Treatment Of Diabetic Rats Research Articles

AMELIORATING THE METABOLIC DISORDER IN STREPTOZOTOCIN-INDUCED DIABETIC RATS BY HAEMATOCOCCUS PLUVIALIS EXTRACT

Objective: The purpose of the current study is to evaluate the antidiabetic influence of Haematococcus pluvialis (H. pluvialis) ethanolic extract on streptozotocin (STZ)-induced rats.Methods: This influence was assessed by measuring; asymmetric dimethylarginine (ADMA), von willebrand factor (vWf), 15-lipoxygenase (15-LOX), 5-lipoxygenase (5-LOX), epidermal growth factor (EGF) and lipoxin-A4 (LXA4). The histopathological examinations of cardiac and renal tissues were also performed.Results: The presented results showed an elevation in the levels of ADMA, vWf, 15-LOXand 5-LOX with percentage increase 430.30, 77.54, 61.05 and 81.09 %, respectively in diabetic rats. However, the EGF and LXA4 levels were decreased significantly (44.17 and51.94%, respectively) compared to normal control rats. On the other hand, treatment of diabetic rats with H. pluvialis improved ADMA, vWf, 15-LOX, 5LOX, EGF and LXA4 levels with amelioration percentages; 269.69, 54.77, 55.78, 72.68, 53.39 and 56.58%, respectively. Additionally, the histopathological examination of diabetic cardiac tissue revealed congestion of myocardial blood vessel, vacuolation of the sarcoplasm of cardiac myocytes and focal necrosis of myocytes associated with inflammatory cells infiltration. Beside, vacuolation of epithelial lining of renal tubules and endothelial lining glomerular tuft as well as cystic dilatation of renal tubules were detected. However, cardiac tissue and renal tubules of diabetic rats treated with H. pluvialis ethanolic extract (150 mg/kg b.wt.) showed normal cardiac myocytes, vacuolation of epithelial lining renal tubules and endothelial lining glomerular tuft, congestion of glomerular tuft and intertubular renal blood vessels.Conclusion: These results confirmed the improving role of H. pluvialis in controlling type 2diabetes.

Protective effect of hydroalcoholic extract of Teucrium polium on diabetes-induced testicular damage and serum testosterone concentration

Diabetes has an adverse effect on spermatogenesis by rising oxidative stress. The aim of this study was to investigate the effect of Teucrium Polium extract administration on spermatogenesis and testicular structure in diabetic rats induced with Streptozotocin. 32 male Wistar rats were randomly divided into four groups (n=8/each): control group, diabetic group received distilled water, and two experimental groups included diabetic rats treated with 50 and 100 mg/body weigh of Teucrium Polium extract for 6 six weeks. After six weeks, the left testis had been removed and the morphometrical study was performed. Blood samples were collected from the ophthalmic veins of the rats and plasma levels of glucose and testosterone hormone were measured afterward. The reduction in diameters of the seminiferous tubules and thickening of the wall of the seminiferous tubules (p=0.05) were seen in diabetic rats. Also, the degenerative changes in cells arrangement have been observed. Statistical analysis showed the use of Teucrium Polium significantly improved the above disorders in treatment group (100 mg/BW) in contrast to the non treated diabetic group (p=0.05), but no significant difference was seen between the experimental group treated with 50 mg/BW of Teucrium polium and diabetic group (p=0.08). These data also revealed that treatment of diabetic rats with 100 mg/BW of Teucrium Polium extract significantly improves the change in serum glucose (p=0.001) and testosterone (p=0.03). The results of the present study indicate that diabetes produces degenerative changes in the testis of rats and administration of Teucrium polium reduces complications resulted from diabetes.

Oleanolic acid protects against diabetic cardiomyopathy via modulation of the nuclear factor erythroid 2 and insulin signaling pathways.

Oleanolic acid (OL) is a pentacyclic triterpene compound used for the treatment of hepatitis, liver fibrosis and liver cirrhosis. In China, there is no published research on the effect or biological utilization of OL on liver diseases. The aim of the present study was to investigate the protective effects of OL against diabetic cardiomyopathy and its possible mechanism. A rat model of diabetes was established using streptozotocin and the effect of OL on diabetic cardiomyopathy (DCM) was evaluated. The results demonstrated that OL significantly reversed the DCM-induced changes to body weight, heart rate, echocardiography and hemodynamics, phosphorylated-glycogen synthase (GS) and glycogen phosphorylase (GP) activity in diabetic rats (all P<0.01). Treatment of diabetic rats with OL significantly inhibited oxidative stress and activated heme oxygenase (HO)-1/nuclear factor erythroid 2 (Nrf2) signaling in a rat model of diabetes (both P<0.01). The results of the present study indicate that OL protects against DCM through the HO-1/Nrf2 and insulin modulating GS/GP signaling pathways.

ANTIDIABETIC ACTIVITY OF CALOTROPIS GIGANTEA WHITE FLOWER EXTRACTS IN ALLOXAN INDUCED DIABETIC RATS

Calotropis gigantea white (Asclepiadaceae) has been documented as a traditional treatment of diabetes. The aim of this study was to evaluate the antidiabetic activity of chloroform and ethyl acetate extracts from the flower in normal and alloxan-induced diabetic rats. Blood samples were obtained and blood glucose levels were analyzed employing a glucometer at different time intervals on 1st, 4th, 8th and 12th day of the treatment with C. gigantea white extracts compare to glibenclamide (10 mg / kg). From the results, it is revealed that the test chloroform, and ethyl acetate extracts at a dose level 500 mg / kg, showed a significant reduction in blood sugar level day in a progressive manner comparable to glibenclamide. Biochemical parameters, including hemoglobin, urea, creatinine, serum cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were also assessed. Treatment of diabetic rats with the two extracts of this plant restored the elevated biochemical parameters significantly (p<0.05) to the normal level. It also proves the traditional claim with regard to C. gigantea white for its anti-diabetic activity. Keywords: Calotropis gigantea white flowers, antidiabetic activity, alloxan, lipid profile.

English

Hibiscus is commonly used traditionally for the treatment of some diseases such as hypertension and as antidiabetic herbal medicine. The objective of the present study is to investigate the effect of the oral administration of aqueous methanolic extract of Hibiscus rosa-sinensis leaves (400 mg/Kg) on streptozotocin (STZ) induced diabetic rats and alteration in liver and kidney functions. The treatment of diabetic rats with hibiscus leaves extract reduced levels of plasma glucose, cholesterol, aspartate aminotransferase (AST), alanine aminotransferase (ALT), uric acid and creatinine and hepatic malondialdehyde that was elevated in diabetic rats. Moreover, the Hibiscus leaves extract mitigates the decrease in hepatic superoxide dismutase and plasma protein levels due to STZ injection. The treatment of rats with STZ only results in some pathological effects in liver and kidneys as degeneration in most of hepatocyte and glomeruli. The extract of H. rosa-sinensis leaves reduced the pathological changes. The treatment of diabetic rats with Hibiscus extract was shown to have hepatic and renal protective effects in diabetic rats induced experimentally. Here, two compounds, that is, orientin (Luteolin-8-C-glucoside) and verbascoside (phenylpropanoids glycoside) were isolated from H. rosa-sinsensis. The two compounds were identified by spectral analysis (UV, 1H and 13C-NMR). These results clearly indicate that aqueous leaves extract of H. rosa-sinensis possess antidiabetic and hypolipidemic effects in diabetic rats which may be due to antioxidant properties of the hibiscus extract. Key words: Hibiscus rosa-sinensis, hypoglycemic, antioxidant, orientin, verbascoside.

Treatment with Captopril Enhances the Vascular Relaxation Induced by the Angiotensin II Type 2 Receptor (AT2R) Agonist CGP42112 in Diabetic Rats

The role of the AT2 receptor (AT2R) in physiological and pathophysiological processes is still controversial. Some studies suggest that expression of AT2R increases in certain diseases like diabetes mellitus. This could have beneficial effects as signaling through the AT2 receptor has been shown to counter the effects of angiotensin II mediated through the AT1 receptor, which are believed to contribute to pathological changes; this is supported by the favorable effects of ACE inhibitors and Angiotensin receptor blockers on the course of diabetes induced complications in renal function. We examined the effect of diabetes and of treatment with captopril on the vascular responses to CGP42112 (CGP), an AT2R selective agonist, in Sprague Dawley rats with streptozotocin (85 mg/kg i.v.) induced diabetes. Rats were followed for either 2, 4 or 12 weeks, at the end of which period thoracic aortas were isolated and used for measurement of relaxant responses to CGP42112 after pre‐contraction with phenylephrine. In a subset of the 4‐week study, osmotic pumps were implanted at week 2 to deliver either captopril (50 mg/kg/day) or losartan (5 mg/kg/day) s.c. for 2 weeks. All aortic ring studies were conducted in the presence of losartan (100 μM) to prevent interactions of CGP with the AT1R. CGP induced a mild (10%) relaxation in aortic rings at 2 weeks, 4 weeks and 12 weeks in the control animals. The response to CGP in aortic rings from diabetic rats was not different from controls. Treatment with losartan for 2 weeks did not alter the responses to CGP observed after 4 weeks. However, treatment with captopril for 2 weeks resulted in a markedly exaggerated relaxant response to CGP reaching up to 50% relaxation. These preliminary results suggest that while diabetes, per se, may not alter responses to CGP, treatment of diabetic rats (but not control rats) with captopril produces a marked increase in the sensitivity of the AT2R. Considering the known anti‐proliferative and anti‐ischemic effects of AT2R activation, these results potentially imply that the use of ACE inhibitors together with AT2R agonists could amplify the protective effect of ACE inhibitors against diabetes induced complications. Thus, the pathophysiological and therapeutic implications of this finding require further study.Support or Funding InformationSupported by funds from the Medical Practice Plan, AUB Faculty of Medicine

Impaired Corneal Sensation and Nerve Loss in a Type 2 Rat Model of Chronic Diabetes Is Reversible With Combination Therapy of Menhaden Oil, α-Lipoic Acid, and Enalapril.

This study investigated the efficacy of monotherapy versus combination of menhaden oil, α-lipoic acid, and enalapril on corneal sensation and morphometry and other neuropathy-related endpoints in a rat model of type 2 diabetes. Male Sprague-Dawley rats (aged 12 weeks) were fed a high-fat diet for 8 weeks followed by 30 mg/kg streptozotocin. After 16 weeks of hyperglycemia, 12-week treatments consisting of menhaden oil, α-lipoic acid, enalapril, or their combination were initiated. Before and after treatments, we performed analyses of multiple neural and vascular endpoints including corneal sensitivity, corneal nerve density, vascular reactivity of epineurial arterioles, motor and sensory nerve conduction velocity, intraepidermal nerve fiber density, and thermal nociception. Before treatment, all the neural and vascular endpoints in diabetic rats were impaired. Treating diabetic rats with monotherapy was effective in improving neural and vascular deficits with menhaden oil being most efficacious. However, the combination therapy provided the greatest benefit and improved/reversed all nerve and vascular deficits. The effect of combination therapy on corneal relative sensitivity and structure (in mm/mm), primary endpoints for this study, for control, diabetic, and diabetic treated rats was 4.2 ± 1.4 and 7.5 ± 0.5, 12.1 ± 1.3* and 3.8 ± 0.2*, and 6.6 ± 2.3 and 7.3 ± 0.5, respectively (*P < 0.05 compared with control rats; P < 0.05 compared with diabetic rats). These studies suggest that a combination therapeutic approach may be most effective for treating vascular and neural complications of type 2 diabetes.

Therapeutic efficacy of neural stem cells originating from umbilical cord-derived mesenchymal stem cells in diabetic retinopathy

The aim of this study was to evaluate the effects of intravitreal injection of neural stem cells (NSCs) originating from human umbilical cord-derived mesenchymal stem cells (UC-MSCs) on neurodegeneration of diabetic retinopathy (DR) in rats. UC-MSCs were isolated and passaged, followed by induction to NSCs in neural differentiation medium. Four weeks following NSC transplantation, treatment attenuated retinal vascular dysfunction compared with non-treated rats, and BDNF and Thy-1 expression was significantly higher in the treated group than in the control group. Treatment of diabetic rats with NSCs prevented the decrease in BDNF levels caused by diabetes. The average leakage of Evans Blue (EB) dye in the treated group was significantly less than that in the control group. These morphological improvements were accompanied by a restoration of vision, as documented by F-ERG. NSCs originating from MSCs demonstrated a neuroprotective effect by increasing the number of surviving RGCs and significantly reducing the progression of DR. Thus, transplantation of NSCs could be a novel strategy for the treatment of neurodegeneration in DR.

1Biochemistry Department, Faculty of Vet. Med. Benha Univ., Egypt.

The present study was to determine the effect of aged garlic extract (AGE) on alleviating diabetic cardiomyopathy (DCM)in rats. An experimental diabetic rat model was induced by a single dose (60mg/kg body weight) of I.P injection ofstreptozoticin (STZ). AGE was orally administrated at a dose of 500 mg/kg body weight. Metabolic profiles include serumglucose, insulin, total cholesterol and triacylglycerols and myocardial enzymes activities as creatine kinase-isoenzyme(CK-MB), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) were determined. The obtained resultsindicated that administration of AGE increased the body weight and insulin concentration, meanwhile, significantdecrease in serum glucose concentration, CK-MB and LDH activities when compared with untreated induced diabeticgroup. Total cholesterol, triacylglycerols and AST showed non-significant changes in serum values in AGE treateddiabetic rats in comparing with STZ-induced diabetic group. From the obtained results it could be concluded that, AGEhas great potential therapeutic effect in the diabetic cardiomyopathy and other complications of coronary heart disease

Neuroprotective effects of octreotide on diabetic neuropathy in rats.

The purpose of the present study is to investigate the possible healing effects of octreotide (OCT) on motor performance, electrophysiological and histopathological findings of diabetic neuropathy in a rat model of diabetes mellitus (DM). To induce diabetes, rats were administered a single dose (60mg/kg) of streptozotocin (STZ). Diabetic rats were treated either with saline (1ml/kg/day, n=7) or OCT (0.1mg/kg/day, n=7) for four weeks. Seven rats served as control group and received no treatment. At the end of the study, electromyography (EMG), gross motor function (inclined plate test), general histology and the perineural thickness of sciatic nerve were evaluated. At the end of study, weight loss was significantly lower in OCT treated rats than that of saline treated ones (p<0.001). Electrophysiologically, compound muscle action potential (CMAP) amplitudes of the saline treated DM group were significantly reduced than those of controls (p<0.0001). Also, distal latency and CMAP durations were significantly prolonged in saline treated DM group (p<0.05) compared to control. However, treatment of diabetic rats with OCT significantly counteracted these alterations in EMG. Furthermore, OCT significantly improved the motor performance scores in diabetic rats (p<0.05). Histomorphometric assessment of the sciatic nerve demonstrated a significant reduction in perineural thickness in OCT treated group compared to saline group. In conclusion, OCT possesses beneficial effects against STZ-induced diabetic neuropathy, which promisingly support the use of OCT as a neuroprotective agent in patients with diabetic neuropathy.

Antidiabetic and Antioxidant Potentials of Amaranthus hybridus in Streptozotocin-Induced Diabetic Rats

ABSTRACTContext: Amaranthus hybridus (Amaranthaceae) has been used as a folk medicine in southern parts of India for the treatment of diabetes. Objective: This research evaluates the antidiabetic and antioxidant effects of Amaranthus hybridus ethanol leaf extract (AHELE) in streptozotocin-induced diabetic rats. Methods: Blood glucose levels of diabetic rats were measured on days 1, 4, 7, and 15 after oral administration of AHELE at doses of 200 and 400 mg/kg for 14 days. The effects of extract were observed on serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, serum alkaline phosphatase, cholesterol, high- and low-density lipoprotein, antioxidant potential, and histopathological changes. Result: AHELE (200 and 400 mg/kg) caused a significant (p < 0.001) reduction in blood glucose levels on day 15 (152.2 and 181.2 mg/dL, respectively versus diabetic control 287.0 mg/dL). The extract also improved serum biochemical parameters associated with diabetes. A significant (p < 0.001) decrease in malondialdehyde protein (liver: 15.92, 12.29 nmol/mg, and kidney: 13.92, 10.29 nmol/mg vs. diabetic control 25.49, 24.49 nmol/mg), increase in superoxide dismutase protein (14.01; 17.47 IU/mg, and 25.01; 37.47 IU/mg vs. diabetic control 9.65; 15.65 IU/mg), catalase protein (35.80, 44.49, and 39.80, 49.69 nmol/min/mg vs. diabetic control 18.45, 20.85 nmol/min/mg) and reduced glutathione protein (44.77, 55.08 and 40.77, 51.08 μM/gm vs. diabetic control 29.81, 26.50 μM/gm) were observed. Conclusions: The study reveals that treatment of diabetic rats with AHELE significantly reduced hyperglycemia-associated oxidative damage. This could provide a rationale for the use of the plant to treat diabetes in folk medicine.

Modulatory effect of vanillic acid on antioxidant status in high fat diet-induced changes in diabetic hypertensive rats.

The worldwide incidence of diabetes has increased dramatically along with widespread lifestyle and dietary changes. Diets high in fat are strongly associated with the development of obesity and can induce insulin resistance in humans and animals. It is clear that obesity constitutes a risk factor for contributing to the development of type 2 diabetes. In the present study, we investigated the therapeutic potential action of vanillic acid on diabetes associated complications using a rat model. Rats were made diabetic hypertensive by high fat diet (HFD) for 20 weeks and were treated with vanillic acid (50mg/kg bw) for last 8 weeks. The effects of vanillic acid on glucose, plasma insulin, systolic and diastolic blood pressure, thiobarbituric acid reactive substances (TBARS), hydroperoxides as a lipid peroxidation marker, and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), vitamin C and vitamin E as an antioxidant marker, AST and ALT as a liver function marker, urea, uric acid and creatinine as a kidney function marker were investigated. Histopathology of liver and kidney was also investigated as part of the pathology of diabetes. Treatment of diabetic rats with oral administration of vanillic acid at a dose of 50mgkg/body weight for 8 weeks resulted in a significant decrease in fasting plasma glucose, insulin and blood pressure levels in comparison with diabetic control group. The antioxidant activities were significantly increased and the levels of lipid peroxidation markers were significantly decreased in diabetic hypertensive rats treated with vanillic acid. These results suggest that vanillic acid offer a modulatory effect on control of diabetic hypertension by reduction of blood glucose, insulin and blood pressure, combating oxidative stress by activation of tissue antioxidants.

Gallic acid improves endothelium-dependent vasodilatory response to histamine in the mesenteric vascular bed of diabetic rats.

Endothelial dysfunction is one of the many complications caused by diabetes mellitus. The aim of the present study was to evaluate the effects of gallic acid (GA) on the mesenteric vascular bed (MVB) response to histamine in diabetic rats. Forty male Wistar rats were randomly assigned to a control group, an untreated alloxan-induced diabetic group and three diabetic groups treated with different doses of GA. Six weeks after induction of diabetes and GA treatment, total antioxidant capacity (TAC), malondialdehyde (MDA) concentrations, and the vasodilatory response to histamine of the MVB (measured as changes in perfusion pressure) were determined. The vasodilatory response to histamine and TAC decreased, whereas MDA increased in the plasma from diabetic rats (P < 0.01). However, in the presence of 3 × 10-5 mol/L N G -nitro-l-arginine methyl ester (a nitric oxide synthase inhibitor) and 1 × 10-5 mol/L indomethacin (an inhibitor of prostaglandin production), the vasodilatory response of the MVB to histamine was reduced in all groups (P < 0.001). Treatment of diabetic rats with 20 and 40 mg/kg per day GA, but not 10 mg/kg per day GA, increased TAC and decreased MDA concentrations (P < 0.01 and P < 0.001 vs untreated diabetic rats, respectively) and significantly improved the vasodilatory response to histamine (P < 0.05 and P < 0.001, respectively). The results show that, in diabetic rats, the endothelium-dependent vasodilatory response of the MVB to histamine is significantly decreased and depends on both nitric oxide- and prostaglandin-producing pathways and may be mediated by oxidative stress. Treatment with the antioxidant GA restored the vasodilatory response of the MVB to histamine.

Potent antihyperglycemic and hypoglycemic effect of Tamarix articulata Vahl. in normal and streptozotocin-induced diabetic rats.

The purpose of this study was to investigate the effect of a single dose and daily oral administration for seven days of the aerial part aqueous extract (A.P.A.E) of Tamarix articulata Vahl. (T. articulata) (5mg/kg) on blood glucose levels in both normal and streptozotocin-induced diabetic rats (STZ). Single oral administration of T. articulata A.P.A.E reduced blood glucose levels 6h after administration in normal rats (p<0.0001) and STZ diabetic rats (p<0.001). Furthermore, blood glucose levels were decreased in both normal (p<0.05) and STZ diabetic rats (p<0.0001) after seven days of treatment. Moreover, no significant changes in body weight in normal and STZ rats were shown. According to the oral glucose tolerance test, the aqueous extract of T. articulata (5mg/kg) was shown to prevent significantly the increase on blood glucose levels in both normal and diabetic treated rats 30min, 60min and 120min after glucose administration when compared to the control group. Additionally, histopathological analysis revealed the beneficial effect of T. articulata on pancreas and liver. Finally, the antioxydant activity of the aqueous extract of Tamarix articulata was evaluated by the method of trapping of free radical 2,2-diphenyl-1 picrylhydrazyl (DPPH). Tamarix articulata revealed inhibitory concentrations of 50% of free radicals (IC50) of 203.15μg/ml. In contrast, the synthetic antioxidant butylhydroxytoluene (BHT) has showed an IC50 equal to 13.71μg/ml. In conclusion, this study demonstrates antihyperglycemic, hypoglycemic and antioxidant effects of T. articulata in severe diabetic state thus warrants further investigation on its major compounds as well as mechanistic studies.

Hepatoprotective, Antihyperlipidemic, and Anti-inflammatory Activity of Moringa oleifera in Diabetic-induced Damage in Male Wistar Rats.

Background:The number of individuals with diabetes is increasing daily, and diabetes is presently estimated to affect about 422 million adults worldwide. Conventional drugs used to treat diabetes are not without severe side effects, accessibility, and affordability. This study elucidates the potential effects of Moringa oleifera (MO) leaves extract to manage and treat diabetes induced in male Wistar rats.Materials and Methods:Adult male Wistar rats were randomly divided into four groups (n = 12/group): NC – nondiabetic rats (positive control), MO – nondiabetic-treated rats, DM – diabetic rats (negative control), DM + MO – diabetic-treated rats. Hepatic enzymes and biochemical parameters as well as antioxidant capacity and inflammatory cytokine levels were assessed. Levels of low-density lipoprotein, high-density lipoprotein, and total cholesterol were evaluated.Results:Oral administration of methanolic extract of MO (250 mg/kg) to diabetic rats for 42 days showed a significant reduction in hepatic enzyme markers and normalized lipid profile parameters in the serum compared to normal control group. Treatment also increased the level of antioxidant capacity and alleviated inflammatory biomarkers of the liver. Histology sections of the liver tissue showed protective effect of MO in treated rats.Conclusions:MO showed hepatoprotective, anti-inflammatory, and lipid-lowering effects against streptozotocin-induced hepatotoxicity. Histological section demonstrated specific alterations in the liver of the diabetic and nondiabetic male Wistar rats while MO treatment revealed improvement in liver alterations.Abbreviations Used: IL 1: Interleukin 1, IL 6: Interleukin 16, MCP-1: Monocyte chemotactic protein, TNF-α: Tumor Necrotic factor alpha, ROS: Reactive oxygen species, MO: Moringa oleifera, STZ: Streptozotocin, SRC: Standard rat chow, ALP: Alkaline phosphatase, AST: Aspartate aminotransferase, ALT: Alanine aminotransferase, ORAC: Oxygen radical absorbance capacity, LDL: Low density lipoprotein, HDL: High density lipoprotein, CHOL: Total cholesterol.

Rheum turkestanicum rhizomes possess anti-hypertriglyceridemic, but not hypoglycemic or hepatoprotective effect in experimental diabetes.

Rheum turkestanicum (R. turkestanicum) rhizomes have been used in Iranain traditional medicine as an anti-diabetic agent. The purpose of the present investigation was to evaluate the anti-diabetic and antioxidant activities of R. turkestanicum rhizome extract in streptozotocin-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of 55 mg/kg streptozotocin in male Wistar rats. Diabetic rats received the decoction extract of R. turkestanicum rhizomes at the doses of 200, 400 and 600 mg/kg daily by gavage for 3 weeks. Serum glucose and lipid levels were measured in all groups before diabetes induction and at the end of week 3. Oxidative stress was evaluated in the liver by measurement of malondialdehyde levels and total thiol concentration at the end of the experiment. A significant increase in serum glucose and triglyceride levels was observed in diabetic rats, which was accompanied by increased malondialdehyde levels and decreased total thiol concentration in the liver after 3 weeks. Treatment of diabetic rats with R. turkestanicum rhizome extract at the doses of 200, 400 and 600 mg/kg over a 3-week period did not change serum glucose, hepatic malondialdehyde and total thiol levels in diabetic rats. However, treatment with R. turkestanicum extract significantly decreased serum triglyceride levels in a dose-dependent manner at the end of the experiment. R. turkestanicum rhizome extract possess anti-hypertriglyceridemic, but not hypoglycemic or hepatoprotective effect in diabetic rats. Therefore, R. turkestanicum rhizome should be consumed with more caution by diabetic patients.

Calcium Dobesilate Is Protective against Inflammation and Oxidative/Nitrosative Stress in the Retina of a Type 1 Diabetic Rat Model

Calcium dobesilate (CaD) has been prescribed to some patients in the early stages of diabetic retinopathy to delay its progression. We previously reported that the treatment of diabetic animals (4 weeks of diabetes) with CaD, during the last 10 days of diabetes, prevents blood-retinal barrier breakdown. Here, we aimed to investigate whether later treatment of diabetic rats with CaD would reverse inflammatory processes in the retina. Diabetes was induced with streptozotocin, and 6 weeks after diabetes onset, CaD (100 mg/kg/day) was administered for 2 weeks. The treatment with CaD significantly increased glial fibrillary acidic protein (GFAP) levels in the retina of nondiabetic animals (138.6 ± 12.8% of control) and enhanced the diabetes-induced increase in GFAP levels (174.8 ± 5.6% of control). In addition, CaD prevented the increase in mRNA and protein expression of tumor necrosis factor and interleukin-1β, as well as the formation of oxidized carbonyl residues and the increase in nitrotyrosine immunoreactivity, particularly in the ganglion cell layer of diabetic animals. We demonstrate that the treatment of diabetic animals with CaD can reverse the established proinflammatory processes in the retina. These beneficial effects appear to be attributed, at least partially, to the antioxidant properties of CaD.

THE EFFECT OF TESTOSTERONE AND VOLUNTARY EXERCISE, ALONE OR TOGETHER, ON miRNA-126 EXPRESSION CHANGES IN HEART OF DIABETIC RATS.

Ninety Wistar male rats were used in this study. Type 1 diabetes was induced by i.p injection of 50 mg/kg of streptozotocin in all animals. After 42 days of treatment with testosterone (2mg/kg/day) or voluntary exercise alone or in combination, the heart of the rats has been removed and MicroRNA was extracted from the heart using miRCURYTM RNA isolation kit. Our results showed that either testosterone or exercise increased miRNA-126 expression levels in the heart of diabetic rats. Treatment of diabetic rats with testosterone and exercise at the same time had a synergistic effect on miRNA-126 levels in the heart. Furthermore, in castrated diabetes group, miRNA-126 levels were significantly decreased in heart, whereas either testosterone treatment or exercise training enhanced expression of this miRNA. Also, simultaneous treatment of castrated diabetic rats with testosterone and exercise had an additive effect on miRNA-126 expression levels. This study showed that testosterone and exercise promote an increase in the expression of miRNA-126 in the heart tissue and this may be related to cardiac angiogenesis. These results may indicate that testosterone and exercise can help to prevent progression of diabetic cardiomyopathy due to impaired angiogenesis in the heart.

Evaluation of Antidiabetic Activity of Aqueous and Etylic alcohol Extracts of Stem Bark of Xylopia villosa Chipp (Annonaceae)

This study aims to evaluate antidiabetic activity of aqueous and ethanolic extracts of Xylopia villosa stem bark. Induction of diabetes was made with Streptozocin on male rats. Treatments of diabetic rats with aqueous and ethanolic extracts of Xylopia villosa at doses of 100 and 200 mg / kg bw and Daonil (the reference molecule) at doses of 10 and 20 mg / kg bw revealed that ethanolic extract (200 mg / kg) bw behaved like Daonil (20 mg / kg bw). It is the therapeutic dose needed to correct hyperglycaemia. At this dose, the ethanolic extract allowed an important insulin secretion equivalent to the non-diabetic control rats and allowed the gradual reconstitution of the islets of Langerhans and the reappearance of the β cells responsible for the secretion of the insulin. This situation would be linked to the flavonoids and zinc contained in the extracts. Indeed, Zinc, in addition to being a powerful antioxidant, would have a protective insulin action and an important insulin-like effect by activating the kinases involved in insulin signaling and the phosphorylations necessary for insulin efficacy. Also, flavonoids improve the sensitivity of the body's cells to insulin, which reduces the incidence of type 2 diabetes.

Can allopurinol improve retinopathy in diabetic rats? Oxidative stress or uric acid; which one is the culprit?

Allopurinol, an inhibitor of xanthine oxidase, reduces both plasma uric acid and oxidative stress and shows useful effects on some complications of diabetes. However, it is not defined which of the above mentioned properties are involved. Moreover, to the best of our knowledge no study has been done on the effects of allopurinol on diabetic retinopathy. In the present study, the effect of allopurinol on experimental diabetic retinopathy and its possible mechanism has been investigated. Thirty two rats were divided into four groups of eight rats each; (1) normal, (2) diabetic control, (3) diabetic + allopurinol (50 mg/kg.day), (4) diabetic + benzbromarone (10 mg/kg.day). Drugs were administered daily and orally from the day after diabetes induction for eight weeks. Thereafter retinal function and structure were evaluated by electroretinography and microscopic studies. Uric acid and oxidative stress biomarkers were measured biochemically. Diabetes significantly increased plasma uric acid and oxidative stress markers and reduced body weight and amplitude of electroretinogram (ERG) b-wave and oscillatory potentials. Treatment of diabetic rats with allopurinol caused a significant increase in the amplitude of ERG b-wave (87%) and decrease in blood sugar (20%), uric acid (49%), and 8-iso-prostaglandin F2a (56%), but had no effect on the number of retinal ganglionic cells and oscillatory potentials. Benzbromarone showed no significant effects on the considered parameters except the reduction of uric acid. Allopurinol improved the b-wave amplitude of diabetic rats. It seems that this beneficial effect is due to the reduction of oxidative stress rather than its effect on plasma uric acid.