Non-diabetic Rabbits Research Articles

Physiological Effects of Alloxan on Serum Glucose Levels and Liver Function Test in Male Rabbit

Diabetes is a metabolic disorder characterized by elevated blood glucose levels that can lead to various complications. Exploring the physiological alterations in rabbits can provide valuable insights for the development of therapeutic interventions. This research delves into the impact of diabetes on the physiological and biochemical parameters of male rabbits. Objectives: To compare the physiological parameters like body temperature, heart rate, respiration rate, and oxygen saturation) and body weight and biochemical parameters, including blood glucose levels, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, lactate dehydrogenase (LDH), and total protein levels in diabetic and non-diabetic rabbits. Methods: An experiment on 30 male rabbits divided into diabetic and control groups measured physiological parameters like body temperature, heart rate, respiration rate, and oxygen saturation. Body weight and blood glucose levels were tracked, and blood samples were taken for ALT, AST, creatinine, LDH, cholesterol, triglycerides and total protein levels. Statistical analysis was conducted to compare the physiological and biochemical parameters between the diabetic and control groups. Results: The results showed that induced diabetes in male rabbits affects their physiological and biochemical parameters significantly. Diabetic rabbits had lower body temperature, heart rate, respiration rate, and oxygen saturation compared to the control group. They also had higher body weight and blood glucose levels. Biochemical analysis showed increased ALT, AST, and creatinine levels, and decreased LDH and total protein levels in diabetic rabbits. Conclusions: These results demonstrate the extensive impact of diabetes on rabbit physiology and biochemistry, offering insights for future diabetes research.

Distinct MicroRNAs Identified in Rabbit Blood Arising from Induced Diabetes and a Surgically Simulated Diabetic Ischemia Complication.

Diabetic complications have been studied extensively in recent years. There are very few biomarkers in body fluids that can pinpoint a distinct diabetic complication due to insufficient known specific biomarkers for ischemia. Identifying microRNA in animal models for each complication could enable early diagnosis of a given complication if verified in humans. MicroRNA (miRNA) profiling has been done in rodent models for a number of diabetic complications, like diabetic glomerular injury, atherosclerosis, cognitive impairment, diabetic wound healing, angiopathy and other complications. Due to multiple differences between rodents and humans, the changes in rabbit skin, considered closer to humans than even pigs, may better simulate human diabetic complications of ischemia. To study the miRNA profile of rabbits in which diabetes was induced or ischemia was surgically generated, we studied whether diabetes or ischemia-induced specific miRNA could be detected. MicroRNA from the blood of diabetic rabbits and rabbits with local ischemia was collected in PAXgene Blood RNA tubes specifically designed for miRNA isolation and extracted using the PAX gene miRNA extraction kit. The isolated RNA was quality controlled using an RNA analyzer, and further, using RNA seq technology, it was analyzed for distinct miRNAs that were detected in diabetic and non-diabetic rabbits induced with ischemia. A miRNA that was found to be expressed in diabetic rabbits and ischemic rabbits but not in untreated rabbits was miRNA-183. Several miRNAs were differentially expressed across comparison groups, and several upregulated miRNAs were identified being unique to each comparison. In rabbits with a potential diabetic complication of a long-term ischemic model, there was one distinct microRNA, which was highly significantly upregulated in ischemia rabbit (miRNA-133-3p). One miRNA that was highly significantly upregulated in diabetic rabbit but not in ischemic rabbits was miRNA-3074-5p. Only statistically significant results have been considered and analyzed. These findings could lead to a precise and timely diagnosis of a potential single diabetic complication without invasive tissue biopsies and could be a novel tool in the management of diabetic patients developing complications due to the progression of diabetes.

Evaluation of Healing and Microbial Responses to Surgical Wounds in Alloxan-induced Diabetic Rabbits

The wounds of diabetic patients are associated with delayed healing and microbial invasion. This study evaluated the healing and microbial responses to surgical wounds in diabetic rabbits. Sixteen (16) New Zealand White rabbits were used in this study. They were divided into 4 groups of 4 rabbits each, namely; A, B, C and D. A is the control (non-diabetic and non-wounded), B (diabetic and non-wounded), C (wounded and non-diabetic) and D (wounded and diabetic). Three (3) cm2 skin wounds were created in a standard aseptic condition while diabetes was induced by intravenous administration of 200 mg/kg of alloxan monohydrate. Blood samples were collected from ear vein of each rabbit on days 0, 3, 7, 14, 21 and 28 post-surgery for analysis of blood glucose level. Wound samples were collected on days 3, 7, 14 and 21 to evaluate microbial contaminants. The wounds were examined for exudation and recorded as none (0), scant (1), moderate (2) and large (3) and diameter of wound epithelialization and contraction were determined. The blood glucose concentration of groups B and D from days 3 to 28 ranged between 288.00 ± 40.22 mg/dl to 358.65 ± 25.89 mg/dl), and were significantly higher (P < 0.05) than the corresponding values of groups A and C which ranged from 120.60 mg/dl ± 14.29 to 129.60 ± 8.18 mg/dl. The rate of wound contraction in the C group on day 7 (11.02 ± 2.17%) was significantly higher (P < 0.05) than the D group (2.23 ± 4.60%). Staphylococcus and Pseudomonas subspecies were identified in the wounds of rabbits in groups C and D. It was concluded that alloxan-induced diabetes caused delayed wound healing. At the same time Staphyloccocus and Pseudomonas species were the predominant microorganism detected in the acute wounds of diabetic and non-diabetic rabbits.

MODULATION OF SYMPATHETIC NERVE ACTIVITY BY SGLT2 INHIBITOR EMPAGLIFLOZIN IN DIABETIC RABBITS

Objective: Treatment with the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin in patients with type-2 diabetes is associated with 38% reduction in cardiovascular mortality. We explored the notion that the mechanisms underlying these benefits may involve an action on the sympathetic nervous system (SNS). Design and method: Diabetes was induced by alloxan in New-Zealand White rabbits. We determined the associated changes in blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) as well as baroreflex responses to changes in BP and norepinephrine spillover in conscious rabbits. The effects of one-week treatment with empagliflozin were compared to those of another blood glucose-lowering treatment insulin, the proximally-acting natriuretic acetazolamide, the ACE inhibitor perindopril, vehicle treatment and to an untreated diabetic group. Results: Diabetic rabbits were treated with daily insulin to maintain a stable elevation in blood glucose over 4 weeks (20.5 ± 0.4 mM vs 6.5 ± 0.4 mM in controls). BP was 9% greater in diabetic than non-diabetic rabbits (P = 0.02) but there were no differences in RSNA or HR. One-week treatment with empagliflozin (without insulin) lowered blood glucose by 43% but there was no difference in BP, HR or RSNA between these animals and untreated diabetic rabbits or those treated with acetazolamide. However, insulin treatment alone lowered blood glucose similarly to empagliflozin (32%) and increased HR (+10%) while perindopril lowered BP (-9%). In diabetic rabbits there was marked augmentation of the maximum RSNA response to baroreceptor unloading compared to non-diabetic (+69%, P < 0.01). Empagliflozin attenuated the baroreflex by 34% and there was a similar reduction after acetazolamide (-29%, both P < 0.05). Empagliflozin also attenuated the HR baroreflex (-8%) but insulin and perindopril had no effect on either baroreflex. Norepinephrine spillover to plasma was similar in diabetic and non-diabetic rabbits but was elevated after both empagliflozin and acetazolamide (+147% and + 134%, P < 0.05). Conclusions: Empagliflozin normalised the maximal RSNA response to lowering BP, which was exaggerated in diabetic rabbits, without altering BP or resting RSNA. A similar action of the natriuretic acetazolamide suggests that the mechanism underlying the cardiovascular benefits of empagliflozin may involve increased sodium and water excretion.

Empagliflozin modulates renal sympathetic and heart rate baroreflexes in a rabbit model of diabetes.

We determined whether empagliflozin altered renal sympathetic nerve activity (RSNA) and baroreflexes in a diabetes model in conscious rabbits. Diabetes was induced by alloxan, and RSNA, mean arterial pressure (MAP) and heart rate were measured before and after 1week of treatment with empagliflozin, insulin, the diuretic acetazolamide or the ACE inhibitor perindopril, or no treatment, in conscious rabbits. Four weeks after alloxan administration, blood glucose was threefold and MAP 9% higher than non-diabetic controls (p < 0.05). One week of treatment with empagliflozin produced a stable fall in blood glucose (-43%) and increased water intake (+49%) but did not change RSNA, MAP or heart rate compared with untreated diabetic rabbits. The maximum RSNA to hypotension was augmented by 75% (p < 0.01) in diabetic rabbits but the heart rate baroreflex was unaltered. Empagliflozin and acetazolamide reduced the augmentation of the RSNA baroreflex (p < 0.05) to be similar to the non-diabetic group. Noradrenaline (norepinephrine) spillover was similar in untreated diabetic and non-diabetic rabbits but twofold greater in empagliflozin- and acetazolamide-treated rabbits (p < 0.05). As empagliflozin can restore diabetes-induced augmented sympathetic reflexes, this may be beneficial in diabetic patients. A similar action of the diuretic acetazolamide suggests that the mechanism may involve increased sodium and water excretion. Graphical abstract.

Treatment with SGLT2 Inhibitor Empagliflozin Modulates Renal Sympathetic Nerve Activity in Diabetic Rabbits

In patients with type 2 diabetes, antihyperglycemic treatment with the sodium‐glucose cotransporter 2 (SGLT2) inhibitor empagliflozin is associated with a reduction in cardiovascular mortality of 38% (EMPA‐REG OUTCOME trial). In individuals with poorly controlled type 2 diabetes, sympathetic nervous system (SNS) activation is associated with poor cardiovascular outcomes. We explored the notion that the mechanisms underlying the cardiovascular benefits of empagliflozin treatment may involve an action on the SNS.Diabetes was induced by a single dose of alloxan in New Zealand White rabbits. We determined the changes in blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) as well as baroreflex responses to changes in BP and norepinephrine spillover in conscious rabbits. The effects of one‐week treatment with empagliflozin were compared to those of another blood glucose‐lowering treatment insulin, the proximally‐acting natriuretic acetazolamide, the ACE inhibitor perindopril, vehicle treatment and to an untreated diabetic group.Diabetic rabbits (n=39) were treated with daily insulin to maintain a stable elevation in blood glucose (20.5±0.4mM vs 6.5±0.4mM in controls) over 4 weeks. Diabetes was associated with 9% greater BP than in non‐diabetic rabbits (P=0.02) but no difference in RSNA or HR. One‐week treatment with empagliflozin lowered blood glucose by 43% (without insulin), and there was a 49% increase in water intake. There was no difference in BP, HR or RSNA between empagliflozin‐treated and untreated diabetic rabbits or those treated with acetazolamide. However, insulin lowered blood glucose similarly to empagliflozin (32%) and increased HR (+10%) while perindopril lowered BP (−9%). There was marked augmentation (+69%) of the maximum RSNA response to baroreceptor unloading in diabetic rabbits compared to non‐diabetic (P&lt;0.01). Empagliflozin attenuated the baroreflex by 34% and acetazolamide had a similar blunting effect (−29%, both P&lt;0.05). Empagliflozin also attenuated the HR baroreflex (−8%) but insulin and perindopril had no effect on either baroreflex. Diabetes did not alter BP or HR variability but empagliflozin and acetazolamide treatment increased mid frequency HR power. Norepinephrine spillover to plasma was similar in diabetic and non‐diabetic rabbits but was elevated after both empagliflozin (+147%) and acetazolamide (+134%, P&lt;0.05).In conclusion, empagliflozin effectively normalized the maximal RSNA response to acute BP lowering without altering resting hemodynamic or sympathetic activity in conscious diabetic rabbits. The similarity of these effects with those of acetazolamide suggests that the mechanism underlying the cardiovascular benefits of empagliflozin is linked to its natriuretic action.Support or Funding InformationThis work was supported by Boehringer Ingelheim.

Numerical simulation of haemodynamics of the descending aorta in the non-diabetic and diabetic rabbits

Diabetes mellitus (DM) is a predisposing risk factor leading to macrovascular diseases. Changes in haemodynamics of the diabetic aortas remain largely unclear and relevant computational analyses are lacking in the literature. Ten adult rabbits (1.6–2.2 kg) were collected and the type I diabetic rabbit model was induced by injection of alloxan. A total of five control and five diabetic rabbit aortas were considered for subsequent numerical simulation. The CT scanning was performed to reconstruct three-dimensional model of the individual rabbit descending aorta. The flow velocity waveforms were measured by ultrasound machine and were set to be the inlet boundary conditions. The reconstructed aortas were then imported into ANSYS to perform mesh generation and computational analysis. Results showed that the distributions of haemodynamic indicators time-averaged wall shear stress (TAWSS), oscillating shear index (OSI) and transverse wall shear stress (transWSS) in the non-diabetic rabbit aortas were similar to those in the diabetic rabbit aortas. However, the mean values of TAWSS and transWSS in the non-diabetic rabbit aortas were significantly higher than those values in the diabetic rabbit aortas (TAWSS: p = 0.04; transWSS: p = 0.02). The back of right renal artery tended to have high OSI in both the non-diabetic and the diabetic rabbit aortas. Notably, the regions with high OSI tended to have intense disturbed flow and low TAWSS in the most diabetic rabbit aortas. The results suggest that diabetes leads to changes in haemodynamic parameters in the rabbit aortas. In particular, the lower TAWSS and the higher OSI within the diabetic aortas may further contribute to aortic wall remodeling.

Leukocyte- and platelet-rich fibrin as graft material improves microRNA-21 expression and decreases oxidative stress in the calvarial defects of diabetic rabbits

ObjectiveLeukocyte- and platelet-rich fibrin (L-PRF) represents a natural, low-cost product which may promote tissue healing by mechanisms not fully elucidated. Diabetes mellitus (DM) disrupts bone healing by inducing inflammation and oxidative stress (OS), mechanisms regulated by microRNAs (miRs). The aim of the present study was to investigate the microRNA-21 (miR-21) involvement in diabetic bone regeneration using L-PRF alone or in combination with a standard grafting material. DesignAfter the induction of diabetes (alloxan 100 mg/kg), four cranial osteotomies were made in diabetic (n = 12) and non-diabetic (n = 12) rabbits: one was left empty and the remaining three were grafted with L-PRF, bovine hydroxyapatite (Bio-Oss®) and L-PRF + Bio-Oss®. Two and eight weeks postoperatively, the samples were harvested for miR-21 expression (Real-time RT-PCR) and enzyme-linked immunosorbent assay analyses. ResultsDiabetic rabbits showed decreased miR-21 and matrix metalloproteinase-9 (MMP-9) protein expression while increased malondialdehyde (MDA) levels two weeks postoperatively; however, there were no significant differences in miR-21 and MMP-9 levels between diabetic and non-diabetic rabbits in samples taken eight weeks postoperatively. Application of L-PRF and L-PRF + Bio-Oss® improved miR-21 and MMP-9 and decreased MDA levels while Bio-Oss® alone enhanced superoxide dismutase (SOD) activity levels in diabetic rabbits. ConclusionL-PRF alone or in combination with bovine hydroxyapatite as bone graft could be beneficial in DM since it seems to improve inflammation-modulatory miR-21 expression and decreases oxidative stress.

Antioxidant Enzymes and Lipid Peroxidation in Alloxan-Induced Diabetic Rabbits

The study was carried out to evaluate the effect of alloxan–induced diabetes on some oxidative stress markers in rabbits. Ten rabbits weighing between 1.0-1.5kg were used and divided into two groups of five rabbits each. Diabetes was induced in one of the groups, by intraperitonial administration of alloxan at a dosage of 150mg/kg body weight and the control rabbits were administered normal saline (0.9% NaCl). The animals were monitored for 14days after confirmed diabetes in the test group. The fasting plasma glucose, plasma insulin, plasma lipids, the antioxidant enzymes: Superoxide dismutase (SOD), catalase, and lipid peroxidation were assayed for, in the plasma and the brain of the diabetic and non-diabetic rabbits. The results showed a significant decrease in mean body weight of the alloxan-induced diabetic and control rabbits pre and 14days post alloxan-induction. There was a significant (p < 0.01) increase in fasting plasma glucose, a significant (p < 0.01) decrease in the activity of SOD and a significant (p < 0.01) increase in the activity of catalase in the plasma and brain; there was also a significant (p < 0.01) increase in the level of lipid peroxidation, plasma cholesterol and triglycerides in the diabetic rabbits. Culminating a depletion of SOD activity, the altered activity of plasma (or brain) catalase and increased lipid peroxidation is due to the oxidative stress induced by the diabetic condition, hence the present study indicate that alloxan – induced diabetic potentiated oxidative stress in a short term duration. This shows the importance of antioxidant mimetics to be administered at early stage of diabetics in other to increase the antioxidant capacity thus preventing oxidative stress which may lead to complication in diabetes.

Effects of diabetes mellitus on biomechanical properties of the rabbit cornea

To investigate the effects of diabetes on the biomechanical behavior of cornea in alloxan-induced diabetic rabbits. Diabetes mellitus (DM) was induced in 20 rabbits using alloxan, while another 20 age- and weight-matched non-diabetic rabbits served as controls. Eyes were enucleated after 8 weeks of inducing diabetes and the whole cornea was removed with a 3 mm wide scleral ring and tested under inflation conditions with an internal pressure range of 2.0–30.0 mmHg to determine their stress-strain behavior using an inverse analysis process. The blood glucose level (BG), advanced glycosylation end products (AGEs), central corneal thickness (CCT) and intraocular pressure (IOP) increased significantly in the DM group. There were statistically significant correlations between BG and AGEs (r = 0.768, p = 0.00), and between AGEs and CCT variation upon induction of DM (r = 0.594, p = 0.00). The tangent modulus (Et) of the cornea at four stress levels (1–4 kPa, equivalent to approximately IOP of 7.5, 15, 22.5 and 30 mmHg, respectively) was significantly higher in diabetic rabbits than in the control group (p < 0.05). Further, Et at stress of 2 kPa (which corresponded to the average IOP for the control group) was significantly correlated with BG (r = 0.378, p < 0.05), AGEs (r = 0.496, p < 0.05) and CCT variation upon induction of DM (r = 0.439, p < 0.05). IOP, as measured by contact tonometry, was also significantly correlated with both CCT (r = 0.315, p < 0.05) and Et at 2 kPa (r = 0.329, p < 0.05), and even after correcting for the effects of CCT and Et, IOP still significantly increased with both AGEs (r = 0.772, p = 0.00) and BG (r = 0.762, p = 0.00). The cornea of diabetic rabbits showed a significant increase in mechanical stiffness as evidenced by increases in corneal thickness and tangent modulus. The Et increase may be explained by a non-enzymatic cross-linking of collagen fibrils mediated by AGEs due to the high blood glucose levels in diabetes. The study also found significant IOP increases with higher blood glucose level even after controlling the effects of both corneal thickness and tangent modulus.

An acute experimental study to evaluate the effect of gatifloxacin on blood sugar levels in diabetic and non-diabetic rabbits

Background: Diabetes mellitus is a condition characterized by chronic hyperglycemia and disturbance of carbohydrate, fat and protein metabolism associated with absolute or relative deficiencies in insulin secretion and/or insulin action. The objective of this study was to evaluate the effects of gatifloxacin on blood sugar levels in non-diabetic rabbits and alloxan induced diabetic rabbits. Methods: Animals were fasted for 20 hours. Blood was collected for baseline investigations. After giving single oral dose of 2% gum acacia blood samples were drawn at 1, 2 and 4 hours for estimation of glucose and serum insulin. After 2 days a repeat blood sample for baseline was collected after 20 hours fasting and single oral dose of gatifloxacin 25 mg/kg was given. Samples of blood were taken at 1, 2 and 4 hours. After a wash out period of 7 days injection alloxan 140 mg/kg was given slowly intravenously to induce diabetes in the animals. On day 3 after alloxan induction, blood samples were taken from the animals (fasting 20 hours), for baseline investigations. Same procedure of blood collection and timing was followed as done before diabetes induction. The animals were given a single dose of gatifloxacin 25 mg/kg with blood samples drawn at 1, 2 and 4 hours for FBS and serum insulin. Results: In non-diabetic rabbits, the effect of control and gatifloxacin on FBS levels at 1, 2 and 4 hours after administration was 100.3, 101.35, 102.89 mg/dl and 73.83, 73.04, 82.11 mg/dl respectively, on serum insulin levels at 2 hours interval was 3.62 and 4.16 μ IU/ml respectively. 48 hours after alloxan induction FBS and insulin levels were 219.13 and 1.19 μ IU/ml. After alloxan induction, FBS levels at 1, 2, 4 hours for control and gatifloxacin are 221.01, 224.13, 228 and 218.60, 218.53, 220.01 respectively. At 2 hours interval serum insulin levels were 1.15 and 1.21 μ IU/ml for control and gatifloxacin. Conclusions: This study is in line with previous reports that gatifloxacin causes increased release of insulin leading to hypogycemia. The fall in blood sugar levels following a single oral dose of gatifloxacin is not limited to diabetic states alone and is more marked in non-diabetic rabbits.

Reduced muscarinic parotid secretion is underlain by impaired NO signaling in diabetic rabbits.

The influence of experimental diabetes (alloxan, 100mgkg(-1) ) was studied on rabbit parotid gland function. Carbachol-induced parotid secretion in vivo, and in vitro quantification of inducible nitric oxide synthase (iNOS) mRNA expression, by real-time RT-PCR, and activity of superoxide dismutase (SOD) and total antioxidant capacity (TAC) in commercial colorimetric assays were measured in parotid glands of non-diabetic and diabetic rabbits. Carbachol-induced dose-dependent increase in parotid secretion significantly reduced in diabetic rabbits. Functional studies in the presence of muscarinic receptor and nitric oxide synthase (NOS) antagonists revealed that in M3 receptor-mediated carbachol secretion, nitric oxide, deriving mainly from neuronal NOS (nNOS) in control, and iNOS in diabetic rabbits, was involved. Also, upregulation of iNOS mRNA expression and enhanced SOD activity and TAC were detected in diabetic glands. Our data suggest that decreased M3 receptor-mediated parotid secretion in diabetic rabbits appears to be due to alterations in NO signaling, mainly due to iNOS induction, accompanied by elevated antioxidant response.

Effects of polysaccharide from pumpkin on biochemical indicator and pancreatic tissue of the diabetic rabbits

A water-soluble polysaccharide (PCE-CC) was obtained from pumpkin which belongs to the family Cucubitaceae by the water and ethanol extract, organic solvent fractional extraction and deproteinization. The present study was designed to investigate PCE-CC possible mechanism underlying the improvement of damaged pancreatic islets. Alloxan-induced diabetic rabbits were injected with PCE-CC for 21 days to assess effects on islet tissue morphology. After 21 days, the weights of the alloxan-induced diabetic and non-diabetic rabbits fed with diet contained PCE-CC were significantly increased as compared to the negative group. The data of blood glucose (BG), total cholesterol (TC), total triglyceride (TG) and glycosylated hemoglobin (HbA1c) indicated that PCE-CC had beneficial effects on the improvement in the control of blood glucose, serum lipid and glycosylated hemoglobin levels. Observing the pancreatic tissue of the diabetic rabbits revealed that PCE-CC could promote the regeneration of damaged pancreatic islets by stimulating β-cell proliferation, which was accompanied by a decrease in plasma glucose levels. PCE-CC was further separated and purified to obtain PCE-CCH by ion exchange and gel chromatography. PCE-CCH was a heteropolysaccharide and consisted of glucose, galactose, arabinose, rhamnose and little amount of hexuronic acid, with a molecular weight of 1.15×105Da.

Study of hypoglycemic activity of Tinospora cordifolia in alloxan induced diabetic rabbits

Background: This study was designed to investigate the hypoglycemic effect of Tinospora Cordifolia in alloxan-induced diabetic rabbits. Methods: Rabbits were divided into four experimental groups: Non-diabetic rabbits treated with normal saline, Non-diabetic rabbits treated with TCREt, Diabetic rabbits treated with Metformin, Diabetic rabbits treated with TCREt. Treatment with drugs was started on the 8th day of alloxan treatment (i.e. day 1) and was continued for 30 days. Statistical evaluation was done using student’s ‘t’ test &amp; one way ANOVA followed by Tuckey`s post hoc test. ‘p’ value less than 0.05 was considered statistically significant. Results: TCREt showed hypoglycemic action in alloxan induced diabetes rabbits. It did not produce hypoglycemia in non diabetic rabbits. Conclusion: Hypoglycemic action of TCREt is comparable to that of standard oral hypoglycemic drug metformin.

Beneficial Effects of Pentanema vestitum Linn. Whole Plant on the Glucose and Other Biochemical Parameters of Alloxan Induced Diabetic Rabbits

The residents of Lower Dir and Malakand agency, Khyber Pakhtunkhwa, Pakistan, use the dry powder of whole plant of Pentanema vestitum for the treatment of asthma and diabetes. No documented reports are available about the therapeutic action of Pentanema vestitum. The present study was aimed to explore the antihyperglycemic effect of 70% methanol extract of Pentanema vestitum whole plant in glucose-induced nondiabetic hyperglycemic and alloxan-induced diabetic rabbits. During this study, the effects of plant extract on the serum lipid profile, GPT, ALP, bilirubin and creatinine of diabetic rabbits were also studied. The extract of Pentanema vestitum whole plant exhibited significant (P < 0.05) antihyperglycemic activity in glucose-induced hyperglycemic rabbits. Treatment of alloxan-induced diabetic rabbits with extract significantly (P < 0.05) reduced the elevated levels of serum glucose, GPT, ALP, bilirubin and creatinine. During the study of lipid profile, the extract proved to be antihyperlipidemic and HDL boosting in diabetic rabbit models. From the finding of the present research, it was concluded that the 70% methanol extract of Pentanema vestitum whole plant has beneficial effects on serum levels of glucose, lipid profile, GPT, ALP, bilirubin, and creatinine of diabetic rabbits.

Effects of aqueous extract of Triplochiton scleroxylon on some haematological parameters and blood glucose concentrations in non-diabetic rabbits

Investigations on possible effects of aqueous extract of Triplochiton scleroxylon on some haematological parameters and glucose concentrations in non-diabetic rabbits were carried out. At least 100 ml of extract was administered daily for 15 days to test rabbits (New Zealand strain) through clean water troughs. Blood was drawn with the aid of sterile syringes from the large vein at the back of the ears of rabbits. Swelab auto-counter 920 E+ (UK) was used in haematological analysis while blood glucose concentrations were determined by glucose oxidase procedures involving spectrophotometry. Aqueous extract of T. scleroxylon did not have significant effects (P > 0.05) on the haematological parameters (mean hemoglobin concentration, packed cell volume, white blood cell, lymphocyte and neutrophil counts) examined in non-diabetic rabbits when compared to normal control. However, it caused significant decrease (P < 0.05) in plasma glucose concentrations obtained on the 13th through 15th day of administration to the test rabbits. Aqueous extract of T. scleroxylon had hypoglycemic properties but does not contain lethal concentrations of chemical substances capable of adverse interference on the haematological parameters to cause any form of blood disorder. Key words : Triplochiton scleroxylon, haematological parameters, non-diabetic rabbits.

Creating a long-term diabetic rabbit model.

This study was to create a long-term rabbit model of diabetes mellitus for medical studies of up to one year or longer and to evaluate the effects of chronic hyperglycemia on damage of major organs. A single dose of alloxan monohydrate (100 mg/kg) was given intravenously to 20 young New Zealand White rabbits. Another 12 age-matched normal rabbits were used as controls. Hyperglycemia developed within 48 hours after treatment with alloxan. Insulin was given daily after diabetes developed. All animals gained some body weight, but the gain was much less than the age-matched nondiabetic rabbits. Hyperlipidemia, higher blood urea nitrogen and creatinine were found in the diabetic animals. Histologically, the pancreas showed marked beta cell damage. The kidneys showed significantly thickened afferent glomerular arterioles with narrowed lumens along with glomerular atrophy. Lipid accumulation in the cytoplasm of hepatocytes appeared as vacuoles. Full-thickness skin wound healing was delayed. In summary, with careful management, alloxan-induced diabetic rabbits can be maintained for one year or longer in reasonably good health for diabetic studies.

Gene Expression of Pro-Inflammatory Cytokines and Neuropeptides in Diabetic Wound Healing

The interaction between neuropeptides and cytokines and its role in cutaneous wound healing is becoming evident. The goal of the present study is to investigate the impact of diabetes on peripheral cytokine and neuropeptide expression and its role in diabetic wound healing. To achieve this goal, the effect of diabetes on wound healing, along with the role of inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-8 (IL-8) secreted in the wound microenvironment, and neuropeptides such as substance P (SP) and neuropeptide Y (NPY), secreted from peripheral nerves is monitored in non-diabetic and diabetic rabbits. Rabbits in the diabetic group received alloxan monohydrate (100mg/kg i.v.). Ten days after diabetic induction, four full thickness circular wounds were created in both ears using a 6mm punch biopsy. Wound healing was monitored over 10 d and gene expression of cytokines and neuropeptides was assessed in the wounds. Compared with the non-diabetic rabbits, wounds of diabetic rabbits heal significantly slower. Diabetic rabbits show significantly increased baseline gene expression of IL-6 and IL-8, their receptors, CXCR1, CXCR2, GP-130, and a decrease of prepro tachykinin-A (PP-TA), the precursor of SP, whereas the expression of prepro-NPY (PP-NPY), the precursor of NPY is not different. Similarly, baseline protein expression of CXCR1 is higher in diabetic rabbit skin. Post-injury, the increase over baseline gene expression of IL-6, IL-8, CXCR1, CXCR2, and GP-130 is significantly less in diabetic wounds compared with non-diabetic wounds. Although there is no difference in PP-TA gene expression between non-diabetic and diabetic rabbits post-injury, the gene expression of PP-NPY is reduced in diabetic rabbits. In conclusion, diabetes causes dysregulation in the neuropeptide expression in the skin along with a suppressed focused inflammatory response to injury. This suggests that the chronic inflammation in the skin of diabetic rabbits inhibits the acute inflammation much needed for wound healing.

Topical application of naltrexone facilitates reepithelialization of the cornea in diabetic rabbits

Delayed corneal reepithelialization is a complication of diabetes, and may lead to ulcers and erosions, which cause ocular morbidity and visual loss. This study examined the efficacy of naltrexone (NTX), a long-acting, potent opioid antagonist, applied topically, to facilitate the repair of standardized corneal abrasions in diabetic (alloxan-induced) New Zealand White rabbits (glucose levels > 450 mg/dL). NTX at a concentration of 10 −4 M, or sterile vehicle (SV), was administered topically 4 times per day for 7 days to the abraded eye of uncontrolled Type 1 diabetic (DB), insulin-controlled Type 1 diabetic (DB-IN), or non-diabetic (Normal) rabbits. Wound healing was monitored, and non-invasive (tonopen, pachymeter, hand-held slit lamp, and retinal camera) and invasive (histopathology) measurements evaluated. Corneal reepithelialization in the uncontrolled DB rabbits was significantly enhanced (up to a 47% reduction in wound area) following treatment with NTX relative to both Normal SV and DB SV rabbits at 24, 48, and 56 h following surgery. At 72 h, DB NTX rabbits had residual defects that were 64–82% smaller than Normal and DB SV animals. NTX treated DB-IN rabbits had residual defects that were 9–37% smaller than DB-IN rabbits receiving SV, and 6–40% smaller than Normal rabbits. No signs of toxicity from topical applications were noted. These data confirm and extend those documented in rats that demonstrated a lack of toxicity of NTX at a wide range of dosages, as well as efficacy for enhanced corneal epithelialization. These studies set the stage for clinical trials using NTX as a therapy for diabetic keratopathy.

Influence of an Aqueous Extract of Azadirachta indica Leaf on the Pharmacodynamics and Pharmacokinetics of Gliclazide in Rats and Rabbits

In diabetes, optimal blood sugar control is needed to maintain health. Both allopathic and herbal drug therapy medicinal plants are being used in therapy for diabetes, but interactions between these two types of medicine are unknown. To determine whether an herbal drug (the aqueous extract of Azadirachta indica leaves) altered the effects of allopathic treatment (gliclazide) of diabetes, this study monitored blood sugar in non-diabetic and diabetic rats and non-diabetic rabbits treated with gliclazide, A. indica extract, and a combination of these two drugs. Hypoglycemia in normal and diabetic rats reached a peak at 1 hour and 8 hours and in rabbits at 3 hours after administration of gliclazide. Administration of A. indica extract reduced blood sugar when given alone and prolonged the effect of gliclazide more than 8 hours in non-diabetic rats, beyond 12 hours in diabetic rats, and more than 8 hours in non-diabetic rabbits without hypoglycemic convulsions. The presence of A. indica extract did not alter the pharmacokinetics of gliclazide in rabbits. This study indicated that the combination of gliclazide and A. indica can be used safely to get prolonged and sustained antidiabetic effects.