA), mesangial matrix index (MMI) and area per cent of connective tissue (CT). Statistical analysis for significance of obtained data was performed using analysis of variance and student-T test. Results: Glimepiride did not cause any histological renal impairment when used solely. Induction of diabetes had a significant negative impact on renal structure. In addition to significant elevation of blood glucose levels, increased kidney and kidney to body weight ratio was estimated. A variety of histological changes affecting the glomerular and tubular elements of renal tissue were detected and were more intense in the eighth week of the experiment. A significant increase in GTA, MMI and area per cent of C.T. were also found in diabetic rats. All the tested parameters showed a significant improvement in the glimepiride-treated group. Conclusion: glimepiride could attenuate most of the histological changes produced in case of experimentally induced diabetic nephropathy in spite of persistent hyperglycemia. Recommendation: glimepiride could be used in Type I and type II diabetics to protect or slow down the progression of diabetic nephropathy.

Histological assessment of the possible protective role of glimepiride against progression of experimentally induced diabetic nephropathy in rats

Introduction: little is known about the potential effects induced by sulphonylureas independently of their anti-hyperglycemic action. The present study examined the effect of glimepiride treatment on the progression of renal histological changes in diabetic rats to determine whether therapeutic intervention with these agents would prevent the onset and progression of renal complications or not. Material and methods: forty-eight adult male albino rats were equally divided into four groups; control, normal rats receiving glimepiride, streptozotocin induced diabetic non-treated rats and glimepiride-treated diabetic rats. Blood glucose level measurement and histological evaluation of renal tissue elements using H&E, Masson trichrome, and PAS reaction techniques at four and eight weeks after treatment were performed. Stained sections were subjected to some morphometric measurements namely, glomerular tuft area (GTA), mesangial matrix index (MMI) and area per cent of connective tissue (CT). Statistical analysis for significance of obtained data was performed using analysis of variance and student-T test. Results: Glimepiride did not cause any histological renal impairment when used solely. Induction of diabetes had a significant negative impact on renal structure. In addition to significant elevation of blood glucose levels, increased kidney and kidney to body weight ratio was estimated. A variety of histological changes affecting the glomerular and tubular elements of renal tissue were detected and were more intense in the eighth week of the experiment. A significant increase in GTA, MMI and area per cent of C.T. were also found in diabetic rats. All the tested parameters showed a significant improvement in the glimepiride-treated group. Conclusion: glimepiride could attenuate most of the histological changes produced in case of experimentally induced diabetic nephropathy in spite of persistent hyperglycemia. Recommendation: glimepiride could be used in Type I and type II diabetics to protect or slow down the progression of diabetic nephropathy.

Zinc supplementation partially prevents renal pathological changes in diabetic rats

We have demonstrated that Zn supplementation mediated up-regulation of cardiac metallothionein (MT) as a potent antioxidant prevented the development of diabetic cardiomyopathy. The present study was undertaken to test whether induction of renal MT synthesis by Zn supplementation protects the kidney from diabetes-induced damage. Streptozotocin-induced diabetic rats were treated with and without Zn supplementation at 5 mg/kg in drinking water for 3 months. Diabetic renal damage was detected by examining renal pathological alterations and 24-h urinary protein levels. Three-month Zn supplementation immediately after the onset of diabetes, partially but significantly, prevented the kidney from diabetes-induced increases in 24-h urinary proteins and pathological alterations. Diabetes-induced renal oxidative damage, inflammation and up-regulated expression of profibrosis mediator connective tissue growth factor (CTGF) were also markedly attenuated by Zn supplementation, along with significant increases in Zn levels concomitant with MT expression in renal tubular cells. Direct exposure of renal tubular (HK11) cells to high levels of glucose (HG) induced CTGF up-regulation predominantly through ERK (extracellular signal-regulated kinase)1/2-dependent, and partially through p38 mitogen-activated protein kinase (MAPK)-dependent pathways. Pretreatment of HK11 cells with Zn or cadmium induced MT expression and also significantly suppressed HG-induced CTGF expression. These results provide the first evidence for Zn supplementation to attenuate diabetes-induced renal pathological changes, likely through prevention of hyperglycemia-induced CTGF expression by Zn-induced MT in renal tubular cells.

Early blood pressure-independent cardiac changes in diabetic rats

Cardiac remodeling is a key event in both diabetic and hypertensive heart diseases. In the present study, we investigated early myocardial changes in an animal model, the male Sabra rat model (SBH/y) of salt-induced hypertension-rendered diabetic with streptozotocin. Control non-diabetic (C), diabetic (D), and D or C rats made hypertensive by salt loading (DS or CS) were studied after 6 weeks. M-mode echocardiography revealed that left ventricular internal dimension during diastole and systole were significantly increased in D and DS, but not in C or CS. Concurrently, we found in D and DS an increase in cardiac beta-myosin heavy chain, atrial natriuretic peptide, skeletal alpha-actin mRNA, type III collagen, and transforming growth factor-beta. Myocardial angiotensin-converting enzyme (ACE) mRNA levels were increased while ACE2 mRNA levels were decreased in both D and DS groups. Cardiac angiotensin-1 (AT1) receptor protein levels were unchanged but the levels of phosphorylated (p) ERK and Jun-NH(2)-protein kinase (JNK) were increased in D and DS. In conclusion, we detected early cardiac changes in diabetic rats that were unrelated to hypertension. The increase in ACE, the decrease in ACE2, and the increase in cardiac pERK and pJNK suggest an increase in free angiotensin II and AT1R signaling in the diabetic myocardium as a possible mechanism contributing to cardiac remodeling in diabetes.

EFFECTS OF SELECTIVE INOS INHIBITION ON SYSTEMIC HEMODYNAMICS AND MORTALITY RATE ON ENDOTOXIC SHOCK IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

The purpose of this study was to examine whether selective iNOS inhibition can restore the hemodynamic changes and reduce the nitrotyrosine levels in the cerebral cortex of rats with streptozotocin-induced diabetes during endotoxin-induced shock. The study was designed to include three sets of experiments: (1) measurement of changes in systemic hemodynamics, (2) measurement of biochemical variables, including iNOS activity and nitrotyrosine formation in the brain, and (3) assessment of mortality rate. Rats were randomly divided into four groups: group 1, control; group 2, LPS: Escherichia coli endotoxin, 10.0 mg/kg (i.v.) bolus; group 3 (i.v.) LPS and L-N6-(1-iminoethyl)-lysine (L-NIL), 4mg/kg (i.p.); and group 4, LPS and NG-nitro-L-arginine methyl ester (L-NAME), 5 mg/kg (i.p.). In nondiabetic rats, administration of L-NIL prevented the hemodynamic and biochemical changes, and increases in plasma nitrite and cerebral nitrotyrosine levels induced by LPS. Administration of L-NAME partially prevented these LPS-induced changes. On the other hand, in diabetic rats, administration of L-NIL only partially prevented the hemodynamic and biochemical changes, and increases in plasma nitrite and cerebral nitrotyrosine levels associated with LPS. Administration of L-NAME, however, had no effects on these LPS-induced changes in diabetic rats. There was a significant difference in nitrotyrosine levels between nondiabetic and diabetic rats in groups 2, 3, and 4 at 2 and 3 h after the treatment (at 3 h; nondiabetic--control, 4.6 +/- 0.4; LPS (i.v.), 8.9 +/- 1.0, LPS (i.v.) + L-NIL, 4.7 +/- 0.5; LPS (i.v.) + L-NAME, 7.1 +/- 0.9; diabetic--control, 5.5 +/- 0.4; LPS (i.v.), 13.6 +/- 1.2; LPS (i.v.) + L-NIL, 9.0 +/- 0.9; LPS (i.v.) + L-NAME, 13.0 +/- 1.0; densitometric units). Insulin therapy resulted in a decrease in iNOS activity (at 3 h: 1.0 +/- 0.5 fmol mg min), nitrotyrosine formation (at 3 h; 5.0 +/- 0.5, densitometric units), and mortality rates (30% at 6 h, 50% at 12 h) in the LPS (i.v.) + L-NIL group of diabetic rats. Selective iNOS inhibition in diabetic rats could not improve hemodynamic instability, chemical changes, iNOS activity, and nitrotyrosine formation during septic shock compared with the improvements observed in nondiabetic rats. Tight glucose control along with administration of L-NIL can result in more effective restoration of the biochemical changes of septicemia in diabetic rats. Thus, hyperglycemia may be one of the mechanisms related to the aggravation of endotoxin-induced shock.

Protective effect of Liuwei Dihuang decoction on early diabetic nephropathy induced by streptozotocin via modulating ET-ROS axis and matrix metalloproteinase activity in rats RETRACTED ARTICLE

We aimed to investigate the effects of Liuwei Dihuang decoction (LW) on the endothelin-1-reactive oxidative species (ET-ROS) system and matrix metalloproteinases (MMPs) in the early diabetic nephropathy induced by streptozotocin (STZ) in rats. Rats were divided into six groups as follows: the control group, the untreated model group, the treated groups with the LW (5, 10 and 15 g kg(-1), p.o.) and the aminoguanidine-treated group (100 mg kg(-1), orally). The treatment was performed for 4 weeks, beginning on the fifth week after one intraperitoneal injection of STZ (65 mg kg(-1)). In the untreated model group, increased blood glucose, decreased plasma insulin level and an impaired renal function were observed. There was an altered redox system shown by an increased malondialdehyde and decreased activity of glutathione peroxidase and superoxide dismutase in the renal cortex. An enhanced inducible nitric oxide synthetase, total nitric oxide synthase and constitutive nitric oxide synthase and a declined nitric oxide were found. An increased extracellular matrix was indicated by an abnormality of MMP-2 and MMP-9 activities and an increase in hydroxyproline. An up-regulated ET-1 level and increased mRNA expression of endothelin-converting enzyme, preproET-1 and ET( A) receptor were presented in the affected renal cortex, but no change in ET(B) receptor mRNA. The LW was most effective in reversing these changes in diabetic rats and was as effective as aminoguanidine. The benefits of the extracts in relieving the abnormalities in early diabetic nephropathy are likely to be mediated by suppression of the renal ET-ROS system and escalating the activity of MMPs.

Effects of &lt;i&gt; Medicago sativa&lt;/i&gt; on nephropathy in diabetic rats

In this investigation, blood sugar and the kidney histopathological changes in diabetic rats were studied stereologically after being treated with the aqueous ethanol extract of Medicago sativa . Thirty two male Wistar rats were randomly divided into control, control+extract, diabetic and diabetic+extract groups (n=8). Diabetes was induced by intraperitoneal injection of 90 mg/kg of streptozotocin. Treatment with aqueous ethanol extract of Medicago sativa (550 mg/kg) was followed for 4 weeks. Then the left kidneys were excised and stereologically studied. The results revealed that blood sugar of the diabetic rats was reduced highly significant following treatment with aqueous ethanol extract of Medicago sativa . The final body weight in the diabetic, control and control+extract rats increased significantly in comparison with the first body weight but not in the diabetic+extract group. The kidney weight was the same in all groups except for the diabetic+extract rats which increased significantly compared to the control+extract ones. The total volume of kidney and the volume of cortex were the same in all groups while the volume of medulla increased significantly in the diabetic+extract groups compared to the control+extract ones. In addition the total glomerular volume increased significantly in diabetic rats compared to the control ones. In conclusion, although the consuming dose of the extract of Medicago sativa caused a noticeable reduction of blood sugar; however, it had no distinct effect on nephropathy side effects in this short term study.

C-Peptide Reverses Nociceptive Neuropathy in Type 1 Diabetes

We examined the therapeutic effects of C-peptide on established nociceptive neuropathy in type 1 diabetic BB/Wor rats. Nociceptive nerve function, unmyelinated sural nerve fiber and dorsal root ganglion (DRG) cell morphometry, nociceptive peptide content, and the expression of neurotrophic factors and their receptors were investigated. C-peptide was administered either as a continuous subcutaneous replacement dose via osmopumps or a replacement dose given once daily by subcutaneous injection. Diabetic rats were treated from 4 to 7 months of diabetes and were compared with control and untreated diabetic rats of 4- and 7-month duration. Osmopump delivery but not subcutaneous injection improved hyperalgesia and restored the diabetes-induced reduction of unmyelinated fiber number (P < 0.01) and mean axonal size (P < 0.05) in the sural nerve. High-affinity nerve growth factor (NGF) receptor (NGFR-TrkA) expression in DRGs was significantly reduced at 4 months (P < 0.01). Insulin receptor and IGF-I receptor (IGF-IR) expressions in DRGs and NGF content in sciatic nerve were significantly decreased in 7-month diabetic rats (P < 0.01, 0.05, and 0.005, respectively). Osmopump delivery prevented the decline of NGFR-TrkA, insulin receptor (P < 0.05), and IGF-IR (P < 0.005) expressions in DRGs and improved NGF content (P < 0.05) in sciatic nerve. However, subcutaneous injection had only marginal effects on morphometric and molecular changes in diabetic rats. We conclude that C-peptide exerts beneficial therapeutic effects on diabetic nociceptive neuropathy and that optimal effects require maintenance of physiological C-peptide concentrations for a major proportion of the day.

Effect of Vitamin E on diabetes-induced changes in small intestine and plasma antioxidant capacity in rat

The present study was designed to evaluate the effect of Vitamin E (Vit. E) on diabetes-induced changes in small intestine, lipid peroxidation and plasma antioxidant capacity in rats. Twenty-four rats were divided into three groups (n=8), namely control, non-treated diabetic (NTD) and Vit. E-treated diabetic (VETD) groups. The VETD group received 300 mg of Vit. E daily in drinking water. After 6 weeks, the length and weight of small intestine, villus height, crypt depth and muscular layer thickness showed a significant increase in the NTD group compared to the control group. In the VETD group, these parameters did not show any significant difference compared to the control group. The level of malondialdehyde (MDA) in the red blood cells showed a significant increase in the NTD group, but not in the VETD group, compared to the control group. The plasma antioxidant capacity showed a significant increase in VETD compared to the NTD group. These findings indicate that Vit. E significantly improved small intestinal changes in diabetic rats and that these effects could be mediated at least in part by enhanced plasma antioxidant capacity and reduced lipid peroxidation.

Real-time observation of glomerular hemodynamic changes in diabetic rats: Effects of insulin ARB

The progression of diabetic nephropathy is closely related to disturbances in glomerular hemodynamics, such as glomerular hypertension and/or hyperperfusion. The aim of this study was to observe and to analyze glomerular hemodynamics in rats with diabetes mellitus (DM) in vivo using confocal laser scan microscopy (CLSM). We also examined the effects of candesartan cilexetil (TCV-116), a selective angiotensin II type 1 receptor blocker (ARB), on glomerular hemodynamics in DM. Munich-Wistar rats were divided into six groups: (1) four-day control; (2) four-day DM; (3) 28-day control; (4) 28-day DM; (5) DM treated with insulin; (6) DM treated with TCV-116. The kidney-to-body weight ratio, glomerular volume, and proteinuria were estimated. Glomerular hemodynamic changes were observed using CLSM and renal expression of endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) was evaluated by immunofluorescence. The kidney-to-body weight ratio, glomerular volume, the diameters of afferent arterioles (AA) and efferent arterioles (EA), erythrocyte velocities within glomeruli, and volume flow in glomerular capillary loops in four-day DM were significantly higher than in control rats, and increases were even more pronounced in the 28-day DM. TCV-116 treatment ameliorated all these findings and significantly decreased proteinuria, but there was no effect on the blood glucose level. On the other hand, insulin treatment was followed by normalization of all these changes induced in DM. Enhanced renal expression of eNOS in DM was suppressed when treated with either TCV-116 or insulin, while expression of nNOS was unaltered among the four groups. This imaging procedure allowed us to evaluate glomerular microcirculation in vivo, including the diameters of AA and EA, erythrocyte velocity, and volume flow. DM significantly induced glomerular hemodynamic alteration and renal hypertrophy. DM treated with either insulin or ARB ameliorated these changes. This study shows that progress in imaging technology promises to make major contributions to revealing the involvement of hemodynamic changes in glomerular diseases, aiding prognosis and the monitoring of therapeutic effects, as well.

Trigonella foenum graecum seed powder protects against histopathological abnormalities in tissues of diabetic rats

Trigonella foenum graecum is a well-known hypoglycemic agent used in traditional Indian medicines. It was previously reported that oral administration of its seed powder for 3 weeks to alloxan diabetic rats stabilized glucose homeostasis and free radical metabolism in liver and kidney. In the present study, we further investigated the effects of 3 weeks alloxan induced diabetes on the histological structure and function of liver and kidney and the protective effect of T. foenum graecum seed powder (TSP) oral administration to the diabetic rats utilizing enzyme analysis and light and transmission electron microscopy. The activity of the enzyme, glutamate dehydrogenase was significantly higher whereas the activity of D-beta-hydroxybutyrate dehydrogenase enzyme was significantly lower in liver and kidney of alloxan-induced diabetic rats. Histopathological studies showed liver degenerative and early nephropathic changes in diabetic rats. Ultrastructure of the diabetic liver revealed a reduction in the rough endoplasmic reticulum and swelling of mitochondria in the hepatocytes. TSP treatment to the diabetic rats effectively prevented the alteration in the activities of the two enzymes and partially prevented the structural abnormalities thus suggesting a protective effect of TSP on the liver and kidney of the diabetic rats. The role of TSP in reversing the diabetic state at the cellular level besides the metabolic normalization further proves its potential as an antidiabetic agent.

Lower doses of vanadate in combination with trigonella restore altered carbohydrate metabolism and antioxidant status in alloxan-diabetic rats

Background: Vanadate treatment to diabetic rats has been reported to correct the altered carbohydrate metabolism and antioxidant status. However, vanadate exerts these effects at relatively high doses and several toxic effects are produced. We used low doses of vanadate in combination with Trigonella foenum graecum seed powder (TSP) and evaluated their effect on the enzyme changes in diabetic rats. Methods: Alloxan-diabetic rats were treated separately with insulin, vanadate (0.6 mg/ml), TSP and a combined dose of Vanadate (0.2 mg/ml) and TSP for 21 days. At the end of the experimental period, blood glucose levels and activities of pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) were measured in cytosolic fraction in the liver and kidney. Results: Blood glucose levels increased markedly in diabetic rats. Treatment with antidiabetic compounds resulted in the reduction of glucose levels. Rats treated with combined dose of vanadate and trigonella had glucose levels comparable to control ones. Similar results were obtained with the activities of PK, PEPCK, SOD, GPx, GR, and CAT in liver and kidney of diabetic rats. Combined dose of vanadate and Trigonella was found to be most effective in correcting these alterations. Conclusions: Lower doses of vanadate could be used in combination with TSP to effectively counter diabetic alterations without any toxic side effects.

The hepatic vagus mediates fat-induced inhibition of diabetic hyperphagia.

Diabetic rats both overeat high-carbohydrate diet and have altered hypothalamic neuropeptide Y (NPY) and corticotropin-releasing factor (CRF). In contrast, a high-fat diet reduces caloric intake of diabetics to normal, reflected by normal hypothalamic NPY and CRF content. How the brain senses these changes in diet is unknown. To date, no hormonal changes explain these diet-induced changes in caloric intake. We tested whether the common branch of the hepatic vagus mediates the fat signal. We presented fat in two ways. First, diabetic and vehicle-treated rats were offered a cup of lard in addition to their normal high-carbohydrate diet. Second, we switched diabetic rats from high-carbohydrate diet to high-fat diet, without choice. In streptozotocin-treated rats, both methods resulted in fat-induced inhibition of caloric intake and normalization of hypothalamic neuropeptides to nondiabetic levels. Strikingly, common branch hepatic vagotomy (unlike gastroduodenal vagotomy) entirely blocked these fat-induced changes. Although a shift in hepatic energy status did not explain the lard-induced changes in diabetic rats, the data suggested that common hepatic branch vagotomy does not interfere with hepatic energy status. Furthermore, common branch hepatic vagotomy without diabetes induced indexes of obesity. Abnormal function of the hepatic vagus, as occurs in diabetic neuropathy, may contribute to diabetic obesity.

Effect of combination therapy with a calcium channel blocker and an angiotensin-converting enzyme inhibitor on renal hypertrophy and urinary albumin excretion in diabetic rats.

The objective of this study was to compare the effect of an angiotensin-converting enzyme (ACE) inhibitor and a calcium channel blocker on the development of renal changes in diabetic rats. Diabetes was induced by an intravenous injection of streptozotocin in normotensive Wistar rats. Treatment was commenced immediately in 1 set of rats with 4 treatment arms: nitrendipine (250 mg/kg fodder), enalapril (35 mg/L drinking water), both treatments in combination, or placebo. Treatment was continued for 9 weeks. Another set of rats was left with untreated diabetes for 3 months followed by 7 weeks treatment as above. When starting treatment right after induction of diabetes, nitrendipine significantly reduced urinary albumin excretion (UAE) to the nondiabetic level (P < .05) without reducing blood pressure (BP), whereas enalapril failed to significantly reduce UAE despite a reduction in BP. Combining the two treatments showed no further reduction in UAE compared to monotherapy with nitrendipine, despite a lower BP. When leaving diabetic rats untreated for 3 months, only the coadministration of nitrendipine and enalapril showed a significant reduction in UAE compared to monotherapy and placebo treatment, but showed no significant effect on BP.

Echocardiographic texture analysis using the wavelet transform: differentiation of early heart muscle disease

Echocardiographic quantitation of myocardial texture for diagnosis of early cardiomyopathy (CMP) remains problematic. Conventional statistical methods are limited, contributed by a small image region-of-interest (ROI) and difficulty in discrimination from noise. This study was performed to evaluate the 2-D Haar wavelet decomposition method as a tool to identify textural changes in a rat model of early CMP, focusing on changes that occur before development of M-mode structural abnormalities. Early diabetic CMP, ethanol CMP and diabetic-ethanol CMP rat models were evaluated. Echocardiography was performed on two groups of rats. Group I (5 week cohort, n = 4 per subgroup) included controls, rats on 12% ethanol, a diabetic subgroup, and diabetic rats on 4% ethanol. Group II (10 week cohort, n = 5 per subgroup) included the same categories as group I with an additional subgroup taking 4% ethanol was also studied. M-mode left ventricular measurements were comparable in all subgroups of group I. However, diabetic rats in group II had an increased left ventricular dimension (LVD) compared to all others and an increased septal dimension (IVSD) and posterior wall dimension (PWD) were noted in the 4% and 12% ethanol groups. End-diastolic digital images of all rats in the parasternal short axis view, at the papillary muscle level, were downloaded to a computer. A 16 × 16 (ROI) was selected from the anterior interventricular septum. Although standard statistical methods could not differentiate any of the groups, calculation of textural energy and normalized textural energy with the 2-D Haar wavelet decomposition method found at 5 weeks increased normalized texture energy in diabetics compared to all others. At 10 weeks increased texture energy was noted in diabetics. Diabetic-ethanol rats at both 5 and 10 weeks revealed a blunted textural energy compared to diabetic rats. In a rat model of diabetic cardiomyopathy, the 2-D wavelet decomposition method identified textural energy changes before development of echocardiographic structural changes. Ethanol-associated blunting of textural changes in diabetic rats was also noted. This method for quantitation of ventricular texture may be relevant for diagnosis of early cardiomyopathy.