Alloxan-induced Diabetic Rabbits Research Articles

Effects of Aqueous Extract of Triplochiton scleroxylon on White Blood Cell Differentials in Alloxan-Induced Diabetic Rabbits

6 Abstract: Studies were conducted on the effects of aqueous extract of Triplochiton scleroxylon on white blood cell differentials in alloxan-induced diabetic rabbits. At least 100 mL of the aqueous extract was administered orally to test rabbits of New Zealand strain weighing between 1200 to 1680g for a period of 28 days. Clean drinking troughs were used in the administration of water and aqueous extract to the control and test rabbits respectively. Blood was collected for analyses intravenously through the larger vein at the back of the ear of rabbits. Hematological Swelab autocounter 920 (UK) was used in the determination of white blood cell E+ differentials; neutrophils, lymphocytes, basophils and eosinophils. Analyses of results showed that the aqueous extract of the bark of Triplochiton scleroxylon did not have significant effects (p>0.05) on white blood cell differentials in alloxan-induc ed diabetic rabbits studied. Plasma glucose concentration decreased significantly (p<0.05) on the 18th, 24th and 28th days of administration of aqueous bark extract of this plant. Triplochiton scleroxylon has hypoglycemic and anti-diabetic properties and the aqueous bark extract may not predispose to white blood cell dysfunctions.

Assessment of Wound Healing in the Alloxan-Induced Diabetic Rabbit Ear Model

The enhancement of diabetic wound healing represents a major clinical challenge to researchers. The challenge faced is to identify a suitable animal model that best represents the human situation. However, the majority of diabetic wound healing models are in rodents and are hindered by rapid contraction and thus do not reflect epithelial cell migration, as seen in the human wound. The alloxan-induced diabetic rabbit model is a cheap, reproducible model and offers the advantage of providing a noncontractile avascular wound bed. This study aimed to compare the effects of acute hyperglycemia in the alloxan model to normal rabbit controls on wound healing, using methods of stereology. Alloxan was administered 7 days prior to surgery. Four full-thickness punch biopsy wounds were created on each ear (n = 4). Wounds were excised at 7 and 14 days and prepared for stereological analysis from Masson's trichrome-stained histological sections. It was noted that the alloxan-treated animals showed an increase in the number of inflammatory cells and fibroblasts at 14 days. In addition, it was noted that the length density of blood vessels was reduced in the alloxan-induced diabetic rabbits, representing a greater radial diffusion distance between vessels and a less efficient network for nutrient exchange. This is the first study to take a stereological approach to defining the effects of diabetes mellitus on wound healing in a noncontractile model.

Oxidative stress in the testis of hyperglycemic rabbits treated with repaglinide

AbstractIn the present study, the induction of oxidative stress was examined in the testis of alloxan-induced diabetic rabbits. In addition, the protective effect of repaglinide, an oral anti-diabetic, at a dose of 1 mg daily was studied after four and eight weeks of the treatment. For these purposes, the levels of superoxide dismutase (Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), glutathione (GSH), ascorbic acid (AA), lipid peroxidation products (LPO) and protein carbonyl groups (PCG) were quantified. Hyperglycemia resulted in significant increases in the antioxidative enzymes, Cu, Zn-SOD, CAT, GSH-Px, and GSSG-R after four and eight weeks, respectively. There was also an increase in GSH level, and a decrease in the level of AA. These effects were accompanied by an elevation in testicular LPO levels and PCG levels. Repaglinide was found to normalize the activity of GSSG-R and levels of GSH and AA, and blunted the increased lipid peroxidation, however no decrease in PCG levels were observed. In conclusion, some oxidative changes provoked in the testis of rabbits by hyperglycemia, were found to be reduced with repaglinide treatment at therapeutic dose.

In vivo assessment of antidiabetic and antioxidant activities of rosemary ( Rosmarinus officinalis) in alloxan-diabetic rabbits

Rosemary ( Rosmarinus officinalis), used in traditional Turkish folk medicine for the treatment of hyperglycaemia, is widely accepted as one of the medicinal herb with the highest antioxidant activity. Accordingly, the present study was designed to investigate the possible actions of ethanolic extract of the leaves of Rosmarinus officinalis on glucose homeostasis and antioxidant defense in rabbits. In the first set of experiments, hypoglycaemic effects of oral administration of various doses (50, 100 and 200 mg/kg) of the extract were examined in normoglycaemic and glucose-hyperglycaemic rabbits. Optimal effect was observed in both of the animal groups with a dose of 200 mg/kg of the extract and this activity was independent from the effects of insulin. In another part of experiments, acute effect of various doses of the Rosmarinus officinalis extract on blood glucose and serum insulin levels was studied in alloxan-induced diabetic rabbits. Of the three doses of extract, the highest dose (200 mg/kg) significantly lowered blood glucose level and increased serum insulin concentration in alloxan-diabetic rabbits. The last set of experiments designed to investigate the subacute effect of the Rosmarinus officinalis extract on repeated administration in alloxan-diabetic rabbits. At the doses of 100 and 200 mg/kg, antihyperglycaemic effect of extract was accompanied by a significant increase in serum insulin levels in diabetic rabbits. Furthermore, during 1 week of treatment of diabetic rabbits with a dose of 200 mg/kg of the extract showed that the extract possessed a capability to inhibit the lipid peroxidation and activate the antioxidant enzymes. It was concluded that probably, due to its potent antioxidant properties, the Rosmarinus officinalis extract exerts remarkable antidiabetogenic effect.

Investigation of the Effect of Aqeous Mistletoe Leaf Extract on Glucose and Cholesterol Levels in Alloxan-Induced Diabetic Rabbits

Aqueous leaf extract of the mistletoe was investigated for hypoglycaemic and hypocholesterolaemic effect in diabetic rabbits. Diabetes mellitus was induced in rabbits in groups I-II by a single intraperitoneal injection of alloxan monohydrate at 100mg/kg body weight. Following confirmation of hyperglycaemia, groups I and II were treated with the extract at 1.32 and 2.64g/kg body weight for three consecutive days. After the last treatment, rabbits were fasted for 12 hours and bled at 0, 2, 6 and 24 hours. Serum glucose levels were determined by the glucose oxidase method and cholesterol levels by Liebermann-Buchard method. The results showed statistically significant decreases (P 0.05), when compared to control group III. Aqueous leaf extract of the mistletoe (an epiphyte of lemon trees) may be recommended for frequent consumption in the management of insulin-dependent diabetes. Keywords : Mistletoe Extract, Glucose, Alloxan-Induced Diabetic Rabbits Journal of Medical Laboratory Sciences Vol. 14 (1) 2005: pp. 28-32

Effect of zinc on the lipid peroxidation and the antioxidant defense systems of the alloxan-induced diabetic rabbits

The effects of oral zinc supplementation on lipid peroxidation and the antioxidant defense system of alloxan (80–90 mg/kg)-induced diabetic rabbits were examined. Forty-five New Zealand male rabbits, 1 year old, weighing approximately 2.5 kg, were allocated randomly and equally as control, diabetic, and zinc-supplemented diabetic groups. After diabetes was induced, zinc-supplemented diabetic rabbits had 150 mg/L of zinc as zinc sulfate (ZnSO4) in their drinking tap water for 3 months. The feed and water consumption was higher in diabetic groups than (P<0.01) healthy rabbits. The body weight was lower in diabetic rabbits compared to control. The blood glucose levels were higher in diabetic groups than controls. The elevated plasma malondialdehyde (MDA) levels were determined in the diabetic group (P<0.01). The glutathione peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and ceruloplasmin levels in the diabetic group were decreased by the effect of diabetes but there was no difference between zinc-supplemented diabetic and control rabbits. Serum zinc concentrations were lower in diabetic rabbits but iron (Fe) and copper (Cu) levels in sera were not different among the groups. As a result, it was concluded that daily zinc supplementation could reduce the harmful effects of oxidative stress in diabetics.

Effects of in vivo antioxidant enzyme activities of myrtle oil in normoglycaemic and alloxan diabetic rabbits

In this study we aimed to evaluate the in vivo effects of myrtle oil (myrtii oleum) on the antioxidant enzymes such as superoxide dismutase and catalase, the levels of malondialdehyde in liver tissues as an index of lipid peroxidation and nitrite–nitrate levels in normoglycaemic and alloxan-induced diabetic and MO-treated rabbits. In our previous study, we assumed that MO with a dose of 50 mg/kg, possesses a hypoglycemic activity and this activity was independent from the effects of insulin. Myrtle oil exerts its hypoglycemic activity by enhanced glycolysis, glycogenesis and decreased glycogenolysis. What is more glucose load data strongly suggest that MO treatment produces hypoglycemia mainly by reducing intestinal absorption of glucose, so MO could be an α-glycosidase enzyme inhibitor which had a hypoglycaemic effect only on alloxan-induced diabetic rabbits on the fourth hour and on orally glucose loaded group. The major finding of this new study is that, MO may not offer any protection against oxidative stress during acute studies in normoglycemic and diabetic groups. Although the levels of superoxide dismutase and catalase enzyme activities did not change during acute studies in diabetes + MO group, there was a significant change at the end of 21 days. There is a very limited knowledge about MO and its effects on diabetes. Therefore, we tried to explain the mechanism that might underlie the protective effects of MO with this paper.

Effects of Aqueous Extract of Triplochiton scleroxylon on Red Blood Cells and Associated Parameters in Alloxan - Induced Diabetic Rabbits

2 Abstract: The effect of aqueous extract of Triplochiton scleroxylon on the body weight, plasma glucose concentration and some hematological parameters in alloxan-induc ed diabetic rabbits were investigated. Rabbits of the same strain (New Zealand) weighing between 1.20 and 1.68kg were used. At least 100ml of the aqueous extract of the plant was administered to a set of test rabbits for a period of 28 days. Blood was collected for analyses intravenously from the larger vein at the back of the ear of the rabbits. Plasma glucose was analyzed by spectrophotometeric method. Hematological swelab auto - counter 920 (UK) was used E+ for red blood cell counts, packed cell volume, hemoglobin and mean corpuscular hemoglobin concentration, mean corpuscular hemoglobin, mean corpuscular volume and red cell distribution width. The aqueous extract of Triplochiton scleroxylon does not have any significant effect (P>0.05) on the body weight and some hematological parameters investigated. However, plasma glucose concentration decreased significantly (P < 0.05) on the 18 , 24 and 28 days of administration of herbal extract to alloxan - induced diabetic rabbits. th th th The crude extract of this herb has an hypoglycemic properties and its use as an anti-diabetic agent may not interfere with the body weight and some hematological properties of rabbits and by extrapolation humans.

COX-2, Another Important Player in the Nitric Oxide–Endothelin Cross-Talk

See related article, pages 1439–1445 Traditionally, the role of the endothelium was thought to be primarily that of a selective barrier to the diffusion of macromolecules from the vessel lumen to the interstitial space. During the past 20 years, numerous additional roles for the endothelium have been defined such as regulation of vascular tone, modulation of inflammation, promotion as well as inhibition of vascular growth, and modulation of platelet aggregation and coagulation. Endothelial dysfunction is a characteristic feature of patients with cardiovascular risk factors such as hypercholesterolemia, hypertension, diabetes mellitus, and chronic smoking. More recent studies indicate that it may predict long-term atherosclerotic disease progression as well as cardiovascular event rate.1 There is a growing body of evidence that decreased endothelial bioavailability of nitric oxide (NO·) in particular attributable to increased production of reactive oxygen species, such as superoxide (O2·−), leads to an activation of the renin–angiotensin system,2,3 increased formation of cyclooxygenase (COX)-dependent vasoconstrictors,4 but also to increased expression of the most potent endogenous vasoconstrictor endothelin-1 (ET-1).5–9 Of the 4 active endothelins (ET-1 to ET-4) ET-1 is the predominant isoform in the cardiovascular system. ET-1 exerts its major cardiovascular effects through activation of 2 distinct G protein–coupled receptors, the ETA and ETB receptors. ETA receptors are found exclusively in smooth muscle cells. Endothelin-1 promotes vasoconstriction, mitogenesis, and thrombosis predominantly via binding to the ETA receptor. ETB receptors are localized to some extent in smooth muscle cells, but also in endothelial cells. Activation of ETB receptors has been demonstrated to cause the release of NO· and prostacyclin (PGI2).10,11 In normal states with p reserved vascular (endothelial) NO …

Effects of pioglitazone on atherogenic risk predictor indices of alloxan-induced diabetic rabbits

The effects of pioglitazone alone and in combination with either sulphonylurea or metformin on the atherogenic risk predictor indices of alloxan-induced diabetic rabbits were studied using five groups (A, B, C, D and E) of rabbits. Results of the mean values of plasma glucose, lipoproteins and atherogenic risk predictor indices determined after 4 and 8 weeks of drug administration showed that the plasma glucose, total cholesterol, LDL-cholesterol, triglycerides and VLDL levels significantly (p<0.05) decreased while HDL-cholesterol significantly (p<0.05) increased in the treated groups C, D and E when compared to group B, the diabetic control, after 4 weeks of drug administration. A greater positive effect was recorded after 8 weeks. The mean values of atherogenic risk predictor indices-- LDL-C/HDL-C and log (TG/HDL-C) after 4 and 8 weeks of drug administration were found to be significantly (p<0.05) decreased in the treated groups C, D and E when compared to group B (diabetic control) with a greater decrease also occurring after 8 weeks. The findings also showed positive synergistic effects of co-administered antidiabetic drugs like sulphonylurea and metformin on the atherogenic risk predictor indices.

Some physiological effects of a number of plant extracts in experimental diabetes rabbits

This study was designed to examine the effect of aqueous extracts Q$ Cymbopogon citratus Cardaria draba leaves and Artemisia scoparia leaves and seeds on the levels of glucose, cholesterol, triglycrides, total protein and urea in Alloxan-induced diabetic local rabbits, and The results were compared with the effect of Insulin. The effect of the aqueous extracts have been also tested on some blood parameters by measuring the number of Red Blood Corpuscles, White Blood Cells, Packed Cell Volume (PCV) and Hemoglobin. The aqueous extracts of Cymbopogon citratus and Cardaria draba produced significant decreased in glucose, cholesterol triglycrides and urea levels while significantly increased total proteins level of diabetic local rabbits, the aqueous extract of Artemisia scoparia leaves and seeds produced similar effects on the level of glucose, urea and total protein. In diabetic local rabbits the aqueous extracts of Cymbopogon citratus and Cardaria draba showed significant decrease m the number of White Blood Cells and the aqueous extract for Cardaria draba produced a significant increase in the number of Red Blood Corpuscles, whereas the aqueous extract of the Artemisia scoparia leaves and seeds produced no significant effect on the blood components. The results obtained suggest that these extracts may being used for the treatments of Diabetes Mellitus after be sure that there is no side effect.

Testosterone Restores Diabetes‐Induced Erectile Dysfunction and Sildenafil Responsiveness in Two Distinct Animal Models of Chemical Diabetes

Hypogonadism is often associated with diabetes and both conditions represent major risk factors for erectile dysfunction (ED). To investigate the role of hypogonadism on phosphodiesterase type 5 (PDE5) expression and sildenafil responsiveness in diabetes. Two different models of experimental diabetes were used: (i) alloxan-induced diabetic rabbit; and (ii) streptozotocin (STZ)-induced diabetic rat. In both experimental models, animals were separated into three groups: control, diabetic, diabetic supplemented with testosterone (T) enanthate. Rabbits were used for "in vitro" experiments. Conversely, each rats group was further subdivided: no further treatment or acute sildenafil dosing (25 mg/kg, 1 hour before "in vivo" electrical stimulation [ES]). Erectile capacity was evaluated either by "in vitro" contractility study (alloxan-induced diabetic rabbit) and "in vivo" evaluation of erectile response elicited by ES of cavernous nerve (STZ-induced diabetic rats). Also endothelial nitric oxide synthase, neural nitric oxide synthase (nNOS), and PDE5 protein (Western blot) and mRNA (quantitative real-time reverse transcriptase polymerase chain reaction [RT-PCR]) expression were measured in rat penile samples of each group. In both models, hypogonadism was observed, characterized by reduced T and atrophy of androgen-dependent accessory glands. T substitution completely reverted hypogonadism and diabetes-induced penile hyposensitivity to "in vitro" (acetylcholine, rabbit) or "in vivo" (ES, rat) relaxant stimuli, along with nNOS expression, which was reduced (P < 0.05) in STZ rats. In diabetic animals, T substitution reinstated sildenafil-induced enhancement of both "in vitro" nitric oxide donor (NCX 4040) relaxant effect (rabbit) and "in vivo" ES-induced erection (rat). PDE5 was reduced in diabetic STZ rats (P < 0.05) and normalized by T. In STZ rats, sodium nitroprusside (SNP) intracavernous injection induced a more sustained erection than in control rats, which was no further enhanced by sildenafil. T substitution normalized both hyper-responsiveness to SNP and sildenafil efficacy. In two models of diabetes T deficiency underlies biochemical alterations leading to ED. Normalizing T in diabetes restores nNOS and PDE5, and reinstates sensitivity to relaxant stimuli and responsiveness to sildenafil.

Interleukin-6 and Oxidative Stress in Plasma of Alloxan-Induced Diabetic Rabbits after Pioglitazone Treatment

There is evidence that oxidative stress might be implicated in promoting a state of systemic inflammation in diabetic patients. Understanding the role of reactive oxygen species in the inflammatory response in diabetes becomes essential in finding preventive treatments. Pioglitazone is a new oral antidiabetic agent with potent antioxidant and anti-inflammatory properties. The drug is a high affinity ligand of peroxisome proliferator-activated receptor gamma. This receptor seems to be involved in the control of inflammation by modulating the production of inflammatory mediators. In the present study, the changes in some markers of enhanced oxidative stress and in the level of pro-inflammatory interleukin-6 (IL-6) were examined in plasma of diabetic rabbits after 4 and 8 weeks of pioglitazone treatment. Ascorbic acid (AA) concentration and total antioxidant status (TAS) in plasma of diabetic animals were diminished and significantly elevated after pioglitazone treatment (p < 0.05). Protein carbonyl groups (PCG) content and IL-6 concentration were elevated in plasma of diabetic animals and significantly diminished after pioglitazone treatment. The results obtained in the present study confirm the relations of cytokine systems with oxidative stress in plasma of diabetic subjects. They also suggest the antioxidative and antinflammatory properties of pioglitazone.

Hypoglycemic and antioxidant effect of oleuropein in alloxan-diabetic rabbits

Patients with diabetes mellitus are likely to develop certain complication such as retinopathy, nephropathy and neuropathy as a result of oxidative stress and overwhelming free radicals. Treatment of diabetic patients with antioxidant may be of advantage in attenuating these complications. Oleuropein, the active constituent of olive leaf ( Olea europaea), has been endowed with many beneficial and health promoting properties mostly linked to its antioxidant activity. This study aimed to evaluate the significance of supplementation of oleuropein in reducing oxidative stress and hyperglycemia in alloxan-induced diabetic rabbits. After induction of diabetes, a significant rise in plasma and erythrocyte malondialdehyde (MDA) and blood glucose as well as alteration in enzymatic and non-enzymatic antioxidants was observed in all diabetic animals. During 16 weeks of treatment of diabetic rabbits with 20 mg/kg body weight of oleuropein the levels of MDA along with blood glucose and most of the enzymatic and non-enzymatic antioxidants were significantly restored to establish values that were not different from normal control rabbits. Untreated diabetic rabbits on the other hand demonstrated persistent alterations in the oxidative stress marker MDA, blood glucose and the antioxidant parameters. These results demonstrate that oleuropein may be of advantage in inhibiting hyperglycemia and oxidative stress induced by diabetes and suggest that administration of oleuropein may be helpful in the prevention of diabetic complications associated with oxidative stress.

Increased basal phosphorylation of detrusor smooth muscle myosin in alloxan-induced diabetic rabbit is mediated by upregulation of Rho-kinase β and CPI-17

Urinary bladder dysfunction caused by the alteration of detrusor smooth muscle (DSM) is one of the complications of diabetes. It is well established that smooth muscle contractility is regulated by an elevation of cytosolic Ca(2+) via myosin light chain (MLC) phosphorylation. However, recent studies have shown the modulation of MLC phosphorylation without a rise in Ca(2+) in smooth muscle and that two key molecules (Rho-kinase and CPI-17) are involved in the regulation of calcium sensitization. This study investigates the effect of diabetes on DSM calcium sensitization. Diabetes was induced by alloxan in New Zealand White rabbits, and age-matched rabbits given 5% sucrose in the drinking water served as control for diuresis. Two-dimensional gel electrophoresis showed that basal MLC phosphorylation level was significantly higher in diabetic animals than normal or diuretic controls, and Rho-kinase-specific inhibitor, Y-27632, decreased MLC phosphorylation level. Adding Y-27632 to bethanechol-precontracted DSM strips can induce muscle relaxation, but it occurred much more slowly in diabetic samples compared with controls. RT-PCR, Western blot analysis, and immunohistochemistry revealed the overexpression of Rho-kinase beta and CPI-17 at both mRNA and protein levels in response to diabetes. In conclusion, our results demonstrate that Rho-kinase contributes to DSM MLC phosphorylation and there is a higher basal MLC phosphorylation level in diabetic DSM. Our results also suggest that this high basal MLC phosphorylation may be due to the upregulation of Rho-kinase and CPI-17. Thus Rho-kinase- and CPI-17-mediated Ca(2+) sensitization might play a role in diabetes-induced alteration of the detrusor contractility and bladder dysfunction.

Modification of cardiac oxidative stress in alloxan-induced diabetic rabbits with repaglinide treatment

The aim of this study was to analyze the antioxidative effect of repaglinide in the heart of alloxan-induced diabetic rabbits. The activities of superoxide dismutase (Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), glutathione (GSH), ascorbic acid (AA), products of lipid peroxidation (LPO) and protein carbonyl groups (PCG) were estimated after 4 and 8 weeks of repaglinide treatment (1 mg daily). At significance level p < 0.05, in diabetic heart the activities of Cu,Zn-SOD and CAT were elevated as compared to control values (by 60.7% and 55.3% for Cu,Zn-SOD, and by 89.7% and 77.4% for CAT after 4 and 8 weeks, respectively). The level of AA was diminished by 52.5% and 41.5% while GSH-Px and GSSG-R activities were decreased after 4 weeks of experiment (by 11.5% and 14.4%, respectively). GSH level was diminished by 33.2% after 8 weeks. Simultaneously, in diabetic heart the levels of LPO and PCG were elevated as compared to control values (by 51.6% and 111.3% for LPO, and by 72.0% and 132.9% for PCG after 4 and 8 weeks, respectively). In diabetic animals, repaglinide normalized GSH-Px activity and GSH level. It modified the activities of Cu,Zn-SOD, CAT and AA as compared to diabetic non-treated animals. In diabetic-treated rabbits the level of LPO was diminished as compared to diabetic non-treated animals, while the level of PCG was not affected. In the present study, repaglinide did not affect blood glucose and plasma insulin concentrations in diabetic rabbits. Nevertheless, the drug showed some beneficial antioxidative properties in the heart tissue.

Activity of Angiotensin Peptides in Clitoral Cavernosum of Alloxan Induced Diabetic Rabbit

ObjectivesTo assess the role of peptides of the angiotensin (ANG) on the regulation of clitoral cavernosum tone and changes in ANG binding affinity in the rabbit with diabetes mellitus. Material and methodsThe isometric tension measurement and in vitro autoradiography were used in sham and diabetic clitoral cavernosum. ResultsIn tension study, contractility in response to ANG I, ANG II, ANG III and ANG IV was enhanced in diabetic clitoral cavernosum strips (EC50 was 67.6±27.2, 4.3±0.4, 189.3±37.3, 443.2±0.4nM for diabetic versus 155.2±76.1, 38.3±0.1, 528.0±75.2, 616.9±69.5nM for sham, respectively). Contractile responses to ANG II was significantly inhibited by type 1 ANG II receptor (AT1) antagonist but not by type 2 ANG II receptor (AT2) antagonist in both groups. Percentages in contractions by ANG II (1nM) in the presence of Dup 753 decreased significantly 36.2±4.6 to 6.3±2.4% in sham and 56.1±7.7 to 6.0±4.8% in diabetic group. The binding affinities were enhanced in diabetic clitoral cavernosum for ANG II (dissociation constant, 4.9±1.0 for sham versus 0.9±0.2nM for diabetic) and for ANG I, ANG III, and ANG IV (inhibitory constant, 28.6±1.5, 398.7±157.2, and 3966.5±1524.1nM for sham versus 20.6±5.7, 78.5±23.7, and 1098.7±195.5nM, for diabetic, respectively, all p<0.05). Sensitivities of AT1 and AT2 receptors to ANG II enhanced in diabetic than sham clitoral cavernosum tissue. ConclusionsThis results suggest that the contractile responses to all four ANG peptides are enhanced in the diabetic clitoral cavernosum. Enhancement of contractility in diabetic clitoral cavernosum may be related to the increased affinity to ANG II receptors for ANG peptides.

Oxidative stress in kidney and liver of alloxan-induced diabetic rabbits: effect of repaglinide

The aim of this study was to analyse the effect of the new oral antidiabetic drug repaglinide on antioxidant factors and lipid peroxidation in tissues of alloxan-induced diabetic rabbits after 4 and 8 weeks treatment. The activity of superoxide dismutase (diabetic vs. control values, mean+/-S.E.M., p<0.05) in diabetic kidney was diminished (1.5+/-0.2 vs. 2.8+/-0.3 and 1.8+/-0.1 vs. 2.9+/-0.3 U/mg protein) and significantly increased after 8 weeks of repaglinide treatment (2.4+/-0.2 U/mg protein). Catalase activity was significantly increased in diabetic liver (67.5+/-3.6 vs. 39.7+/-5.6 and 62.3+/-2.7 vs. 52.6+/-5.3 micromol H(2)O(2)/min/mg protein) and normalised by repaglinide (49.2+/-4.0 and 41.2+/-3.8 micromol H(2)O(2)/min/mg protein). In diabetic kidney the level of ascorbic acid was diminished after 4 weeks (1.5+/-0.1 vs. 3.0+/-0.1 micromol/g tissue) and increased after the drug treatment (2.0+/-0.2 micromol/g tissue). In diabetic kidney the level of lipid peroxidation products was elevated (33.3+/-2.4 vs. 23.7+/-2.4 and 29.5+/-3.1 vs. 18.2+/-0.8 nmol/g tissue) and diminished by repaglinide (10.3+/-1.4 and 13.3+/-3.0 nmol/g tissue). This study shows that oxidative stress in diabetic tissues is partly corrected by repaglinide. The drug does not affect glucose concentration and its antioxidative effect is not secondary to its action on hyperglycaemia. This study suggests an additional advantage of repaglinide which contributes to its effectiveness in therapy.

Modification of oxidative stress by pioglitazone in the heart of alloxan-induced diabetic rabbits

The study was undertaken to analyze the effect of pioglitazone on superoxide dismutase (Cu, Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), glutathione (GSH), ascorbic acid (AA), lipid peroxidation products (LPO) and protein carbonyl groups (PCG) in the heart of alloxan-induced diabetic rabbits after 4 and 8 weeks of pioglitazone treatment. In diabetic animals, Cu, Zn-SOD and CAT were elevated by 60 and 55%, and 90 and 77% as compared to controls at 4 and 8 weeks, respectively. GSH-Px, GSSG-R and GSH were diminished by 11, 14 and 33% as compared to controls at 4 or 8 weeks. AA was diminished by 52 and 41%. At P <0.05, pioglitazone normalized the activities of Cu, Zn-SOD, GSH-Px and GSSG-R. The activity of CAT was modified as compared to diabetic non-treated rabbits. After pioglitazone treatment, GSH and AA were increased as compared to diabetic non-treated animals. In diabetic rabbits, LPO was elevated by 52 and 111% and normalized by pioglitazone treatment. PCG was elevated by 72 and 133% and diminished as compared to diabetic non-treated animals at 8 weeks. The study shows that pioglitazone reduces oxidative stress in the heart of diabetic rabbits. In therapy, similar action can improve the cardiovascular system of diabetic patients.

Hypoglycemic and antidiabetic effect of ethanolic extract of leaves of Annona squamosa L. in experimental animals

The ethanolic extract of Annona squamosa L. (Annonaceae) leaves was administered orally at different doses to normal as well as streptozotocin (STZ)-induced diabetic rats and alloxan-induced diabetic rabbits. The dose of 350 mg/kg body weight (bw) reduced the fasting blood glucose (FBG) level by 6.0% within 1 h, whereas, the peak blood glucose at 1 h during glucose tolerance test (GTT) was reduced by 17.1% in normal rats. The same dose of ethanolic extract reduced FBG by 26.8% and improved glucose tolerance by 38.5 and 40.6% at 1 and 2 h, respectively, during GTT in alloxan-induced diabetic rabbits. In STZ-diabetic rats, a fall of 13.0% in FBG and an improvement in glucose tolerance by 37.2 and 60.6% at 1 and 2 h, respectively, was observed during GTT. The dose of 350 mg/kg bw of ethanolic extract in 10-day treatment of a group of STZ-diabetic rats produced 73.3% fall in FBG level and no sugar was observed in fasting urine. Treatment of severely-diabetic rabbits for 15 days with a dose of 350 mg/kg of extract reduce FBG by 52.7% and urine sugar by 75%. It brought about fall in the level of total cholesterol (TC) by 49.3% with increase of 30.3% in high-density lipoprotein (HDL) and decrease of 71.9 and 28.7% in low-density lipoprotein (LDL) and triglycerides (TG) levels, respectively.