STZ-diabetic Rats (stz-diabetic + rat)

Distribution by Scientific Domains


Selected Abstracts


Occurrence of oxidative impairments, response of antioxidant defences and associated biochemical perturbations in male reproductive milieu in the Streptozotocin-diabetic rat

INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 6 2007
B. Shrilatha
Summary Oxidative stress is implicated to play a vital role in the pathogenesis of various diabetic complications. While reproductive dysfunction is a well recognized consequence of diabetes mellitus, the underlying mechanisms are poorly understood. The present study aims to obtain insights into the incidence, extent and progression of oxidative impairments in testis and epididymal sperm (ES) in streptozotocin (STZ)-induced diabetic rat during early and progressive phase. Adult rats (CFT-Wistar strain) rendered diabetic by an acute dose of STZ (60 mg/kg bw, i.p.) were examined for induction of hyperglycaemia at 72 h, followed by the assessment of oxidative impairments in testis and ES over a 6-week period. Oxidative damage was ascertained by measuring the malondialdehyde levels, reactive oxygen species (ROS) generation, alterations in antioxidant defences and extent of protein oxidation. STZ induced a significant (2.5-fold) increase in blood glucose levels. In diabetic rats, both testis and ES showed enhanced status of lipid peroxidation measured as increased TBARS and ROS from week 2 onwards. These impairments in testis were consistent, progressive and accompanied by marked alterations in antioxidant defences and elevated protein carbonyls. Varying degree of reduction in the specific activities of antioxidant enzymes was evident in testis and ES, while the activity of glutathione- S -transferase (GST) was significantly elevated. Reduced glutathione (GSH) and vitamin E levels were consistently reduced in testis. Lipid dysmetabolism measured in terms of increased cholesterol, triglycerides and phospholipids was evident only beyond week 2 in diabetic testis. Taken together, these results indicate that the testis and ES are indeed subjected to significant oxidative stress in the STZ-diabetic rat both during early as well as progressive phase. It is hypothesized that oxidative impairments in testis which develop over time may at least in part contribute towards the development of testicular dysfunction eventually leading to testicular degeneration which culminates in reduced fertility during the progressive phase of STZ-induced diabetes in adult rats. [source]


Insulin mimetic effects of macrocyclic binuclear oxovanadium complexes on streptozotocin-induced experimental diabetes in rats

DIABETES OBESITY & METABOLISM, Issue 6 2003
B. Ramachandran
Aim:, The vanadium complexes so far tested for their insulin mimetic effects are either mono- or binuclear and contain only acyclic ligands. The leaching or hydrolysis of vanadyl ions from these complexes is much easier, and hence they elicit side effects. In the present study, a new binuclear macrocyclic oxovanadium complex was synthesized, and its efficacy was studied on streptozotocin (STZ)-induced diabetic rats over a period of 30 days. Methods:, The insulin mimetic effect of the complex was tested on the blood sugar level in the STZ-diabetic rats and on the activities of the carbohydrate-metabolizing enzymes present in the liver. Results:, Administration of vanadium complex to STZ-induced diabetic rats decreased blood glucose levels from hyperglycaemic to normoglycaemic when compared to diabetic rats. The activity of carbohydrate-metabolizing enzymes such as hexokinase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen content were increased to near normal in vanadium complex-administered diabetic rats. The biochemical studies such as assay of blood urea and glutamate oxaloacetate transaminases revealed that the complex is not toxic to the system. Conclusion:, The nontoxic nature of this complex may be due to the presence of the vanadyl ions in an intact macrocyclic form. Further, the vanadyl ions present in the macrocyclic binuclear oxovanadium complex are very close to each other, and this may enhance the insulin mimetic activity by synergic effect. [source]


Effects of aminoguanidine and tolrestat on the development of ocular and renal structural changes in experimental diabetic rats

DIABETES OBESITY & METABOLISM, Issue 1 2002
Ö. Azal
Studies that researched the role of aminoguanidine and tolestat in the prevention of diabetic retinopathy and nephropathy resulted in conflicting data. We investigated the effects of these agents in the prevention of ocular and renal changes in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by intravenous injection of STZ in 30 rats. Ten rats that were not given STZ served as non-diabetic control (Group 1). Ten STZ-diabetic rats that were not given any treatment served as diabetic control (Group 2). Groups 3 and 4 were composed of STZ-induced diabetic rats (10 each) that were given tolrestat and aminoguanidine respectively. Eyes and kidneys were examined at the 24th week under electronmicroscopy. Cataract was observed in all six of the surviving rats in Groups 2 and 4, and in one of 6 surviving rats in group 3. Cataract development was lower in Group 3 than Groups 2 and 4. All retinal samples obtained from group 2 demonstrated a number of structural abnormalities, whereas there were no significant ultrastructural changes in groups 3 and 4. Groups 2 and 3 demonstrated mesangial proliferation and expansion, diffuse glomerular basement membrane (GBM) thickening, and focal GBM thickening in the bulb form. Group 4 demonstrated a normally appearing mesangial space, minimal diffuse but no focal GBM thickening. The urinary albumin excretion (UAE) was lower in Group 4 than the other groups. In conclusion, our results suggest that aminoguanidine may be an important agent for the prevention of renal changes, whereas tolrestat may be effective for the prevention of ocular changes in diabetes mellitus. [source]


Hypoglycaemic and hypolipidaemic effects of fractions from kolaviron, a biflavonoid complex from Garcinia Kola in streptozotocin-induced diabetes mellitus rats

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2006
O. A. Adaramoye
In the search for natural hypoglycaemic agents as alternatives to synthetic ones that are expensive and not easily accessible, and to justify the use of Garcinia kola seeds in traditional African medicine to treat diabetes, the hypoglycaemic and hypolipidaemic effects of fractions from kolaviron (KV) (a Garcinia kola seed extract) were investigated in normal and streptozotocin (STZ)-diabetic rats. KV, a biflavonoid complex from Garcinia kola seed, was separated by thin-layer chromatography into three fractions; Fraction I (FI), Fraction II (FII) and Fraction III (FIII) with RF values of 0.48, 0.71 and 0.76, respectively. In normoglycaemic rats, KV, FI and FII administered at a dose of 100 mg kg,1 body weight elicited significant (P < 0.05) hypoglycaemic activity within 4 h of oral administration. Precisely, KV, FI and FII decreased blood glucose levels of normoglycaemic rats by 66%, 50% and 61%, respectively, when compared with controls 30 min after oral administration of the extracts. In hyperglycaemic rats, KV, FI and FII significantly (P < 0.05) reduced blood sugar levels in STZ-diabetic rats within 4 h of oral administration. Furthermore, KV alone produced a significant (P < 0.05) anti-diabetic effect from day 3 to day 7 of oral intubation of STZ-diabetic rats. In addition, the extracts showed favourable effect on the plasma lipid profile of STZ-diabetic rats, and also decreased significantly (P < 0.05) the STZ-induced increase in the activity of microsomal glucose-6-phosphatase and lipid peroxidation (LPO) products. This study confirms the anti-diabetic and hypo-lipidaemic effects of KV in STZ-diabetic rats. These observed effects of KV are attributed to two of its fractions, FI and FII, with RF values of 0.48 and 0.71, respectively. [source]


Phrenic nerve diabetic neuropathy in rats: unmyelinated fibers morphometry

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2009
Valéria Paula S. Fazan
Abstract We have demonstrated that phrenic nerves' large myelinated fibers in streptozotocin (STZ)-induced diabetic rats show axonal atrophy, which is reversed by insulin treatment. However, studies on structural abnormalities of the small myelinated and the unmyelinated fibers in the STZ-model of neuropathy are limited. Also, structural changes in the endoneural vasculature are not clearly described in this model and require detailed study. We have undertaken morphometric studies of the phrenic nerve in insulin-treated and untreated STZ-diabetic rats and non-diabetic control animals over a 12-week period. The presence of neuropathy was assessed by means of transmission electron microscopy, and morphometry of the unmyelinated fibers was performed. The most striking finding was the morphological evidence of small myelinated fiber neuropathy due to the STZ injection, which was not protected or reversed by conventional insulin treatment. This neuropathy was clearly associated with severe damage of the endoneural vessels present on both STZ groups, besides the insulin treatment. The STZ-diabetes model is widely used to investigate experimental diabetic neuropathies, but few studies have performed a detailed assessment of either unmyelinated fibers or capillary morphology in this animal model. The present study adds useful information for further investigations on the ultrastructural basis of nerve function in diabetes. [source]


MACROPHAGE INFILTRATION AND INDUCTION OF P75 NTR AND IL-1B IN THE NERVE OF DIABETIC RATS

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2000
G. Conti
Recently, inflammation has been involved in the pathogenesis of diabetic neuropathy, and activated macrophages have been found in the peripheral nervous system of diabetic rats, with a possible role in chemotaxis and regeneration. In this study, we obtained sciatic nerve specimens from diabetic rats at different time points following STZ administration. Macrophages infiltration, IL-1b and p75NTR induction were analyzed by immunocytochemistry on frozen sections and on teased nerve fibers. Apoptosis was detected on teased nerve fibers by TUNEL and DAPI staining. Cell phenotype was characterized by double-staining with antibodies specific for Schwann cells and macrophages. The nerves obtained from STZ-diabetic rats showed macrophages infiltration by day 14 following STZ administration, with complete clearance by day 35. Fifteen percent of these cells were TUNEL positive. IL-1B induction was concomitant with macrophages infiltration and not detectable by day 35. p75NTR expression began by day 21, peaking by day 35, and dropping to barely detectable levels by day 105. These findings seem to indicate that the concomitance of these processes may be crucial in the regulation of nerve damage and in promoting an attempt of regeneration at the early stages of STZ diabetic neuropathy. [source]


Inhibition of calcium/calmodulin-dependent protein kinase II normalizes diabetes-induced abnormal vascular reactivity in the rat perfused mesenteric vascular bed

AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 1 2003
M. H. M. Yousif
Summary 1 Calcium/calmodulin-dependent protein kinase II (CaMKII) has an important function in mediating insulin release but its role in the development of diabetes-induced cardiovascular complications is not known. 2 We investigated the ability of a chronic administration of KN-93 (5 mg kg,1alt diem for 4 weeks), an inhibitor of CaMKII, to modulate the altered vasoreactivity of the perfused mesenteric bed to common vasoconstrictors and vasodilators in streptozotocin (STZ)-induced diabetes. 3 The vasoconstrictor responses induced by noradrenaline (NE), endothelin-1 (ET-1), and angiotensin II (Ang II), were significantly increased whereas, vasodilator responses to carbachol and histamine were significantly reduced in the perfused mesenteric bed of the STZ-diabetic rats as compared with non-diabetic controls. 4 Inhibition of CaMKII by KN-93 treatment did not affect blood glucose levels but produced a significant normalization of the altered agonist-induced vasoconstrictor and vasodilator responses. KN-93 did not affect agonist-induced responses in control animals. In addition, KN-93 significantly reduced weight loss in diabetic rats. 5 The present data suggest that CaMKII is an essential mediator in the development of diabetic vascular dysfunction and may also play an important role in signalling pathways leading to weight loss during diabetes. [source]


Role of protein kinases in mediating diabetes-induced augmented vasoconstriction to endothelin-1 in the renal arteries of STZ-diabetic rats

CELL BIOCHEMISTRY AND FUNCTION, Issue 5 2006
Mariam H. M. Yousif
Abstract Diabetes is associated with increased reactivity of the renal vascular bed to endothelin-1 (ET-1). It has been observed that diabetes is associated with over-expression of ETA - and ETB -receptors in the rat renal cortex. However it is not known if these receptors are over-expressed in the renal artery. The objectives of this study were to determine changes in ET-1 receptors and signalling pathways in diabetic renal arteries, to determine the relative roles of protein kinase C and tyrosine kinase activation in mediating these responses and to investigate the role of Rho-kinase activity in mediating the vasoconstrictor responses to ET-1. This study was performed on isolated renal artery segments obtained from STZ-diabetic rats. Results from this study showed that the vasoconstrictor response to ET-1 was potentiated in the diabetic renal artery segments compared to the control animals. Using selective ET-1 receptor antagonists, BQ123 and BQ788, the enhanced ET-1-induced vasoconstriction was shown in this study not to be related to changes in receptor affiinity or receptor subtype distribution. However, the augmented vasoconstrictor response to ET-1 in the diabetic renal artery preparations may be related to increased influx of Ca2+ through L-type channels and also to increased tyrosine kinase activity. Copyright © 2005 John Wiley & Sons, Ltd. [source]


Effects of Hilsa ilisa fish oil on the atherogenic lipid profile and glycaemic status of streptozotocin-treated type 1 diabetic rats

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2004
Ishtiaq Mahmud
Summary 1.,The effects of oral administration of Hilsa (Hilsa ilisa) fish oil (1 g oil/kg bodyweight per day) on the lipid profile, platelet aggregation, anti-oxidative status and glycaemic control of streptozotocin (STZ; 90 mg/kg bodyweight)-treated type 1 diabetic rats were compared with those in fish oil-treated or untreated non-diabetic rats. 2.,After 3 weeks of fish oil feeding, plasma total cholesterol decreased in both the non-diabetic and diabetic rats by 35 and approximately 10%, respectively, and triglyceride fell by 69 and 20%, respectively, compared with control rats. 3.,Fish oil feeding decreased non-esterified fatty acids (NEFA) by 29% in diabetic rats but the NEFA level in non-diabetic rats was unaffected. 4.,In non-diabetic and diabetic rats, platelet aggregation decreased by 49 and 37%, respectively, and total anti-oxidant status increased by 18 and 17%, respectively, after fish oil feeding. 5.,Insulin levels increased by 27% in the fish oil-fed non-diabetic rats, whereas insulin levels were markedly decreased in diabetic rats. Glucose levels were not altered at all and fructosamine levels decreased by 29% only in fish oil-fed diabetic rats. 6.,The results of the present study suggest that Hilsa ilisa fish oil may ameliorate the atherogenic lipid profile, platelet hyperaggregation and the anti-oxidative defence of STZ-diabetic rats and the amelioration is thought to be independent of the effects of Hilsa on glycaemic control. [source]