Diabetic Guinea Pigs Research Articles

Efficiency of daily kombucha consumption in reducing glycemic levels and hypercholesterolemia

Diabetes is one of the most common comorbidities in the world. The scientific community is constantly looking for therapeutic alternatives, pharmacological or not, to treat this disease. In this concern, an integrative review of studies published on this topic in the last ten years was carried out. Experimental studies have shown glycemic and lipid rates reduction in diabetic guinea pigs under daily kombucha consumption. Such studies showed blood sugar levels reduction of up to 56% of these specimens, as well as a significant reduction of free radicals, hepatoprotection and reduction of transaminases in these animals.

Effect of Perfluorooctanoic Acid on Kidney Function in Diabetic and Non-‎‎Diabetic Male Guinea Pigs

Perfluorooctanoic acid (PFOA) is a synthetic fluor-surfactant chemical used widely in ‎products that resist oil, heat, grease, stains, and water. It is also used in producing other ‎fluoropolymers. The main sources of exposure to PFOA are water, soil, and animal-‎origin food (meat, fish, and dairy products). The aim of this study to evaluate the renal ‎function following oral gavage of sub-lethal dose of PFOA in diabetic and non-diabetic ‎guinea pigs. The experiment run for 4 weeks, total of 40 male guinea pigs, ‎‎(Cavia porcellus), were randomly selected and grouped into four equal groups. The first ‎group (G1) served as the negative control; 2nd group (G2) alloxan induced diabetic, 3rd ‎group (G3) non-diabetic was exposed to PFOA at 100 mg/kg BW orally/daily and 4th ‎Group (G4) was diabetic guinea pig exposed to PFOA at 100 mg/kg BW orally/daily. ‎Serum creatinine and histopathological alterations in the kidney tissue were evaluated. ‎Serum creatinine concentrations were significantly increased (P<0.05) in G3 and G4 ‎exposed to PFOA. High serum creatinine levels were suggesting impairment in kidney ‎function. Impaired kidney function was confirmed through histopathological changes ‎such as glomerular atrophy, severe necrosis, and degeneration of renal tubular epithelium ‎in guinea pigs that received PFOA in G3 and G4. In conclusion, the results confirmed ‎that PFOA was associated with renal damage and elevated creatinine concentrations in ‎diabetic and non-diabetic animals since PFOA itself can contribute to diabetes‎‎‎.

Molecular modelling and biological evaluation of phyto-molecules as potential activators of gluconolactone oxidase (GULO)

Diabetes, the cause of colossal economic and disease burden, is a key area of research in drug discovery programs. Elevated blood glucose levels in diabetes lead to several adverse consequences due to the formation of advanced glycation end products and free radicals. Vitamin C, a potent antioxidant, protects the body’s cells and tissues from oxidative damage and dysfunctions. Glucose is the precursor of Vitamin C synthesis in plants and some mammals. L-gulono lactone oxidase (GULO) is the rate-limiting enzyme in producing Vitamin C. However, it is not synthesized in bats, primates, humans, and guinea pigs because of the pseudogene. Several phytomolecules having antioxidant properties are hypothesized to be promising and selective activators of GULO. Therefore, the present study focused on screening agonists of GULO from phytomolecules as an effective augmentor for Vitamin C synthesis, thereby suppressing the sequela of diabetic events. The 3D structure of GULO was generated by the ab-initio method. Subsequently, molecular docking explored the possible binding patterns of GULO protein with different plant phenolic compounds, followed by supplementation of the potent phytomolecules to diabetic guinea pigs. It is noteworthy that Resveratrol and Hydroxytyrosol showed better binding affinity. The molecular simulation also confirmed that Resveratrol is an activator of the GULO enzyme. Interestingly, it was also established that Vitamin C levels were improved in diabetic guinea pigs supplemented with the phytomolecules and comparatively Resveratrol modulates the concentration of glucose and Vitamin C levels substantially, thereby alleviating hyperglycemia. However, further studies are warranted to study the mechanisms. Communicated by Ramaswamy H. Sarma

DIFFERENCES IN OSTEOBLAST COUNT AND ITS EFFECT ON ORTHODONTIC MOVEMENT OF DIABETIC MODELS’ TEETH AFTER ORAL ADMINISTRATION OF OLIVE OIL

Background: In patients with uncontrolled diabetes, an increase in Advanced glycation end products (AGEs) inhibits osteoblast differentiation so that the number of osteoblasts decreases and interferes with bone formation in orthodontic movement. Giving natural ingredients such as olive oil is proven to increase the number of osteoblasts. Purpose: To determine differences in the number of osteoblasts and their effect on the orthodontic movement of diabetic teeth after oral administration of olive oil. Method: 25 male guinea pigs divided into four groups: diabetic guinea pigs treated with olive oil at a dose of 0.7; 1.05; 1.4 ml/day, distilled water, and healthy guinea pigs were given aquadest. Alveolar bone tissue samples were taken on the 15th day after orthodontic application, and then the number of osteoblasts was calculated histologically. Result: In the diabetic model group treated with olive oil doses of 0.7; 1.05; 1.4 ml/day, distilled water, and healthy guinea pigs given aquades were 2.900 ± 0.678; 4.320 ± 0.497; 5.920 ± 0. 460; 0.200 ± 0.200; 1.320 ± 0.415. The study showed that the olive oil treatment group had more osteoblasts than the untreated group. Analysis one way ANOVA showed a very significant difference between the treatment group and the untreated group (p≤0.01), while the LSD test showed a significant difference between groups. The highest number of osteoblasts was found at a dose of 1.4 ml/day. Conclusion: There was an increase in osteoblasts in the orthodontic movement of diabetic teeth after oral administration of olive oil.

Expression of Osteopontin and Integrin αvβ3 Receptor in Retina of Diabetic Guinea Pigs with High Myopia

Introduction: The study aimed to investigate the effect of high myopia on the expression of retinal osteopontin (OPN) and integrin αvβ3 receptor in guinea pigs and determine the relationship between high myopia and diabetic retinopathy (DR). Methods: Ninety-three-week-old male guinea pigs were randomly divided into four groups that included normal control group (NOR, n = 18), high myopia group (HM, n = 24), diabetes group (DR, n = 24), and diabetes with high myopia group (DR+HM, n = 24). HM was induced by form deprivation (FDHM) in the right eye. The DR group was injected with 5% streptozotocin 280 mg/kg intraperitoneally in the lower left abdomen of guinea pigs. The DRHM group was subjected to the same treatment as the HM and DR groups. Eighteen guinea pigs in each group were randomly selected to complete the experimental measurement. After enucleation of eyeballs, HE and immunohistochemical staining were performed to observe the retina morphology and count the positive rate of OPN and integrin αvβ3 receptor. Results: Diabetic retinal changes were found in group DR and HM+DR. The degree of retinal change in group HM+DR was less than that in group DR. In the DR group, the morphology of retinal tissue was loose, the number of cells decreased, retinal microaneurysms were increased, and a small amount of small artery embolism and venous thrombosis were observed. Although the retinal structure in the HM+DR group also became thinner, looser, and disordered, only a small number of microaneurysms were observed compared with the diabetic group. Immunohistochemical staining showed that the expression of OPN and integrin αvβ3 receptors in the diabetic groups (DR, HM+DR) was significantly higher than in the HM and NOR groups. The positive expression rates of OPN and integrin αvβ3 receptors in group HM+DR were significantly lower than those in group DR (p < 0.05). Conclusion: The expression of OPN and integrin αvβ3 receptor in the retina of diabetic guinea pigs with high myopia was lower than that of diabetic models, which may be due to the influence of high myopia on neovascularization in DR.

The Effect of Using Chitosan and Nano-chitosan Synthesized from Blue Carb in the Treatment of Hyperglycemia and Glomerulus of Diabetic Guinea Pigs

Chitin, the most presence of biopolymer after cellulose, it consisting the major compound of crustacean shell. Chitosan is a biopolymer derived by deacetylation of chitin. Diabetes Mellitus (DM) is a collection of metabolic diseases characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both leading to metabolic abnormalities in carbohydrates, lipids, and proteins. Increasing the ROS level, damage the cell membrane lipid and proteins that change in cell metabolism thereby defect in function of tissue and organ. The aim of current study was to evaluate the effect of chitosan and nano-chitosan on guinea pigs with hyperglycemia. Diabetes induced by injection of dexamethasone for 5 weeks. Fasting plasma sugar significantly decrease in treatment groups (168.2±24.38 and 156.4±53.71). Also blood urea and creatinine levels significantly reduced in treatments groups.

The Effects of The Leaf Extracts of Vernonia Amygdalina, Ocimum Gratissimum and Phyllanthus Amarus on Blood Glucose Level of Alloxan-Induced Diabetic Guinea Pigs

The Effects of The Leaf Extracts of Vernonia Amygdalina, Ocimum Gratissimum and Phyllanthus Amarus on Blood Glucose Level of Alloxan-Induced Diabetic Guinea Pigs

Comparative Study of Hypoglycemic Effects of Aqueous Extracts of Leaves and Fruits of Garden Egg (Solanum melongena) In Alloxan Induced Diabetic Guinea Pigs

The aim of this research work was to carry out a comparative study on the aqueous extracts of the leaves and fruits of Garden egg (Solanum melongena) using alloxan induced diabetic guinea pigs. Blood glucose level analysis was used as diabetic indices. Z-test was used in comparing the mean fasting blood glucose level of alloxan induced diabetic guinea pigs after administration of aqueous leaf extracts and that of the aqueous extracts of the fruits of Garden egg (Solanum melongena) against the negative control (0.9%N/S) and positive control group (Glibenclamide solution).The results showed that there was a significant difference between the group that had oral administration of aqueous leaf extracts and the negative control group (p 0.05).

Mitochondrial respiration and ROS emission during β-oxidation in the heart: An experimental-computational study.

Lipids are main fuels for cellular energy and mitochondria their major oxidation site. Yet unknown is to what extent the fuel role of lipids is influenced by their uncoupling effects, and how this affects mitochondrial energetics, redox balance and the emission of reactive oxygen species (ROS). Employing a combined experimental-computational approach, we comparatively analyze β-oxidation of palmitoyl CoA (PCoA) in isolated heart mitochondria from Sham and streptozotocin (STZ)-induced type 1 diabetic (T1DM) guinea pigs (GPs). Parallel high throughput measurements of the rates of oxygen consumption (VO2) and hydrogen peroxide (H2O2) emission as a function of PCoA concentration, in the presence of L-carnitine and malate, were performed. We found that PCoA concentration < 200 nmol/mg mito protein resulted in low H2O2 emission flux, increasing thereafter in Sham and T1DM GPs under both states 4 and 3 respiration with diabetic mitochondria releasing higher amounts of ROS. Respiratory uncoupling and ROS excess occurred at PCoA > 600 nmol/mg mito prot, in both control and diabetic animals. Also, for the first time, we show that an integrated two compartment mitochondrial model of β-oxidation of long-chain fatty acids and main energy-redox processes is able to simulate the relationship between VO2 and H2O2 emission as a function of lipid concentration. Model and experimental results indicate that PCoA oxidation and its concentration-dependent uncoupling effect, together with a partial lipid-dependent decrease in the rate of superoxide generation, modulate H2O2 emission as a function of VO2. Results indicate that keeping low levels of intracellular lipid is crucial for mitochondria and cells to maintain ROS within physiological levels compatible with signaling and reliable energy supply.

Ameliorative properties of Iranian Trigonella foenum-graecum L. seeds and Punica granatum L. peel extracts in streptozotocin-induced experimental diabetic guinea pigs

ObjectiveTo assess the ameliorative properties of Iranian Trigonella foenum-graecum L. (T. foenum-graecum) seeds and Punica granatum L. (P. granatum) peel extracts against streptozotocin-induced diabetes in male guinea pigs. MethodsSixty guinea pigs were divided into six groups (10 guinea pigs per group). Group 1 consisted of normal animals. Groups 2 and 3 were treated with Iranian T. foenum-graecum seeds and P. granatum peel extract alone, respectively. Group 4 was treated with streptozotocin only; whereas Groups 5 and 6 receiving streptozotocin were treated with Iranian T. foenum-graecum seeds and P. granatum peel extract, respectively. All animals were treated for 30 days, and the body weight, blood and liver biochemical parameters were measured. ResultsGuinea pigs exposed to streptozotocin showed an alteration in body weight gain, fasting glucose level, kidney function parameters (blood urea nitrogen and creatinine) as well as decreased serum and hepatic total protein level. In addition, it increased the cholesterol and triglyceride level, while decreasing the hepatic glucose-6 phosphate dehydrogenase activity, glycogen, glutathione content and hepatic catalase activity. Oral treatment with T. foenum-graecum seeds and P. granatum peel extracts revealed significant protective properties with respect to body weight gain and other biochemical parameters studied. ConclusionsThe Iranian T. foenum-graecum seeds and P. granatum peel extracts are significantly potent in ameliorating diabetic condition induced by streptozotocin and improving various biochemical parameters in serum and liver of guinea pigs.

Deterioration of epithelium mediated mechanisms in diabetic-antigen sensitized airways of guinea pigs.

BackgroundThe onset of diabetes causes disruption of respiratory epithelial mediators. The present study investigates whether diabetes modifies the epithelium mediated bronchial responses in hyper-reactive airway smooth muscle (ASM) primarily through nitric oxide (NO), cyclooxygenase (COX), and epithelium derived hyperpolarizing factor (EpDHF) pathways.MethodsExperimental model of guinea pigs having hyper-reactive airways with or without diabetes were developed. The responses of tracheal rings to cumulative concentrations of acetylcholine (ACh) and isoproterenol (IP) in the presence and absence of epithelium and before and after incubation with NO, K+ATP and COX inhibitors, N-(ω)-Nitro-L-arginine methyl ester (L-NAME; 100 µM), glybenclamide (10 µM) and indomethacin (100 µM) were assessed.ResultsIn diabetic guinea pigs with hyper-reactive airways, a decrease in ACh induced bronchoconstriction was observed after epithelium removal and after incubation with L-NAME/indomethacin, suggesting damage to NO/COX pathways. Hyper-reactivity did not alter the response of trachea to ACh but affected the response to IP which was further reduced in hyper-reactive animals with diabetes. The ASM response to IP after glybenclamide treatment did not alter in hyper-reactive guinea pigs and diabetic guinea pigs with hyper-reactive airways, suggesting damage to the EpDHF pathway. Treatment with indomethacin reduced IP response in the hyper-reactive model, and did not produce any change in diabetic model with hyper-reactive airways, indicating further disruption of the COX pathway.ConclusionEpDHF pathway is damaged in hyper-reactive guinea pigs and in diabetic guinea pigs with hyper-reactive airways. Diabetes further aggravates the NO and COX mediated pathways in diabetic guinea pigs with hyper-reactive airways.

Influence of high myopia on expression of vascular endothelial growth factor and pigment epithelial derived factor in retina in diabetic guinea pig

Background Diabetic retinopathy (DR) seems to be rarely found in high myopia patients with diabetes mellitus.This finding suggests that myopia,especially high myopia,plays a protective effect against DR.It is well-known that the primary pathological base of DR is neovescularization,and the changes of vascular endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF) are associated with DR.Objective This study was to analyze the expressions of VEGF and PEDF in retina and investigate the influence of high myopia on the pathogenesis of DR.Methods Forty-eight 3-day-old guinea pigs were randomly divided into normal control group,high myopia group,diabetic group and diabetes with high myopia group.Translucent goggles were worn in the right eyes of the guinea pigs for consecutive 8 weeks to induce high myopia,and streptozocin (STZ) was intraperitoneally injected at a dose of 60 mg/kg for four times,every three days for once,to establish diabetic models in the corresponding groups.Twelve weeks after modeling,the animals were sacrificed by excessive anesthesia,and the retinas were isolated for the histopathological examination.Expressions of VEGF and PEDF in the retinas were detected by immunohistochemistry.The use and care of experimental animals conformed to Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.Results The diopter of the normal control group,high myopia group,diabetic group and diabetes with high myopia group were (+0.25±0.07),(-7.50±0.04),(+0.25±0.03) and (-7.50±0.02) D,the fasting glucose of the four groups were (5.3 ±0.1),(5.1 ±0.2),(19.7 ±0.4) and (18.5±0.3)mmol/L,respectively.Compared with the normal control group,the retinas of high myopia group were thin,and the ganglion cells were less.The retinas of diabetic group were loose and oedematous.The retinas of diabetes with high myopia group were thin and oedematous.The expressing level of VEGF in retinas (absorbance value,A) were 128.61 ±5.57,118.24±2.59,155.60±9.70 and 135.15±5.22 in the normal control group,high myopia group,diabetic group and diabetes with high myopia group,respectively,showing a significant difference among the groups (F=17.365,P=0.032),and the VEGF level was significantly lower in the diabetes with high myopia group than that of the diabetic group (t =5.210,P＜0.05).The expressing level of PEDF in retinas (A value) were 145.57± 8.35,149.54±6.20,127.71±2.45 and 137.53±7.38,in the normal control group,high myopia group,diabetic group and diabetes with high myopia group,respectively,with a statistically significant difference among the four groups (F =19.210,P =0.019),and the PEDF level was significantly higher in the diabetes with high myopia group than that of the diabetic group (t=4.521,P＜0.05).Conclusions The expression of VEGF is downregulated and PEDF is upregulated in the retinas of diabetes with high myopia guinea pigs,which may be an accountable mechanism for the low incidence of DR in high myopia eyes. Key words: Diabetic retinopathy; High myopia; Vascular endothelial growth factor; Pigment epithelial derived factor

Increased Severity of Tuberculosis in Guinea Pigs with Type 2 Diabetes: A Model of Diabetes-Tuberculosis Comorbidity

Impaired glucose tolerance and type 2 diabetes were induced in guinea pigs to model the emerging comorbidity of Mycobacterium tuberculosis infection in diabetic patients. Type 2 diabetes mellitus was induced by low-dose streptozotocin in guinea pigs rendered glucose intolerant by first feeding a high-fat, high-carbohydrate diet before M. tuberculosis exposure. M. tuberculosis infection of diabetic guinea pigs resulted in severe and rapidly progressive tuberculosis (TB) with a shortened survival interval, more severe pulmonary and extrapulmonary pathology, and a higher bacterial burden compared with glucose-intolerant and nondiabetic controls. Compared with nondiabetics, diabetic guinea pigs with TB had an exacerbated proinflammatory response with more severe granulocytic inflammation and higher gene expression for the cytokines/chemokines interferon-γ, IL-17A, IL-8, and IL-10 in the lung and for interferon-γ, tumor necrosis factor-α, IL-8, and monocyte chemoattractant protein-1 in the spleen. TB disease progression in guinea pigs with impaired glucose tolerance was similar to that of nondiabetic controls in the early stages of infection but was more severe by day 90. The guinea pig model of type 2 diabetes-TB comorbidity mimics important features of the naturally occurring disease in humans. This model will be beneficial in understanding the complex pathogenesis of TB in diabetic patients and to test new strategies to improve TB and diabetes control when the two diseases occur together.

Increased Small Dense LDL and Decreased Paraoxonase Enzyme Activity Reveals Formation of an Atherogenic Risk in Streptozotocin-Induced Diabetic Guinea Pigs

This study aimed to investigate LDL subfraction distribution as well as serum cholesteryl ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), and paraoxonase (PON1) activity in streptozotocin-induced diabetic guinea pigs. Materials/Methods. Guinea pigs were given a single intraperitoneal (ip) injection of streptozotocin (STZ) and animals having fasting blood glucose levels greater than 200 mg/dl, were considered diabetic. Protein levels of LCAT and CETP were determined via ELISA. Paraoxonase activity was measured kinetically by the formation of phenol while LDL subfraction analysis was done by disc polyacrylamide gel electrophoresis. Results. Plasma glucose and high-density lipoprotein (HDL) cholesterol were significantly increased while total cholesterol and LDL cholesterol were significantly decreased in diabetic guinea pigs compared to controls. LDL subfraction analysis revealed a significant decrease in nonatherogenic LDL-2 subfraction and a significant increase in atherogenic LDL-4 subfraction in diabetic guinea pigs compared to controls. Plasma CETP and PON1 levels were significantly decreased while LCAT showed no significant difference in diabetic guinea pigs compared to controls. Conclusion. Decreased non-atherogenic LDL-1, LDL-2 subfractions, increased small dense LDL-4 subfraction, and decreased PON1 activity, reveals formation of an atherogenic risk in diabetic guinea pigs. Decrease in CETP levels supports the observed increase in HDL cholesterol levels in diabetic guinea pigs.

Influence of Esomeprazole on the Pharmacokinetic and Pharmacodynamic Properties of Glipizide in Normal and Diabetic Guinea Pigs

Influence of Esomeprazole on the Pharmacokinetic and Pharmacodynamic Properties of Glipizide in Normal and Diabetic Guinea Pigs

Increased Small Dense LDL and Decreased Paraoxonase Enzyme Activity Reveals Formation of an Atherogenic Profile in Type 1 Diabetic Guinea Pigs

Increased Small Dense LDL and Decreased Paraoxonase Enzyme Activity Reveals Formation of an Atherogenic Profile in Type 1 Diabetic Guinea Pigs

Enhanced nerve‐stimulated muscarinic and neurokinin contractions of ileum from streptozotocin guinea‐pigs

Diabetes mellitus can lead to neuropathy of enteric neurons, resulting in abnormal gut motility. These studies investigated voltage-dependent contributions of muscarinic M₃ receptor activation by acetylcholine and neurokinin NK₁ receptor activation by neurokinins to nerve-stimulated contractions of longitudinal ileal strips from STZ guinea-pigs, a type 1 diabetic model with insulin deficiency, but mild hyperglycaemia. Contractions to bethanechol, substance P methyl ester, and nerve stimulation were greater in diabetic as compared to control ileum. The muscarinic M₃ receptor antagonist 4-DAMP at lower voltages and the neurokinin NK₁ receptor antagonist SR140333 at higher voltages, but not the neurokinin NK₁ receptor antagonist CP-96,345, were more effective at inhibiting nerve-stimulated immediate peak contractions and total areas of contraction of ileum from diabetic as compared to control animals. For diabetic ileum, voltage-dependent increases in the areas of nerve-stimulated contraction were observed in the presence of 4-DAMP and CP-96,345 but not SR140333. At low voltages only, nerve-stimulated release of acetylcholine was greater from diabetic as compared to control ileum. Fluorescence intensity of tachykinin-like immunoreactivity was increased in ileal myenteric ganglia from diabetic as compared to control animals. In diabetic guinea-pigs, stronger ileal nerve-stimulated contractions reflected increased release of acetylcholine at lower voltages and tachykinins at higher voltages, as well as increased sensitivity of smooth muscle M₃ and NK₁ receptors to acetylcholine and tachykinins. Hypoinsulinaemia may be a primary contributor to intestinal motility dysfunction in type 1 diabetes mellitus.

Prokinetic effects of ghrelin in streptozotocin-induced diabetic guinea pigs

was measured. Percentage of gastric emptying (GE%), intestinal transit (IT%), and colonic transit (CT%) were calculated. We found significantly delayed GE, IT, and CT in the diabetic guinea pigs compared with the control guinea pigs (P < 0.05); ghrelin improved both GE and IT, but not CT in the diabetic guinea pigs; the most effective dose of ghrelin was 100 μg/kg, and atropine blocked the prokinetic effects of ghrelin on GE and IT. These results are potentially significant for the clinical treatment of the delayed gastrointestinal transit in diabetes mellitus. In conclusion, ghrelin accelerates delayed GE and IT, but has no effect on CT in the diabetic guinea pigs. The prokinetic effects of ghrelin are probably exerted via the cholinergic pathway in the enteric nervous system. Ghrelin may have a therapeutic potential for diabetic patients with delayed upper gastrointestinal transit.

Physiological studies on the effect of a bradykinin potentiating factor (BPF) isolated from scorpion venom on the burnt skin of alloxan-induced diabetic Guinea pigs.

It is well known that, Wound healing in the diabetes is enormous, growing problem and having cost Medicaid. Therefore, this study produces an exciting prospect, to improve diabetic burn healing, and evaluates the ability of a bradykinin potentiating factor (BPF) isolated from scorpion venom (Buthus occitanus) in treatment of burns in diabetic male Guinea pigs. Male Guinea pigs of approximate (550 g body weight each) were divided into five groups. In the normal group; Guinea pigs were interaperitoneally (i.p) injected with 100 µL saline solution. The second, served as control group which were injected with 100 µL saline solution then standard burns were obtained on the dorsal skin. The 3 rd , 4 th and 5 th groups were i.p. injected with (750 mg /kg, body weight) with a single dose of Alloxan, then standard burns were obtained, after that the 4 th group was treated by BPF in 100 µL saline solutions (1μg/gm. b. w.) topically and the 5 th group treated with BPF (1μg/gm. b. w.) topically and interperitonialy (1μg/gm. b. w. twice a week). Every group contains 20 animals and sacrificed at 15 and 30 days post-treatment by BPF (10 animals per each). The results are recorded after monitoring the CBC including (RBCs, WBCs, platelets, Hb content and HCT percentage), lipid profile including (total cholesterol (TC), triglyceride (TGs), high density lipoprotein (HDL), low density lipoprotein (LDL) and very low density lipoprotein (VLDL)) and the skin antioxidant status (catalase activity (CAT) and superoxide dismutase (SOD) and serum nitric oxide (NO) beside malondialdehyde (MDA) concentration were also monitored during the study compared to normal animals. Also serum glucose level was monitored. The recorded results declared that, the treatment with BPF has shown an ameliorative effect on burn healing in diabetic animals. These observations and investigations were the pacemaker for the hypothesized ameliorating activity of BPF in the present study.

Neostigmine-induced contraction and nitric oxide-induced relaxation of isolated ileum from STZ diabetic guinea pigs

Both delayed gastrointestinal transit and autonomic neuropathy have been documented in patients with diabetes mellitus. The mechanism of neostigmine, an agent that mimics release of acetylcholine from autonomic neurons by prokinetic agents, to contract smooth muscle, despite dysfunctional enteric neural pathways, was determined using isolated ilea from STZ-treated and control guinea pigs. Both bethanechol- and neostigmine-induced contractions were stronger in diabetic ileum. Bethanechol-induced contractions of control but not diabetic ileum were increased by low dose scopolamine suggesting reduced activation of presynaptic muscarinic autoreceptors in diabetic ileum. The muscarinic receptor antagonist 4-DAMP strongly, but the nicotinic receptor antagonist hexamethonium only weakly, reduced neostigmine-induced contractions of control and diabetic ilea. The amount of acetylcholine, inferred from tissue choline content, was increased in diabetic ileum. Nicotinic neural and noncholinergic postjunctional smooth muscle receptors contributed more strongly to neostigmine-induced contractions in diabetic than control ileum. Relaxation of diabetic ileum by exogenous nitric oxide generated from sodium nitroprusside was comparable to control ileum, but smooth muscle relaxation by l-arginine using neuronal nitric oxide synthase to generate nitric oxide was weaker in diabetic ileum with evidence for a role for inducible nitric oxide synthase. Despite autonomic neuropathy, neostigmine strongly contracted ileum from diabetic animals but by a different mechanism including stronger activation of postjunctional muscarinic receptors, greater synaptic acetylcholine, stronger activation of noncholinergic excitatory pathways, and weaker activation of inhibitory pathways. A selective medication targeting a specific neural pathway may more effectively treat disordered gastrointestinal transit in patients with diabetes mellitus.