Streptozocin-induced Diabetic Rats Research Articles

Endoplasmic reticulum stress is involved in apoptosis of detrusor muscle in streptozocin-induced diabetic rats.

Endoplasmic reticulum stress (ERS) has been proven to be associated with apoptosis and plays a critical role in the development of many diabetic complications. In the pathogenesis of diabetic cystopathy (DCP), the role of ERS is still unclear. Our study is aimed at the investigation of the involvement of ERS-associated detrusor muscle apoptosis in streptozocin (STZ)-induced diabetic rats. At different timepoints (4, 8, 12, and 16 weeks after induction of type 1 diabetic rat models), hematoxylin & eosin (H&E) staining was performed to assess the histological changes of the diabetic detrusor; the sub-cellular ultrastructure, especially the zone of endoplasmic reticulum (ER), was observed by transmission electron microscopy (TEM), and the terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling (TUNEL) staining was used to identify the enhanced apoptosis. Moreover, the expression of three hallmarks of ERS-associated apoptosis, including glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and caspase12, was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Light microscopic impairments of histology, including progressive loosely packed muscle bundles and increased fibrous tissue, can be seen; the ultrastructural changes featuring the swollen and fused cisternaes in ER zone and deformed nucleus were also observed in the detrusor smooth muscle (DSM). Increased apoptosis and elevated expression of GRP78, CHOP, and caspase12 at both protein and mRNA levels in a time-dependent fashion were detected. The occurrence of ERS-associated apoptosis may be involved in the development of DCP and may contribute to the diabetic detrusor impairment. Neurourol. Urodynam. 36:65-72, 2017. © 2015 Wiley Periodicals, Inc.

Promoted Interaction of Nuclear Factor-κB With Demethylated Purinergic P2X3 Receptor Gene Contributes to Neuropathic Pain in Rats With Diabetes.

Painful diabetic neuropathy is a common complication of diabetes produced by mechanisms that as yet are incompletely defined. The aim of this study was to investigate the roles of nuclear factor-κB (NF-κB) in the regulation of purinergic receptor P2X ligand-gated ion channel 3 (P2X3R) plasticity in dorsal root ganglion (DRG) neurons of rats with painful diabetes. Here, we showed that hindpaw pain hypersensitivity in streptozocin-induced diabetic rats was attenuated by treatment with purinergic receptor antagonist suramin or A-317491. The expression and function of P2X3Rs was markedly enhanced in hindpaw-innervated DRG neurons in diabetic rats. The CpG (cytosine guanine dinucleotide) island in the p2x3r gene promoter region was significantly demethylated, and the expression of DNA methyltransferase 3b was remarkably downregulated in DRGs in diabetic rats. The binding ability of p65 (an active form of NF-κB) with the p2x3r gene promoter region and p65 expression were enhanced significantly in diabetes. The inhibition of p65 signaling using the NF-κB inhibitor pyrrolidine dithiocarbamate or recombinant lentiviral vectors designated as lentiviral vector-p65 small interfering RNA remarkably suppressed P2X3R activities and attenuated diabetic pain hypersensitivity. Insulin treatment significantly attenuated pain hypersensitivity and suppressed the expression of p65 and P2X3Rs. Our findings suggest that the p2x3r gene promoter DNA demethylation and enhanced interaction with p65 contributes to P2X3R sensitization and diabetic pain hypersensitivity.

Serum chemerin and insulin sensitivity alterations due to exercise training below and above lactate thresholds in streptozocin-induced diabetic rats

The aim of this study was to investigate serum chemerin and insulin sensitivity alterations due to exercise training below and above lactate thresholds in streptozocin-induced diabetic rats. Twenty-four rats (190 ± 14 g) were randomly assigned to three groups of control (CON), above lactate thresholds (ALT) and below lactate thresholds (BLT) (n = 8). Then after induction of diabetes, BLT and ALT performed an 8-week exercise program on treadmill running (15 and 27 m/min, respectively) at 0° slope, 1 h/day, and 5 days/week. SPSS version 16 was used for data analysis. The findings showed that, BLT serum chemerin decreased −27 % compared to CON that was statistically significant (p = 0.042), fasting Glucose level of ALT was significantly decreased 19 % compared to CON after 8-week training protocol (p = 0.02). Also 24 % significant reduction was observed in BLT in comparison to CON (p = 0.005). Insulin sensitivity of BLT and ALT improved 7 and 5 %, respectively, compared to CON and both were not significant. Also, positive correlationship was observed between fasting plasma glucose and serum chemerin but it was not significant statistically. Negative correlationship was seen between plasma insulin level and chemerin concentrations and it was not significant too. Compared with CON, BLT weight was significantly reduced 12 % (p = 0.012). Also 9 % weight loss was observed in ALT due to 8-week exercise training which was not statistically significant (p = 0.058). In summary, 8-week exercise training below lactate thresholds may reduce serum chemerin and improve fasting glucose levels.

Xuezhikang () reduced renal cell apoptosis in streptozocin-induced diabetic rats through regulation of Bcl-2 family.

To investigate the effect of Xuezhikang (, XZK) on renal cell apoptosis in diabetic rats and the possible mechanism. Sixty-six rats were randomly divided into 3 groups: the normal, model and XZK groups. In each group, the rats were further randomly divided into 3-month and 6-month subgroups, respectively. Diabetes of rats was induced by a single intraperitoneal injection of 1% streptozocin at 60 mg/kg body weight. Rats in the XZK group received gastric perfusion of XZK (1200 mg/kg body weight) everyday for 3 or 6 months, while rats in the normal and model groups received equal volume of saline. Twenty-four hours' urine was collected for urinary albumin excretion (UAE) measurement. Periodic acid-Schiff (PAS) and Masson's trichrome staining were used for saccharides and collagen detection. Cell apoptosis of renal cortex was investigated by TdT-mediated dUTP nick end labeling (TUNEL) staining. Bax and Bcl-2 expressions were detected by immunohistochemistry and Western blot, respectively. Cytochrome C (Cyt C) and caspase-9 concentration were detected by Western blot. Compared with the model group, XZK treatment could significantly decrease the kidney hypertrophy index, 24 h UAE, renal cell apoptosis, cytoplasmic Cyt C level and active caspase-9 level, as well as suppress the increment of Bax and up-regulate the expression of Bcl-2, leading to the suppression of Bax/Bcl-2 ratio at 3 and 6 months (P<0.05 or P<0.01). Moreover, XZK treatment could alleviate the deposition of PAS-stained saccharides and Masson's trichromestained collagen to different extent. Renal cell apoptosis was observed in diabetic kidney, in which mitochondrial apoptotic pathway might be involved. XZK treatment could attenuate pathological changes in diabetic kidney and reduce renal cell apoptosis, probably via the suppression of Bax/Bcl-2 ratio, which lead to inhibition of Cyt C release and following caspase-9 activation.

Effects of Yam Polysaccharides on P-selectin expression and macrophage infiltration in diabetic nephropathy model rats

Objective: Observe effects of Yam polysaccharides on P-selectin (Ps) expression and macrophage infiltration in diabetic nephropathy model rats. Method: Establish a Streptozocin-induced diabetic nephropathy rat model. After successful modeling, the rats are assigned into one of the following groups (10 rats/group): Model Group, Yam Polysaccharides Groups (50, 100, 200 mg·kg -1 ), and Metformin Hydrochloride Tablets (800 mg·kg -1 ) Group. The rats in the Yam Polysaccharides Dose Groups are administered intragastrically, and the rats in the Normal Control Group and the Model Group are administered intragastrically with an equal volume of distilled water, qd, for 8 consecutive weeks. Kidney weights, kidney indexes, 24-h urine protein excretion, blood glucose (Glu), creatinine (Crea), urea nitrogen (BUN), and albumin (ALB) in rats, as well as nitric oxide (NO), malonaldehyde (MDA), and superoxide dismutase (SOD) in kidney homogenate are measured. Changes in the expressions of glomerular Ps, CD68, transforming growth factor β1 (TGF-β1) in rats are observed by immunohistochemistry. Results: Blood glucose and 24-h urine protein excretion

Antihyperglycemic Properties of Foeniculum vulgare Extract in Streptozocin-Induced Diabetes in Rats

Antihyperglycemic Properties of Foeniculum vulgare Extract in Streptozocin-Induced Diabetes in Rats

Caloric restriction and exercise training, combined, not solely improve total plasma adiponectin and glucose homeostasis in streptozocin-induced diabetic rats

The aim of this study was to investigate the effect of exercise training, caloric restriction and combination of caloric restriction with exercise training on plasma concentrations of adiponectin, insulin, and blood glucose in diabetic female rats. Forty, 8-week-old female Wistar rats (189 ± 10 g) were randomly assigned to two group of healthy (n = 8) as control and diabetic candidates (n = 32). Then after induction of diabetes, diabetic group were split up into four groups of Ex, CR and Ex+CR as experimental groups and DC as diabetic control group (n = 8). Then 20 % negative energy balance were administered through caloric restriction, exercise training and in combination for 8 weeks. The intensity was constant (28 m/min) but its time was flexible to adjust negative energy balance (equal to 20 % of their energy intake). Two bout of 35 min was for Ex and two of 40 min for Ex+CR. The finding showed that glucose level of CR and Ex+CR was significantly lower than DC. Also Ex+CR showed a significant increase in plasma total adiponectin comparing to DC. It is concluded that exercise training via caloric restriction has more beneficial effects on fasting glucose and plasma total adiponectin in streptozocin-induced diabetic rats.

Effect of biochanin a on serum visfatin level of streptozocin-induced diabetic rats.

Background:Bioflavonoids are well known for their multi directional biologic activity including antidiabetic effect. It has been demonstrated that flavonoids can act as insulin secretagogue or insulin mimetic agents.Objectives:This experimental study was designed in Arak University of Medical Sciences, Arak, Iran, to investigate the effects of biochanin A (a bioflavonoid) on fasting blood glucose (FBG), body weight, glycosylated hemoglobin (HbA1c), lipid profile, serum enzymes, and visfatin of streptozocin-induced diabetic rats.Patients and Methods:We used 24 male Wistar rats and randomly allocated them to four groups of six rats. One group was randomly assigned as control and diabetes was induced in three other groups by administration of streptozocin (35 mg/kg of body weight) intraperitoneally. The groups received the following treatments: group 1 (control), 5% DMSO; group 2 (diabetic control), 0.5% DMSO; and group 3 and 4, respectively 10 and 15 mg/kg biochanin A for 30 days. Body weight and biochemical parameters including FBG, HbA1c, lipid profile, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and visfatin were measured in all rats.Results:FBG level was significantly reduced in treated diabetic rats (139.8 ± 9.3 and 206 ± 11 mg/dL in groups 3 and 4, respectively) in comparison to the diabetic control (295.1 ± 14 mg/dL) (P < 0.05). Administration of biochanin A significantly decreased HbA1c in group 3 (6.66 ± 0.33) and group 4 (7.11 ± 0.31) in comparison to the diabetic control group (8.26 ± 0.44) (P < 0.05). Levels of serum visfatin were improved to near normal levels in the treated rats (249 ± 35.5 and 161.33 ± 13.07 in groups 3 and 4, respectively) in comparison to the diabetic control (302.17 ± 19.4) (P < 0.05). Furthermore, biochanin A showed a protective effect against weight loss in diabetic rats (P < 0.05). In treated rats, serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol (LDL-c) were significantly decreased and high-density lipoprotein (HDL-c) was increased in comparison with the diabetic control group. In addition, biochanin A restored the altered plasma enzymes (AST, ALT, and ALP) activities to near normal. Histopathologic examination of the pancreas also indicated that biochanin A had protective effects on β-cells in streptozocin-induced diabetic rats.Conclusions:This study demonstrated that biochanin A possessed hypoglycemic and antilipemic activities and could increase visfatin expression, which suggests its beneficial effect in the treatment of diabetes.

Cationic star-shaped polymer as an siRNA carrier for reducing MMP-9 expression in skin fibroblast cells and promoting wound healing in diabetic rats.

BackgroundExcessive expression of matrix metalloproteinase-9 (MMP-9) is deleterious to the cutaneous wound-healing process in the context of diabetes. The aim of the present study was to explore whether a cationic star-shaped polymer consisting of β-cyclodextrin (β-CD) core and poly(amidoamine) dendron arms (β-CD-[D3]7) could be used as the gene carrier of small interfering RNA (siRNA) to reduce MMP-9 expression for enhanced diabetic wound healing.MethodsThe cytotoxicity of β-CD-(D3)7 was investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MMT) method in the rat CRL1213 skin fibroblast cell line. The transfection efficiency of β-CD-(D3)7/MMP-9-small interfering RNA (siRNA) complexes was determined by confocal microscopy and flow cytometry. Quantitative real time (RT) polymerase chain reaction was performed to measure the gene expression of MMP-9 after the transfection by β-CD-(D3)7/MMP-9-siRNA complexes. The β-CD-(D3)7/MMP-9-siRNA complexes were injected on the wounds of streptozocin-induced diabetic rats. Wound closure was measured on days 4 and 7 post-wounding.Resultsβ-CD-(D3)7 exhibited low cytotoxicity in fibroblast cells, and easily formed the complexes with MMP-9-siRNA. The β-CD-(D3)7/MMP-9-siRNA complexes were readily taken up by fibroblast cells, resulting in the downregulation of MMP-9 gene expression (P<0.01). Animal experiments revealed that the treatment by β-CD-(D3)7/MMP-9-siRNA complexes enhanced wound closure in diabetic rats on day 7 post-wounding (P<0.05).Conclusionβ-CD-(D3)7 may be used as an efficient carrier for the delivery of MMP-9-siRNA to reduce MMP-9 expression in skin fibroblast cells and promote wound healing in diabetic rats.

Grape seed extract and Zinc containing nutritional food supplement delays onset and progression of Streptozocin-induced diabetic cataract in Wistar rats.

Prevention of hyperglycemia and enhancement of antioxidant defense mechanisms remain major goals in the treatment of diabetic cataract. Earlier, we reported strong anti-hyperglycemic and in vitro antioxidant potential of the combined formulation of grape seed extract and Zincovit tablets. Therefore, the current study was designed to investigate effects of combined formulation of grape seed extract and Zincovit tablets against streptozocin-induced diabetic cataract in Wistar rats. Adult Wistar rats were selected and diabetes was induced by streptozocin (35mg/kg, i.p) and divided into four groups (group II-V). The normal control (group I) and streptozocin-induced diabetic cataract control rats received only vehicle. Groups III, IV and V animals received orally 40, 80 and 160mg/kg of combined formulation of Zincovit tablets with grape seed extract respectively for a period of 150days. The biochemical pathways involved in the pathogenesis of cataract such as oxidative stress, polyol pathway and alterations in adenosine triphosphate, glucose-6-phosphate dehydrogenase and blood glucose were investigated, to understand the possible mechanism of action of combined formulation of grape seed extract and Zincovit tablets. Rats treated with combined formulation of grape seed extract and Zincovit tablets delayed the progression of diabetic cataract as well as it showed significant alterations in oxidative stress markers along with blood glucose, aldose reductase, glucose-6-phosphate dehydrogenase and adenosine triphosphate level in lens. Over all, the results suggest that single combined formulation of grape seed extract and Zincovit tablets may be of great value in delaying diabetic cataract of human subjects as nutritional food supplement.

Intravitreal Injection of Ranibizumab and CTGF shRNA Improves Retinal Gene Expression and Microvessel Ultrastructure in a Rodent Model of Diabetes

Therapeutic modalities targeting vascular endothelial growth factor (VEGF) have been used to treat neovascularization and macular edema. However, anti-VEGF treatment alone may cause up-regulation of connective tissue growth factor (CTGF) in the retina, increasing the risk of fibrosis and tractional retinal detachment. Therefore, in this study, we employ a novel dual-target intervention that involves intravitreal injection of the VEGF inhibitor ranibizumab and a transfection reagent-treated non-viral vector carrying anti-CTGF short hairpin RNA (shRNA) driven by human RNA polymerase III promoter U6. The effects of the dual-target intervention on the expression of VEGF and CTGF and on microvessel ultrastructure were examined in retina of streptozocin-induced diabetic rats. CTGF was significantly up-regulated at week 8 after diabetic induction, whereas VEGF was not up-regulated until week 10. The high expression of both genes was maintained at week 12. Transmission electron microscopy also revealed progressive exacerbation of microvessel ultrastructure during the same period. In addition, ranibizumab significantly lowered VEGF but elevated CTGF mRNA, whereas CTGF shRNA significantly reduced the mRNA levels of both CTGF and VEGF in diabetic retinas. Importantly, dual-target intervention normalized the transcript levels of both target genes and ameliorated retinal microvessel ultrastructural damage better than either single-target intervention. These results suggest the advantages of dual-target over single-target interventions in diabetic retina and reveal a novel therapeutic modality for diabetic retinopathy.

The Effect of Water Extract of Zataria multiflora on Microvascular Permeability in Streptozocin Induced Diabetic Rats

The Effect of Water Extract of Zataria multiflora on Microvascular Permeability in Streptozocin Induced Diabetic Rats

Iridoid glucoside attenuates hyperglycemia-mediated oxidative stress and thyroid hormone function in streptozotocin–induced diabetic rats

The present study was to evaluate the effect of iridoid glucoside on the levels of blood glucose, plasma insulin, serum total protein, albumin, thyroid hormone (T3, T4), TSH, LPO and activities of both enzymic and non-enzymic antioxidants in streptozocin-induced diabetic rats. The levels of blood glucose, TBARS and hydroperoxide were significantly increased whereas the levels of plasma insulin and activities of enzymic antioxidants (SOD, CAT, GPx and GST) and the levels of non-enzymic antioxidants (vitamin C, vitamin E) and reduced glutathione were decreased in the liver and kidney tissues of diabetic rats. In addition, serum levels of total protein, albumin, T3, T4 and TSH were also decreased in diabetic rats when compared to control rats. Oral administration of iridoid glucoside to diabetic rats showed significant ameliorative effects on all the biochemical parameters studied. Moreover, the iridoid glucoside showed free radical scavenging activity assessed by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) in vitro which may have responsible for these hypoglycemic and improved antioxidant statuses in vivo. The effect produced by iridoid glucoside on various parameters was comparable to that of glibenclamide. These results indicated that iridoid glucoside possesses antidiabetic and antioxidant potential in addition to synthesis and/or secretion of circulating thyroid hormone.

Febuxostat contributes to improvement of endothelial dysfunction in an experimental model of streptozocin-induced diabetic rats

Febuxostat contributes to improvement of endothelial dysfunction in an experimental model of streptozocin-induced diabetic rats

Effect of Oral Administration of Magnesium on Cisplatin-Induced Nephrotoxicity in Normal and Streptozocin-Induced Diabetic Rats

BackgroundCisplatin (CP) therapy as the most common potent chemotherapeutic process is accompanied by nephrotoxicity. The diabetic state may protect rat kidney against this toxicity, and magnesium (Mg) on the other hand may reduce the glucose level in diabetic animals.ObjectivesCurrent study was planned to investigate the effect of oral administration of magnesium supplementation on CP-induced nephrotoxicity in normal and Streptozocin (STZ)-induced diabetic rats.Materials and MethodsMale Wistar rats were divided into seven groups and underwent two experiment protocols. As protocol 1, group 1 was considered as the sham group. Group 2 (CP group) received CP (2 mg/kg/d) for five consecutive days. Group 3 (CP + Mg group) received magnesium sulphate (MgSO4, 10 g/L added to the drinking water) for 10 days and then treated with CP from sixth day. As protocol 2, animals received a single dose of STZ (65 mg/kg i.p.). Three days after diabetes induction, animals were divided into four groups; Groups 4 (D group), 5 (D + CP group), and 7 (D + Mg + CP group) followed the same manner as groups 1 to 3, respectively; and group 6 (D + Mg group) was treated with MgSO4 alone for 10 days. Finally, blood samples were obtained, and all animals were killed for kidney tissue investigation.ResultsCP administration in normoglycemic rats significantly elevated the serum levels of blood urea nitrogen (BUN) and creatinine (Cr) (P < 0.05). However, coadministration of CP and Mg statistically increased the serum levels of BUN and Cr in both normoglycemic and diabetic animals when compared to the rats treated with CP alone (P < 0.05), while the serum level of Mg was significantly increased in nondiabetic groups (P < 0.05). No significant changes were observed in serum and kidney levels of nitrite; as well as the testis weight between all normoglycemic groups, whereas Mg decreased kidney levels of nitrite in diabetic groups when accompanied by CP (P < 0.05). The kidney and serum levels of malondialdehyde (MDA) enhanced significantly in nondiabetic rats treated with Mg and CP (P < 0.05). Kidney tissue damage score (KTDS), kidney weight, and body weight loss were significantly different among normoglycemic groups (P < 0.05), and Mg promoted the KTDS in diabetic animals treated with CP.ConclusionsOral Mg supplementation did not protect the CP induced nephrotoxicity in diabetic rats.

Comment on: Preventive effect of Teucrium polium on learning and memory deficits in diabetic rats

We read with great interest the article by Hasanein and colleagues in the Medical Science Monitor Journal, entitled “Preventive effect of Teucrium polium on learning and memory deficits in diabetic rats” [1]. They aimed to investigate passive avoidance learning and memory in control and streptozocin-induced diabetic rats treated with an aqueous extract of Teucrium polium. Impairment in acquisition of passive avoidance learning and retrieval of memory was seen by inducing diabetes. Teucrium polium treatment (200 and 400 mg/kg) improved learning and memory in control rats and reversed learning and memory deficits in diabetic rats. They concluded that Teucrium polium prevented the deleterious effects of diabetes on passive avoidance learning and memory. The authors suggested that antioxidant, anticholinesterase, and hypoglycemic effects of Teucrium polium may be involved in the obtained effects. They also concluded that Teucrium polium appears to be a promising candidate for memory improvement in diabetes [1]. We would like to point out a few comments about this paper. To test the possible renal toxicity of hydroalcoholic extract of Teucrium polium, we recently studied 100 male Wistar rats [2] divided into 10 groups of 10 each. Five groups were injected intraperitoneally (IP) with 50, 100, 150, and 200 mg/kg extracts and normal saline for 28 days and killed to examine the probable kidney damage. Five other groups were injected according to the same drug regimen, but they were killed 28 days after discontinuation of Teucrium polium injections to investigate possible renal complications or regeneration during recovery. After 28 days of receiving Teucrium polium (Phase I), renal injury were not increased in comparison with the control group. However, kidney injury, including degeneration, destruction, and vacuolization [3–5] appeared 28 days after drug cessation. We concluded that Teucrium polium may be associated with kidney tubular injury and that this herbal medicine should be used with caution [2]. It is well known that herbal remedies have an important role in the recovery of some disease [6–9]; however, some medicinal plants can cause renal injury. Teucrium polium has been widely used to control blood sugar in diabetes [7]. Hence, according to our results concerning its renal tubular cell toxicity, it needs much attention to re-evaluate its use. Indeed, information about successful effect on prevention or amelioration of a medicinal drug requires knowledge the adverse effects, mainly on kidney or liver [10–17]. In this regard, to better understand the hepatic and renal effects of T. polium, more experimental or clinical studies are suggested.

Alpha-Linolenic Acid Exerts an Endothelial Protective Effect against High Glucose Injury via PI3K/Akt Pathway

Mounting evidence has indicated that the cardiovascular protective effects of dietary alpha-linolenic acid (ALA), but whether ALA exerts an endothelial protective effect against high glucose injury and the underlying mechanisms remain largely unknown. Streptozocin-induced diabetic rats were randomized treated orally for 4 weeks with vehicle (0.01% alcohol) or ALA (500 µg/kg per day by gavage). Human umbilical vein endothelial cells (HUVECs) were exposed to high glucose (28 mmol/L) stimulation for 48 hours. ALA significantly improved concentration-dependent vasorelaxation to ACh in diabetic aortic segments and inhibited endothelial inflammation as evidenced by decreased soluble P-selectin and intercellular adhesion molecule-1 (ICAM-1) in diabetic rats. Furthermore, both P-selectin and ICAM-1 expression were increased significantly in high glucose-induced HUVECs, resulting in enhanced neutrophils adhesion to HUVECs compared with normal glucose group. Treatment with ALA (50 µmol/L) increased Akt phosphorylation, attenuated P-selectin and ICAM-1 expressions and thus inhibited neutrophils adhesion in HUVECs exposed to high glucose, all of which was blocked by the PI3K inhibitors LY294002 and wortmannin. These data indicates that ALA inhibits endothelial inflammation and improved endothelial function in STZ-induced diabetic rats. The anti-adhesive effect of ALA against high glucose injury may partially be mediated by the PI3K/Akt pathway.

Smooth muscle cell transplantation improves bladder contractile function in streptozocin-induced diabetic rats

Background aimsDamage to smooth muscle has been the primary cause of dysfunction in diabetic bladders. Major changes in the filling phase of the bladder result in the loss of compliance and incomplete emptying in patients. MethodsCell-based therapies in the lower urinary tract have shown promising results. We argue that because diabetic bladder dysfunction is primarily a problem arising out of altered smooth muscle cells (SMCs), it would be an interesting approach to introduce healthy SMCs into the bladder wall. ResultsFurthering this hypothesis, in this experiment, we were successful in introducing syngeneic, healthy SMCs into diabetic bladders. We attempted a method wherein bladder function can be improved in streptozocin-induced diabetes mellitus. Ex vivo–cultured healthy SMCs were introduced into the diabetic bladders of syngeneic Sprague-Dawley rats during the hypercontractile phase after induction of diabetes. Cystometry, metabolic cage evaluation, organ bath studies and histological analyses were performed on the healthy control, the diabetic and the diabetic group transplanted with SMCs. ConclusionsDuring the 2-week follow-up period after transplantation, we noticed an increase in contractile response of the bladder correlating to a decrease in residual urine. Cell survival studies revealed a cell survival rate close to 1.5%.

Verapamil reverses cardiac iron overload in streptozocin-induced diabetic rats

Accumulating evidence shows that iron overload is a new risk factor for diabetes mellitus. L-type Ca(2+) channel (LTCC) has been identified as an important mediator for ferrous iron uptake into cardiomyocytes. In this study, we aimed to examine the effects of verapamil, the LTCC blocker, on myocardial iron metabolism in diabetic rats. Diabetes was induced by intraperitoneal injection of streptozocin after intragastric administration of fat emulsion, and then treated by verapamil (5 mg · kg(-1) · day(-1)) for 1 week. The results showed that verapamil did not alter the blood glucose level of diabetic rats. However, elevated levels of superoxide dismutase, malonaldehyde, and serum ferritin in diabetic rats were decreased significantly by verapamil treatment. Moreover, serum, myocardial, and urine iron were elevated remarkably along with a decrease of hepatic iron in diabetic rats. After verapamil administration, serum and myocardial iron in diabetic rats were reduced significantly but urine and hepatic iron were increased. Furthermore, confocal microscopy demonstrated that intracellular-free iron concentration was elevated dramatically in cardiomyocytes of diabetic rats, which was markedly attenuated after verapamil treatment. In summary, our data demonstrated that verapamil prevented myocardial iron overload by inhibiting intracellular iron accumulation in diabetic cardiomyocytes.

Antioxidant and Antihyperlipidemic Effects of the Aqueous Extract from Ficus Deltoidea var. Kunstleri Fruit and its Water Fraction IN Streptozocin-Induced Diabetic Rats

Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia; Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia; University Malaya Centre for Proteomics Research (UMCPR), Medical Biotechnology Laboratory, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia; E-mail: hasni@um.edu.my