Weeks Of Streptozotocin Injection Research Articles

Effect of Lycopene alone and along with Coenzyme-Q10 in Streptozotocin Induced Peripheral Neuropathy: Biochemical & Behavioural Study

Diabetic Neuropathy (DN) is major chronic consequences of the diabetes. DN is developed due to chronic hyperglycemia which is related with generation of oxidative stress (OS) and alteration in the neuronal function. This study was envisaged to find the desirable neuroprotective outcomes of natural antioxidants i.e., lycopene and coenzyme Q10 (CoQ10) as monotherapy or concomitant administration in rats subjected to DN induced by streptozotocin (STZ). Single subcutaneous dose of STZ (55 mg/kg) was used to induce DN in male wistar rats (200–250 g). Significant neuropathy was observed after four weeks of streptozotocin injection. Neuropathy was evaluated by behavioral parameters using mechanical allodynia, mechanical hyperalgesia, heat/thermal hyperalgesia and walking track analysis. Oxidative stress was determined by assessment of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and nitric oxide (NO) in homogenate of sciatic nerve. STZ significantly alters all the behavioral as well as biochemical parameters. Treatment with lycopene (5mg/kg/p.o.), CoQ10 (10mg/kg, p.o.) and their combination for four weeks significantly reduced blood glucose level. The behavioural and biochemical alteration was significantly improved with the combination of lycopene and CoQ10. The combination of both the antioxidants significantly reversed the streptozotocin induced neuropathy in rats compared to alone antioxidants as well as diabetic neuropathy group. It is concluded that neuroprotective effect of lycopene, CoQ10 alone and in combination might be due to their strong antioxidant property.

Inhibition of NF-κB ameliorates aberrant retinal glia activation and inflammatory responses in streptozotocin-induced diabetic rats.

To determine the anti-inflammatory effects of IMD-0354, a specific NF-κB blocker, on glial cells in rats with streptozotocin (STZ)-induced diabetic retinopathy (DR). The following four groups of rats were used: control, control + IMD-0354, STZ, and STZ + IMD-0354. After six weeks of STZ injection, diabetic rats and nondiabetic control rats received IMD-0354 (30 mg/kg) or an equal volume of 4% dimethyl sulfoxide (DMSO) in phosphate-buffered saline intraperitoneally for six consecutive weeks. The following four groups of primary rat retinal microglia and Müller cells were used: control (5 mM), control + IMD-0354, high glucose (20 mM), and high glucose + IMD-0354. The effects of IMD-0354 on nuclear factor-κB (NF-κB) activation, oxidative stress strength, expression of inflammatory cytokines and VEGF (vascular endothelial growth factor), activation of glial cells, and apoptosis of neuron cells were evaluated by immunohistochemistry, oxidative stress assays, western blot, enzyme linked immunosorbent assay (ELISA) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining respectively. Nuclear translocation of NF-κB was markedly increased in diabetic rat retina and high glucose treated glial cells. Systemic administration of IMD-0354 significantly inhibited NF-κB activation in both diabetic rat retina and high glucose treated glial cells, ameliorated oxidative injury, inflammatory responses, VEGF production and glial cell activation, and protected neurons from apoptosis. Our findings indicated that NF-κB activation is acritical step in the abnormal reactivity of glial cells in STZ-induced diabetic rats. Inhibition effect of IMD-0354 on NF-κB activation may represent a promising therapeutic strategy for DR via a variety of mechanisms, including inflammation reduction and glial cells regulation.

MitoTEMPOL modulates mitophagy and histopathology of Wistar rat liver after streptozotocin injection.

This study aims to explore the effect of mitoTEMPOL on histopathology, lipid droplet, and mitophagy gene expression of Wistar rat's liver after injection of streptozotocin (STZ). Twenty male Wistar rats were divided into 4 groups: Control (n=5); 100 mg/kg BW/day mitoTEMPOL orally (n=5); 50 mg/kg BW STZ intraperitoneal injection (n=5); and mitoTEMPOL+STZ (n=5). STZ was given a single dose, while mitoTEMPOL was given for 5 weeks after 1 week of STZ injection. Histopathological appearance, lipid droplets, mitophagy, and autophagy gene expression were examined after the mitoTEMPOL treatment. We found metabolic zone shifting that might be correlated with the liver activity of fatty acid oxidation in the STZ group, a decrease of lipid droplets in mitoTEMPOL and mitoTEMPOL + STZ compared with Control and STZ groups were found in this study. We also found significant changes in PINK1, Parkin, BNIP3, Mfn1, and LC3 gene expression, but no difference in Opa1, Fis1, Drp1, and p62 gene expression, suggesting a change of mitochondrial fusion rather than mitochondrial fission correlated with mitophagy. All this concluded that mitoTEMPOL could act as a modulator of mitophagy and metabolic function of the liver, thus amplifying its crucial role in preventing mitochondrial damage in the liver in the early onset of diabetes mellitus.

Inhibitory Effect of Insulin Treatment on Apoptosis of Intervertebral Disc Cells in a Streptozotocin-Induced Diabetic Rat Model.

Experimental study using a streptozotocin (STZ)-induced diabetic rat model. This study aims to investigate whether insulin treatment could attenuate disc cell apoptosis and matrix degradation in a STZ-induced diabetic rat model. Diabetes is a significant risk factor for disc degeneration due to excessive apoptosis of disc cells and matrix degradation. However, no studies were noted to demonstrate the inhibitory effect of insulin treatment on the apoptosis of disc cells and matrix degradation in diabetic patients. Rats were allocated randomly into one of three groups: control, STZ, and STZ-insulin. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in the STZ and STZ-insulin groups. The blood glucose level was consistently above 400 mg/ dL in the STZ and STZ-insulin groups 2 weeks after STZ injection. After 2 weeks of STZ injection, the STZ-insulin group was administered insulin treatment (1.5 unit/100 g) daily for up to 4 weeks. Blood glucose of the STZ-insulin rats significantly decreased to normal levels 4 weeks after insulin treatment. The rats were sacrificed 6 weeks after STZ injection, and disc cells and tissues were harvested to investigate the expression of apoptosis markers and matrix metalloproteinases (MMPs). Fas and caspase-8, -9, and -3 expressions were significantly increased in the STZ group, along with increased expressions of MMP-2 and -3. On the contrary, insulin treatment significantly decreased the expressions of Fas, caspase-8, -9, and -3 as well as MMP-2 and -3 in the STZ-insulin group. The results of the current study demonstrated that insulin treatment attenuates excessive apoptosis of disc cells and matrix degradation in the diabetic rat model. Accordingly, strict blood glucose control should be recommended to prevent disc degeneration in diabetic patients.

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In diabetes, one of the most important causes of morbidity and mortality is vasculopathy. Though flaxseed (FXS) is known for improving cardiovascular health, only limited studies are available on FXS concerning diabetic vascular reactivity. Hence, in this study, we studied vascular reactivity changes after FXS treatment on streptozotocin (STZ)-induced diabetic rat aortae. Female Wistar rats were divided into following four groups: control (C), FXS treated (CT), diabetic (D), and FXS treated diabetic (DT) groups. FXS (0,714 g/kg/day; orally) was started after one week of STZ injection and was given for 12 weeks, phenylephrine (Phe)-induced contractions were obtained on isolated aortic rings in the presence of indomethacin, L-NAME and superoxide dismutase (SOD), individually. Phe-responses were increased significantly in D group and completely improved after FXS intake, whereas FXS increased vascular reactivity to Phe in C group. Indomethacin incubation significantly attenuated Phe-induced contractions in all groups of aorta, particularly in D group. L-NAME incubation significantly increased Phe responses in all groups except D group. SOD incubation decreased the contractions efficiently in D group. The decreament was much lower in DT compared to D group, but reverse effects were observed in CT group. Our findings suggest FXS may provide beneficial effects on diabetes-induced vascular reactivity changes through NO and prostaglandin dependent pathways, but in healty condition FXS may have adverse effect probably via pro-oxidant activity.

Altered Renal Pathology in an Autoimmune Disease Mouse Model After Induction of Diabetes Mellitus.

Diabetes mellitus (DM) is a predisposing factor for renal disorder progression and is referred to as diabetic kidney disease (DKD). However, there are no reports of DKD with an underlying autoimmune disorder. In this study, we compared the pathophysiological changes caused by DM induction after streptozotocin (STZ) injection in comparison with that in a control group receiving citrate buffer (CB) in the autoimmune disease model mice “BXSB/MpJ-Yaa” (Yaa) and the wild-type strain BXSB/MpJ. Both strains showed hyperglycemia after 12 weeks of STZ injection. Interestingly, the Yaa group developed membranous and proliferative glomerulonephritis, which tended to be milder glomerular lesions in the STZ group than in the CB group, as indicated by a decreased mesangial area and ameliorated albuminuria. Statistically, the indices for hyperglycemia and autoimmune abnormalities were negatively and positively correlated with the histopathological parameters for mesangial matrix production and glomerular proliferative lesions, respectively. STZ treatment induced renal tubular anisonucleosis and dilations in both strains, and they were more severe in Yaa. Significantly decreased cellular infiltration was observed in the Yaa group compared to the CB group. Thus, in DKD related to autoimmune nephritis, hyperglycemia modifies its pathology by decreasing the mesangial area and interstitial inflammation and aggravating renal tubular injury.

PET Imaging of Vesicular Monoamine Transporter 2 in Early Diabetic Retinopathy Using [18F]FP-(+)-DTBZ.

Diabetic retinopathy (DR) is characterized by dopaminergic neuron loss in the retina of the eyes. [18F]fluoropropyl-(+)-dihydrotetrabenazine ([18F]FP-(+)-DTBZ) positron emission tomography (PET) has been shown to detect dopaminergic neuron loss. The study is to investigate the feasibility of PET imaging with [18F]FP-(+)-DTBZ for early diagnosis of diabetic retinopathy (DR) in diabetes mellitus (DM) rat models. The DM rat model was established by a single intraperitoneal injection of streptozotocin (STZ) (65 mg/kg). After 4 weeks, 8 weeks, and 12 weeks of STZ injection, the retinas of the rats were evaluated by electroretinogram (ERG), color fundus photography (CFP), fundus fluorescein angiography (FFA), and small animal PET scan with [18F]FP-(+)-DTBZ by targeting vesicular monoamine transporter 2 (VMAT2). [18F]FP-(+)-DTBZ uptake in retina was quantified as standardized uptake value (SUV). Immunofluorescence staining and Western blot were also performed to confirm the expression level of VMAT2 in retina. ERG dysfunction was observed at 8 weeks in STZ-diabetic rats, evidenced by smaller amplitudes of oscillatory potentials (OPs) when compared with OPs in normal rats. CFP and FFA showed no significant difference in vascular leakage and neovascularization between STZ-diabetic retinas and normal ones until 8 weeks. PET imaging revealed that the SUV of [18F]FP-(+)-DTBZ was significantly lower in the STZ-diabetic retinas compared with the normal ones as early as of week 4. The results from immunofluorescence staining and Western blots confirmed the early findings in PET imaging studies. Early DR can be non-invasively detected with PET imaging using [18F]FP-(+)-DTBZ targeting VMAT2. The expression level of VMAT2 in retina may act as a new biomarker for early DR diagnosis.

MiR-222 inhibits cardiac fibrosis in diabetic mice heart via regulating Wnt/β-catenin-mediated endothelium to mesenchymal transition.

miR-222 participates in many cardiovascular diseases, but its effect on cardiac remodeling induced by diabetes is unclear. This study evaluated the functional role of miR-222 in cardiac fibrosis in diabetic mice. Streptozotocin (STZ) was used to establish a type 1 diabetic mouse model. After 10 weeks of STZ injection, mice were intravenously injected with Ad-miR-222 to induce the overexpression of miR-222. miR-222 overexpression reduced cardiac fibrosis and improved cardiac function in diabetic mice. Mechanistically, miR-222 inhibited the endothelium to mesenchymal transition (EndMT) in diabetic mouse hearts. Mouse heart fibroblasts and endothelial cells were isolated and cultured with high glucose (HG). An miR-222 mimic did not affect HG-induced fibroblast activation and function but did suppress the HG-induced EndMT process. The antagonism of miR-222 by antagomir inhibited HG-induced EndMT. miR-222 regulated the promoter region of β-catenin, thus negatively regulating the Wnt/β-catenin pathway, which was confirmed by β-catenin siRNA. Taken together, our results indicated that miR-222 inhibited cardiac fibrosis in diabetic mice via negatively regulating Wnt/β-catenin-mediated EndMT.

Activation of 20-HETE/PPARs involved in reno-therapeutic effect of naringenin on diabetic nephropathy

Naringenin is a flavanone compound found in citrus fruits. Recent researches showed that naringenin has many potentially pharmacological effects. However, the therapeutic effect and the potential mechanism of naringenin on diabetic nephropathy (DN) remain to be elucidated. DN model was established by a high-fat diet combined with streptozotocin (STZ), which was confirmed by the levels of fasting blood glucose (FBG, more than 11.1 mmol/L) and urinary albumin (10 times higher than the normal mice). After 5 weeks of STZ injection, the DN was developed in model mice. Then naringenin (25 or 75 mg/kg·d) were supplemented for 4 weeks. At the end of the experiment, the injury of the renal function and structure was deteriorated. Concomitantly, peroxisome proliferators-activated receptors (PPARs) protein expression was down-regulated, and CYP4A expression and 20-hydroxyeicosatetraenoic acid (20-HETE) level were reduced in DN mice. Naringenin administration improved the renal damage of DN mice, and up-regulated PPARs expression, increased CYP4A-20-HETE level. Consistent with the results of in vivo, glucose at 30 mmol/L (high glucose, HG) significantly induced cell proliferation and hypertrophy in NRK-52E cells, following the reductive PPARs protein expression and the downward CYP4A-20-HETE level. Naringenin (0.01, 0.1, 1 μmol/L) reversed these changes induced by HG in a dose-dependent manner. HET0016, a selective inhibitor of 20-HETE synthase, partially blocked the effects of naringenin. In conclusion, naringenin has a therapeutic effect on DN, which may be, at least partly, related to the activation of CYP4A-20-HETE and the up-regulation of PPARs.

Ameliorative effects of bee pollen and date palm pollen on the glycemic state and male sexual dysfunctions in streptozotocin-Induced diabetic wistar rats

This study aimed to assess the effects of bee pollen (BP) and/or date palm pollen (DPP) suspensions on the glycemic state, testicular dysfunctions, oxidative stress and antioxidant defense system in streptozotocin (STZ)-induced diabetic male Wistar rats. Diabetes mellitus was induced by single intraperitoneal injection of STZ to overnight-fasted rats at dose of 40mg/kg body weight. After 1 week of STZ injection, diabetic rats were treated with BP and/or DPP suspensions at dose levels of 100mg/kg body weight/day for 4 weeks. The STZ-induced diabetes significantly increased blood glucose levels and testicular nitric oxide (NO) and malondialdehyde (MDA) levels parallel with disrupted testicular and pancreatic histological architecture and integrity. On the other hand, STZ-induced diabetes significantly decreased body weight, testis and pancreas weights, levels of serum insulin, testosterone, luteinizing hormone (LH) & follicle stimulating hormone (FSH) as well as sperm count, motility and viability. The administration of BP and DPP suspensions resulted in a significant recovery of the above mentioned parameters as compared to the diabetic control group. These improvements were associated with enhancement of the testicular antioxidant system manifested by an increase in the lowered glutathione content (GSH) and glutathione-S-transferase (GST), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities in diabetic rats as a result of treatments with BP and DPP suspensions. Thus, it can be concluded that BP and/or DPP suspensions may have potential protective role against diabetes-induced pituitary testicular axis dysfunction and testicular histological deleterious changes in association with antihyperglycemic actions via their antioxidant properties and their efficiency to improve blood insulin level and beta cell function.

Anti-Diabetic Activity of a Polyherbal Formulation in Streptozotocin Induced Type 2 Diabetic Rats

The aim of the present study was to determine the anti-diabetic activity of a polyherbal formulation in streptozotocin induced type 2 diabetic rats. The hydroalcoholic extracts of Eugenia jambolana, Gymnema sylvestre, Momordica charantia and Andrographis paniculata and sodhana processed extract of Myristica fragrans were prepared. The 2 day old neonatal rats were injected with 90 mg/kg of streptozotocin intraperitoneally to induce type 2 diabetes. After six weeks of streptozotocin injection, polyherbal formulation was daily administered at a dose of 400 mg/kg body weight to diabetic rats for a period of 28 days. Blood samples were collected from the retro orbital plexus of the eye and blood glucose level was estimated by glucose oxidase-peroxidase method. The study indicated that polyherbal formulation at a dose of 400 mg/kg body weight showed significant decline (p<0.001) in blood glucose level.

Abstract 410: Novel Sulfonylhydrazone Derivative Prevents Cardiac and Vascular Remodeling in Rats With Streptozotocin-induced Diabetes

Objectives: Investigate the effects of LASSBio-1773, a ligand of PPAR-gamma receptor with hypoglycemic activity, in a model of diabetic cardiomyopathy (DC) induced by streptozotocin (STZ). Methods: Male Wistar rats received a single i.v. injection of STZ (60 mg/kg) for diabetes induction. Experimental groups were: control, STZ + vehicle, and STZ + LASSBio-1773 (50 mg/kg/day i.p.). Animals were treated with vehicle or LASSBio-1773 for 7 days after disease onset. Cardiovascular function and plasma biochemistry evaluations were performed by the end of protocol. Findings: Serum glucose, total cholesterol and triglycerides levels were significantly higher in STZ group, and treatment with LASSBio-1773 normalized both hyperglycemia and hypertriglyceridemia (Table 1). Following 8 weeks of STZ injection, echocardiography showed that left ventricular (LV) filling pressures (E/e′) increased in STZ + vehicle group. Treatment with LASSBio-1773 improved diastolic parameters in STZ-injected rats but no changes were observed on LV ejection fraction (Table 1). STZ + vehicle group have developed hypertension which was reduced after treatment with LASSBio-1773 (Table 1). Vascular dysfunction was found by the reduced acetylcholine maximum relaxation (Ach-MR) in isolated aortic rings from STZ + vehicle group which was improved with LASSBio-1773 administration. Conclusions: LASSBio-1773 improved cardiovascular function and lipid profile of diabetic rats, indicating that this novel PPAR-gamma agonist is a promising candidate for the treatment of diabetes-related cardiac complications.

Activation of angiotensin-converting enzyme 2 improves cardiac electrical changes in ventricular repolarization in streptozotocin-induced hyperglycaemic rats.

Diabetic patients present a high level of cardiac arrhythmias and risk of cardiac sudden death. The renin-angiotensin system (RAS) plays a key role in diabetes and cardiac diseases. The present study aimed to evaluate whether an angiotensin-converting enzyme 2 (ACE2) activator, diminazene aceturate (DIZE), could improve the streptozotocin (STZ)-induced electrical changes in ventricular repolarization in hyperglycaemic rats. Hyperglycaemia was induced in Wistar male rats with STZ (60 mg/kg/iv). After 4 weeks of STZ injection, rats were daily treated with saline (control) or DIZE (1 mg/kg/gavage) for four consecutive weeks. The cardiac electrical function was evaluated in vivo by electrocardiogram and in vitro by cardiac action potential records in different pacing frequencies. Treatment with DIZE was not able to reverse hyperglycaemia nor body weight loss. However, DIZE reversed hyperglycaemia-induced cardiac electrical changes in ventricular repolarization. Specifically, animals treated with DIZE showed shorter QT and QTc intervals. In addition, ACE2 activation was capable to shorten the cardiac action potential and also reverse the arrhythmic markers. Diminazene aceturate treatment did not induce arrhythmic events in normal, as well as in hyperglycaemic animals. Our data indicate that activation of ACE2 has a beneficial effect in hyperglycaemic rats, improving the cardiac electrical function. Thus, DIZE represents a promising new therapeutic agent to treat hyperglycaemia-induced cardiac electrical changes in ventricular repolarization.

Acute administration of diosgenin or dioscorea improves hyperglycemia with increases muscular steroidogenesis in STZ-induced type 1 diabetic rats

Acute dehydroepiandrosterone (DHEA) administration improves hyperglycemia in rats with streptozotocin (STZ)-induced type 1 diabetes mellitus. Diosgenin, a steroid structurally similar to DHEA (dehydroepiandrosterone), is contained highly levels in dioscorea; however, it is still unclear whether this natural product improves hyperglycemia in the type 1 diabetes model rats through an increase muscular GLUT4 signaling. After 1 week of STZ injection, fasting glucose level was measured in blood taken from the tail vein every 30min for 150min after injection of diosgenin or dioscorea (3mg/kg). On another day, muscle was resected 150min after diosgenin or dioscorea injections. Serum DHEA level increased significantly 120min after diosgenin or dioscorea injections; concomitantly, blood glucose level decreased significantly. Moreover, GLUT4 translocation, as well as phosphorylation of Akt and PKC ζ/λ, increased significantly by diosgenin or dioscorea administration. However, these effects of diosgenin and dioscorea were blocked by a 5α-reductase inhibitor that inhibits synthesizing dehydrotestosterone (DHT) from testosterone. Additionally, significant correlations were observed between blood glucose level, GLUT4 translocation level, and muscular sex steroid hormone level 150min after the administrations. These results suggest that the diosgenin-induced increase in the DHEA level may contribute to the improvement of hyperglycemia by activating the muscular GLUT4 signaling pathway in type 1 diabetes model rats.

Protective effect and mechanism of Ginkgo biloba extract-EGb 761 on STZ-induced diabetic cardiomyopathy in rats.

Diabetes mellitus (DM) is a complex metabolic disorder which leads to development of various long-term complications including cardiomyopathy. Oxidative stress due to hyperglycemia plays a key role in the development and progression of diabetic cardiomyopathy (DC). Oxidative stress causes the opening of mitochondrial permeability transition pore (mPTP) eventually leading to myocardium dysfunction. The Ginkgo biloba extract (EGb 761) has antioxidant and mitochondrial membrane potential stabilizing property. Therefore, this study was designed to evaluate the effect of EGb 761 and its possible mechanism of action in DC.Materials and Methods:DM was induced by single injection of Streptozotocin (STZ) (50 mg/kg, i.p.) and cardiac dysfunction was developed on 8th weeks after STZ injection. Cardiac dysfunction was assessed by measuring left ventricle weight/body weight (LVW/BW) ratio, left ventricle (LV) collagen content, LV protein content, serum lactate dehydrogenase (LDH) level.Results:EGb 761 treatment (started after 7th week of STZ injection and continued for 3 weeks) attenuated cardiac dysfunction in diabetic rats as evidenced by a decrease in LV collagen content, protein content, LVW/BW ratio, serum LDH level. Moreover, EGb 761 attenuated the oxido-nitrosative stress (thiobarbituric acid reactive substances, superoxide anion generation, myocardium nitrite) and concomitantly improved the antioxidant enzyme (reduced glutathione) level as compared to untreated diabetic rats. However, protective effect of EGb 761 was inhibited by atractyloside (mPTP opener) that was given for 3 weeks, 30 min before the EGb 761 treatment. These results indicate that EGb 761 corrects diabetic cardiac dysfunction probably by its direct radical scavenging activity and its ability to inhibit the opening of mPTP channel since the cardioprotective effect of EGb 761 was completely abolished by atractyloside.

CHARACTERIZATION OF A RAT MODEL OF INSULIN DEFICIENCY INDUCED VASCULAR COMPLICATION

Vascular dysfunction is one of the important diabetic complications. Here we fully characterized a rat model of streptozotocin (STZ) induced vascular complication. Diabetes was induced by single intraperitoneally injection of STZ (50 mg.kg-1, ip).Blood pressure (BP) and isolated aorta responses phenylephrine (PE), KCl, acetylcholine (ACh), sodium nitroprusside (SNP) were recorded after 6, 8 and 10 weeks of STZ injection.In addition, serum levels of glucose, tumor necrosis factor α (TNFα), lipids, advancedglycation end products (AGEs), and arginase activity were determined. Furthermore, aortic reactive oxygen species(ROS) generation, hemeoxygenase-1 expression and collagen deposition were examined. Streptozotocin injection resulted in a significant hyperglycemia after 3 days of injection which was stable for 10 weeks. Diabetes was associated with a significant increasein BP after 6 weeks which was stable at 8 weeks. Aorta isolated from diabetic animals showed exaggerated contractility to PE and KCland impaired relaxation to ACh compared to control after 6 weeks which were clearer at 8 weeks of STZ injection. In addition, diabetic animals showed significant increases in serum levels of lipids, AGEs, TNFα and arginase enzyme activity after 8 weeks of STZ compared to control. Furthermore, aortae isolated from diabetic animals were characterized by increased ROS generation and collagen deposition. In conclusion, injecting rats with STZ at dose 50 mg.kg-1 produces a model of diabetic vascular complication after 8 weeks that are characterized by hypertension, disturbed vascular reactivity, elevated serum lipids, inflammatory cytokines and enzymes and enhanced aortic ROS generation and collagen deposition. Key words: Diabetes; aorta; hypertension; vascular reactivity, rat Abbreviations: ANOVA, analysis of variance; NO, nitric oxide; PE, phenylephrine; ROS, reactive oxygen species; SNP, sodium nitroprusside;Ach, acetyl choline; BP, blood pressure.

Carvacrol Attenuates Diabetes-Associated Cognitive Deficits in Rats

Carvacrol (CAR), a naturally occurring phenolic monoterpene, has been demonstrated to possess various biological actions. The present study was designed to investigate the neuroprotective effect of CAR on diabetes-associated cognitive deficit (DACD) in a rat model of diabetes and exploring its potential molecular mechanism. Diabetic rats were treated with CAR by the doses of 25, 50, and 100 mg/kg for 7 weeks. Morris water maze was used for behavioral evaluation of memory. Cytoplasmic and nuclear fractions of cerebral cortex and hippocampus were prepared for the quantification of oxidative stress (MDA, SOD, and GSH), NF-κB p65 unit, TNF-α, IL-1β, and caspase-3. After 7 weeks of streptozotocin injection, the rats produced remarkable increase in escape latency, coupled with increased oxidative stress (increased MDA level and decreased SOD as well as reduced GSH), NF-κB p65 unit, TNF-α, IL-1β, and caspase-3 in different regions of diabetic rat brain. Interestingly, coadministration of CAR significantly and dose-dependently prevented behavioral, biochemical, and molecular changes associated with diabetes. In summary, our findings provide the first evidence that CAR can remarkably attenuate DACD and suggest the involvement of oxidative stress, inflammation, and apoptotic cascades in the development of cognitive impairment caused by diabetes. The pharmacological effect of CAR suggests that it may be used as a promising agent for the treatment of conventional antihyperglycemic regiments as well as DACD.

Renoprotective effects of oryzanol in an animal model of experimentally induced diabetic nephropathy

Hyperglycemia-mediated oxidative stress is an important causal factor for the development and progression of diabetic nephropathy. Hence, the present study was hypothesized to explore the renoprotective potential of oryzanol, a commercially-important antioxidant component isolated from crude rice bran oil, in diabetes-induced experimental nephropathy. Wistar rats were administered streptozotocin (45 mg/kg i.v., once) to induce experimental diabetes mellitus. Animals were then divided into the following groups; normal control rats, diabetic rats, diabetic rats administered with oryzanol (50 and 100 mg/kg) and diabetic rats administered with standard glibenclamide (10 mg/kg) orally. Following 8 weeks of streptozotocin injection and respective treatments, fasting blood glucose, biochemical markers of renal function and renal oxidative stress were evaluated in serum, urine and kidney tissue, together with histopathological assessment. The results revealed that treatment with oryzanol significantly improved the glycemic status and renal function in diabetic rats with respect to marked normalization on the levels of creatinine, uric acid, blood urea nitrogen, albumin, urinary albumin:creatinine ratio, kidney tissue enzyme, total protein, serum lipid profile and electrolyte concentrations in a dose-dependent manner. Further, oryzanol supplementation revealed a considerable dose-dependent improvement in superoxide dismutase and catalase activities and reduced glutathione levels, with a significant decline in the extent of lipid peroxidation in diabetic kidneys. Histopathological observations also evidenced regression in renal pathological alterations with oryzanol. Therefore, oryzanol confers marked protection against functional and morphologic injuries in the kidneys of diabetic rats by modulating renal alterations, improving serum lipid profile and attenuating the markers of oxidative and/or nitrosative stress in renal tissues.

Histopathological Study of Evening Primrose Oil Effects on Experimental Diabetic Neuropathy

Diabetic polyneuropathy is a serious complication of diabetes mellitus and the most frequent neuropathy worldwide. Aim: This study was designed to investigate the possible beneficial effects of evening primrose oil (EPO) on histopathological changes of sciatic nerves in streptozotocin-induced diabetic rats. Materials and methods: The rats were randomly allotted into three experimental groups: A (control), B (diabetic untreated), and C (diabetic treated with EPO); each group contained 10 animals. Groups B and C received streptozotocin (STZ) to induce diabetes. The rats in group C were given EPO for 2 weeks after 6 weeks of STZ injection. Blood and tissue samples were obtained for biochemical and histopathological investigation. Results: STZ-treated diabetic rats showed reduction of the size of islets of Langerhans, fatty degeneration in the pancreatic acini with dilation, irregularity, and increased thickness of blood vessels. Electron micrography of sciatic nerves of diabetic rats showed multiple vaculations and partial separation of myelinated nerve fibers with axonal atrophy, endoneural edema, and increased collagen fibers. Compared with diabetic rats, EPO induced partial recovery from diabetes-induced pancreatic and nerve damage. Conclusions: Histologic evaluation of the tissues in diabetic animals treated with EPO showed fewer morphologic alterations with significant decrease of myelin breakdown. Furthermore, the ultrastructural features of axons showed partial improvement. It is believed that further preclinical research into the utility of EPO may indicate its usefulness as a potential treatment on peripheral neuropathy in STZ-induced diabetic rats.

Protective Effect and Potential Mechanism of Ginkgo biloba Extract EGb 761 on STZ‐induced Neuropathic Pain in Rats

Diabetes induced neuropathic pain is recognized as one of the most difficult types of pain to treat with conventional analgaesics. EGb 761 is a standardized extract of Ginkgo biloba that has analgaesic and antiinflammatory properties and modulatory effects on key pain-related molecules. We examined the effect of EGb 761 on streptozotocin (STZ)-induced neuropathic pain behaviours and assessed its mechanism of action. Streptozotocin (20 mg/kg i.p for 5 days) was administered to induce experimental diabetes. Pain hypersensitivity to radiant heat was measured using the Dynamic Plantar Aesthesiometer to test the pain threshold. Diabetic rats exhibited mechanical allodynia and thermal hyperanalgaesia after the third week of STZ injection and concomitantly increased thiobarbituric acid reactive substance and nitric oxide concentration. The antioxidant enzymes level of superoxide dismutase and catalase was markedly reduced in STZ-diabetic rats (p < 0.05). Systemic administration of EGb 761 (25, 50 and 100 mg/kg), starting after the third week following STZ injection, dose-dependently reversed STZ-induced thermal hyperanalgaesia and mechanical allodynia. Moreover, it reduced oxidonitrosative stress and concomitantly restored the level of antioxidant enzymes (p < 0.05) as compared with untreated diabetic rats. These results suggest that EGb 761 attenuated STZ-induced neuropathic pain behaviours by inhibiting oxidative and nitrosative stress and may constitute a new approach for treatment of painful diabetic neuropathy.