Alloxan Diabetic Rats Research Articles

Effect of vildagliptin conjugated monometallic nanoparticles and bimetallic nanocomposites on diabetes-induced cognitive deficit

Oxidative stress is one of the major causes of different metabolic disorders, including diabetes, cardiovascular diseases, neurodegenerative diseases and cancers. Some metabolic disorders like diabetes mellitus leads to secondary complications after micro and macrovascular complications. Some of the most prevalent neurodegenerative diseases, like cognitive impairment and Alzheimer's disease, are found in chronic diabetic patients. The present study is designed to understand the mechanism of interconnection between diabetes mellitus and cognitive deficit using the alloxan model of diabetes-induced cognitive deficit in the rat model. The alloxan monohydrate produces reactive oxygen species, producing superoxide free radicals, hydrogen peroxide and hydroxyl radicals. The hydroxyl radicals ultimately cause the death of beta cells, causing diabetes. Hence, the correlation of oxidative stress and neurodegeneration in cognitive impairment is the trigger for this study. In the present study, we investigate the ameliorative effect of vildagliptin (VLD) and its conjugated nanoparticles against alloxan-associated brain damage due to oxidative stress. The gold (Au), selenium (Se) nanoparticles, and bimetallic (Se@Au) nanocomposites of VLD are synthesized and assessed for improvement in their brain availability. The in-vitro antioxidant evaluation of the VLD and nanoparticles is done using DPPH, ABTS, and FRAP assay. The memory-related neurobehavioral studies, in-vivo antioxidant studies, in-vivo biochemical studies, and histopathological examinations are evaluated in rat brains. The VLD and its nanoformulations exhibited in-vitro and in-vivo antioxidant properties significantly (p < 0.01). They reduced the activity of AChE and nitrite in the alloxan diabetic rats. The bimetallic Se@Au VLDNCs displayed a more protective effect than VLD, VLD–AuNPs, and VLD–SeNPs.

Assessment of antidiabetic activity of Zingiber officinale and Cajanus cajan leaf extracts in the alloxan-diabetic rats

Assessment of antidiabetic activity of Zingiber officinale and Cajanus cajan leaf extracts in the alloxan-diabetic rats

Hypoglycemic and hypolipidemic effects of Lippia origanoides Kunth in diabetic rats.

Diabetes mellitus is a metabolic disorder commonly associated with atherosclerosis. Plants with therapeutic potential, such as Lippia origanoides Kunth, emerge as effective alternatives for treating these diseases. Therefore, this work aims to analyze the antihyperglycemic and antidyslipidemic potential of the hydroalcoholic extract of Lippia origanoides Kunth (ELo) in alloxan-diabetic rats. Animals were treated orally: normal control, hyperglycemic control, positive control glibenclamide (5 mg/kg), and groups treated with ELo (75, 150, and 250 mg/kg). Preclinical evaluation of ELo showed hypoglycemic, hypolipidemic, hepatic, and renal protective effects. At all doses, ELo significantly reduced hyperglycemia, triglycerides, total cholesterol, low-density lipoprotein, atherogenic index, atherogenic coefficient, and cardiovascular risk index (p < .05). Elo at different doses promoted an increase in insulin release compared to untreated animals (p < .05) and showed α-glucosidase inhibitory activity (p < .05). Also, ELo (250 mg/kg group) showed maximum reduction of hyperglycemia, alanine transaminase, aspartate aminotransferase, malonaldehyde, and urea compared to the hyperglycemic and glibenclamide groups, and creatinine only compared to the hyperglycemic groups (p < .05). The promising action of ELo in the context of diabetes may be related to the synergistic action of flavonoid compounds identified in liquid chromatography, whose pharmacological capabilities have already been documented in previous studies. The mechanisms may be the stimulation of insulin release; the inhibitory activity of α-glucosidase; improving general clinical conditions; and the antioxidant effects of the extract. These findings pave the way for the future development of an herbal presentation of L. origanoides Kunth as a hypoglycemic and cardiovascular protector with a lipid-lowering effect.

Molecular Modeling, Synthesis, and Antihyperglycemic Activity of the New Benzimidazole Derivatives - Imidazoline Receptor Agonists.

The paper presents the results of a study on the first synthesized benzimidazole derivatives obtained from labile nature carboxylic acids. The synthesis conditions of these substances were studied, their structure was proved, and some components were found to have sugar-reducing activity on the model of alloxan diabetes in rats. The study used molecular modeling methods such as docking based on the evolutionary model (igemdock), RP_HPLC method to monitor the synthesis reaction, and 1H NMR and 13C NMR, and other methods of organic chemistry to confirm the structures of synthesized substances. The docking showed that the ursodeoxycholic acid benzimidazole derivatives have high tropics to all imidazoline receptor carriers (PDB ID: 2XCG, 2bk3, 3p0c, 1QH4). The ursodeoxycholic acid benzimidazole derivative and arginine and histidine benzimidazole derivatives showed the highest sugar-lowering activity in the experiment on alloxan-diabetic rats. For these derivatives, the difference in glucose levels of treated rats was significant against untreated control. Therefore, the new derivatives of benzimidazole and labile natural organic acids can be used to create new classes of imidazoline receptor inhibitors for the treatment of diabetes mellitus and hypertension.

Effectiveness of durian peel ethanol extract for lowering blood sugar levels in alloxan diabetic wistar rats

High blood sugar levels can be influenced by several factors, including high-carbohydrate food consumption and a lack of physical activity. To minimize the side effects of hyperglycemic treatment, efforts have been made to explore anti-hyperglycemic compounds from other sources, such as durian peel (Durio zibetthinus Murr.). This study aimed to determine the effectiveness of ethanol extract from durian peel in lowering alloxan-induced blood sugar levels in Wistar rats (Rattus novergicus). The study is an experimental research employing an alloxan-induced diabetic rat model. The rats were divided into five different groups: Group I (negative control), Group II (positive control), Group III (dose 25 × 10–30/gBW), Group IV (dose 50 × 10–30/gBW), and Group V (dose 100 × 10–30/gBW). The durian peel used in this study was extracted using the maceration method with ethanol as the solvent. The results of this study indicate that ethanol extract from durian peel significantly reduced blood sugar levels after 10 to 15 days of durian peel extract administration (p &lt; 0.05).

Study of changes in the activity levels of purine nucleoside phosphorylase and the role of nitric oxide in the development of pathology in alloxan-diabetic rats

The problem of treating diabetes mellitus has not been resolved to this day; it requires a detailed study of various links of pathogenesis at the molecular level. In diabetes, conditions arise for the formation of oxidative stress. Diabetes mellitus is associated with the early development of cardiovascular complications, the immune e system is destroyed. Endothelial cells produce nitric oxide (NO), a substance that is able to maintain a balance of vascular tone, coagulation and inflammation. Purine nucleoside phosphorylase (PNP) is one of the most important enzymes of purine metabolism, which characterizes the immune status of the organism. The aim of this study was to study the enzymatic activity of PNP, as well as to determine the levels of nitric oxide in the blood serum, liver and pancreas in albino rats with simulated alloxan diabetes. The results of our studies on the detection of changes in the activity of PNP in the pancreas on the model of alloxandiabetic rats showed that at the late stage, the activity of PNP in the pancreas is completely suppressed, which indicates significant changes in the immune status of the body, the content of nitric oxide increases. Understanding the complex metabolic disorders that interact with the NO system may provide us with additional therapeutic options to reduce cardiovascular morbidity and mortality in diabetes mellitus. Indicators of NO and PNP can be used as additional paraclinical indicators for early diagnosis and to identify and clarify the degree of activity of the pathological process, the nature of the course, the stage of the disease, which contributes to the appointment of individualized adequate therapy.

Antidiabetic effect of black pepper, turmeric, and ajwa date pulp, seed, and their mixtures as antioxidants in alloxan diabetic rats

Antidiabetic effect of black pepper, turmeric, and ajwa date pulp, seed, and their mixtures as antioxidants in alloxan diabetic rats

Determination of Hypoglycemic, Hypolipidemic and Nephroprotective Effects of Berberis Calliobotrys in Alloxan-Induced Diabetic Rats.

Many plants of the Berberis genus have been reported pharmacologically to possess anti-diabetic potential, and Berberis calliobotrys has been found to be an inhibitor of α-glucosidase, α-amylase and tyrosinase. Thus, this study investigated the hypoglycemic effects of Berberis calliobotrys methanol extract/fractions using in vitro and In vivo methods. Bovine serum albumin (BSA), BSA-methylglyoxal and BSA-glucose methods were used to assess anti-glycation activity in vitro, while in vivo hypoglycemic effects were determined by oral glucose tolerance test (OGTT). Moreover, the hypolipidemic and nephroprotective effects were studied and phenolics were detected using high performance liquid chromatography (HPLC). In vitro anti-glycation showed a significant reduction in glycated end-products formation at 1, 0.25 and 0.5 mg/mL. In vivo hypoglycemic effects were tested at 200, 400 and 600 mg/kg by measuring blood glucose, insulin, hemoglobin (Hb) and HbA1c. The synergistic effect of extract/fractions (600 mg/kg) with insulin exhibited a pronounced glucose reduction in alloxan diabetic rats. The oral glucose tolerance test (OGTT) demonstrated a decline in glucose concentration. Moreover, extract/fractions (600 mg/kg) exhibited an improved lipid profile, increased Hb, HbA1c levels and body weight for 30 days. Furthermore, diabetic animals significantly exhibited an upsurge in total protein, albumin and globulin levels, along with a significant improvement in urea and creatinine after extract/fractions administration for 42 days. Phytochemistry revealed alkaloids, tannins, glycosides, flavonoids, phenols, terpenoids and saponins. HPLC showed the presence of phenolics in ethyl acetate fraction that could be accountable for pharmacological actions. Therefore, it can be concluded that Berberis calliobotrys possesses strong hypoglycemic, hypolipidemic and nephroprotective effects, and could be a potential therapeutic agent for diabetes treatment.

Renal Sympathetic Hyperactivity in Diabetes Is Modulated by 5-HT1D Receptor Activation via NO Pathway.

Renal vasculature, which is highly innervated by sympathetic fibers, contributes to cardiovascular homeostasis. This renal sympathetic outflow is inhibited by 5-HT in normoglycaemic rats. Considering that diabetes induces cardiovascular complications, we aimed to determine whether diabetic state modifies noradrenergic input at renal level and its serotonergic modulation in rats. Alloxan diabetic rats were anaesthetized (pentobarbital; 60 mg/kg i.p.) and prepared for in situ autoperfusion of the left kidney to continuously measure systemic blood pressure (SBP), heart rate (HR), and renal perfusion pressure (RPP). Electrical stimulation of renal sympathetic outflow induces frequency-dependent increases (Δ) in RPP (23.9 ± 2.1, 59.5 ± 1.9, and 80.5 ± 3.5 mm Hg at 2, 4, and 6 Hz, respectively), which were higher than in normoglycaemic rats, without modifying HR or SBP. Intraarterial bolus of 5-HT and 5-CT (5-HT1/5/7 agonist) reduced electrically induced ΔRPP. Only L-694,247 (5-HT1D agonist) reproduced 5-CT inhibition on sympathetic-induced vasoconstrictions, whereas it did not modify exogenous noradrenaline-induced ΔRPP. 5-CT inhibition was exclusively abolished by i.v. bolus of LY310762 (5-HT1D antagonist). An inhibitor of guanylyl cyclase, ODQ (i.v.), completely reversed the L-694,247 inhibitory effect. In conclusion, diabetes induces an enhancement in sympathetic-induced vasopressor responses at the renal level. Prejunctional 5-HT1D receptors, via the nitric oxide pathway, inhibit noradrenergic-induced vasoconstrictions in diabetic rats.

Antioxidant properties of date seeds extract (Phoenix dactylifera L.) in alloxan induced damage in rats.

The study was conducted to examine the antioxidant activity and evaluate the protective effects of the date seeds powder kentichi against alloxan-induced damage in the liver, kidney, and pancreas in diabetic's rats. Group 1: control group, that did not receive any treatment, Group 2: alloxan was injected intraperitoneally (120 mg/kg body weight) for two days (Diab), Group 3: treated only by date seeds powder added in the diet (300 g/kg) for 6 weeks (DSPK), Group 4: alloxan-diabetic rats treated with date seeds powder (300 g/kg) (DSPK + Diab). Estimations of biochemical parameters in blood were determined. TBARS, SOD, CAT, and GPx activities were determined. A histopathological study was done by immersing pieces of both organs in a fixative solution followed by paraffin hematoxylin-eosin staining. In addition, the antioxidant activities of DSPK were evaluated by DPPH radical scavenging activity, reducing power, and ABTS free radical scavenging. The results revealed that date seeds significantly decreased serum levels of glucose, cholesterol, triglycerides, urea, creatinine, T-protein, ALP, D-bili and T-bili levels. In addition, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities that had been reduced in liver, kidney, and pancreas of the treated group were restored by DSPK treatments and, therefore, the lipid peroxidation level was reduced in the liver, kidney and pancreas tissue compared to the control group. Additionally, the histological structure in these organs was restored after treatment with date seeds powder.

Osmotic concentration of urine in the dynamics of the development of alloxan-induced experimental diabetes

In order to clarify the peculiarities of the osmotic concentration of urine in the dynamics of the development of alloxan-induced experimental diabetes mellitus (DDM), studies were conducted on 54 sexually mature non-linear male white rats, in which DDM was simulated by a single intraperitoneal injection of alloxan solution (Alloxan monohydrate, "Acros Organics", Belgium) at a dose of 160 mg/kg of body weight after a previous 12-hour food deprivation with preserved access to water. 10, 25, and 45 days after the introduction of the diabetogenic substance, 24 alloxan-diabetic rats, as well as 30 control (intact) animals, were loading with tap water in a volume of 5% of body weight, urine was collected for 2 hours, euthanasia was performed by decapitation under light ether anesthesia. In blood samples, the level of glucose and creatinine was determined, in urine samples, after evaluating the water-induced 2-hour diuresis (in ml/100 g of body weight in 2 hours), the concentration of creatinine was determined, the clearance of endogenous creatinine, the clearance of osmotically free water, as well as relative (tubular) reabsorption of water, determined the content of glucose, urea, its excretion, including per 100 μl of glomerular filtrate, as well as urine osmolarity. The results of the study allow us to state that as the duration of experimental diabetes is prolonged, the pathogenetic significance of hyperfiltration, which determines the speed of fluid movement along the tubule and the intensity of its absorption, weakens in relation to the processes of osmotic concentration of urine, yielding to other factors, such as the osmolarity of the medulla of the kidneys, as well as the presence of substances in the liquid of the distal segment and collecting tubes, the reabsorption of which can change their concentration in the collecting tubes as the urine progresses. In diabetes, in addition to glucose, such substances include urea. Attempts to analyze the renal excretion of urea revealed that changes in its urinary concentration are definitely correlated with the dynamics of changes in urine osmolality. Moreover, it can be assumed that urea transport disorders in the diabetic kidney occur earlier than the ability to excrete osmotically active substances in general. A joint study of the processes of renal transport of urea and urine osmolarity can serve as an early verifier of tubulointerstitial damage. Nevertheless, to increase the reliability of the interpretation of the features of the osmotic concentration of urine in diabetes, we consider it necessary to study the nature of the renal transport of electrolytes (sodium, potassium, calcium, and ammonium).

Oxidative stress and changes in liver sialoglycoconjugate metabolic parameters in rats with alloxanic diabetes mellitus

BACKGROUND: Oxidative stress may be one of the mechanisms for the development of complications in DM and many forms of CKD. However, the influence of this factor on the metabolism of sialoglycoconjugates, which actively participates in the regulatory processes of the body, is unknown.AIM: comparative study of the effect of lipoic acid on the parameters of liver sialoglycoconjugate metabolism in rats with alloxan diabetes mellitus.MATERIALS AND METHODS: Studies were conducted on white male rats weighing 180–220 grams. The animals were divided into three groups: in the animals of the first and second groups, alloxan diabetes mellitus (DM) was caused by a single subcutaneous injection of alloxan tetrahydrate (AT). Animals of the second group received lipoic acid intramuscularly; the third group consisted of intact rats. On 5, 10, 20, 30 and 40 days after the injection of AT, a comprehensive examination of the animal’s condition was performed: 1) determination of the level of glycemia; 2) assessment of the degree of development of oxidative stress by the content of TBK-active products in the liver; 3) study of the dynamics of the exchange of sialoglycoconjugates in the liver (free, oligo-and protein-bound sialic acids, sialidase activity).RESULTS: The study was conducted on 106 rats, each experimental group had 48 animals, control — 10. It was found that the administration of α-lipoic acid to rats with alloxan diabetes leads to a decrease in the level of glycemia. The introduction of lipoic acid in experimental animals did not reduce the sialidase activity and the content of all sialic acid fractions in the liver, although it reduced the degree of oxidative stress in the body.CONCLUSION: Supplementation of lipoic acid in experimental animals did not significantly decrease sialidase activity and content of the sialic acid fractions under study in the liver, although it did reduce the degree of oxidative stress development in the organism. The increased rate of sialic acid metabolism in the liver of alloxan-diabetic rats may indicate a restructuring of hepatocyte metabolism to adapt the whole organism to prolonged hyperglycemia under insulin deficiency conditions.

Effect of Poly-Herbal Formula (PHF5) on Hepatoprotective and Biochemical Parameters of Alloxan-Induced Diabetic Wistar Rats

Background: The current estimates by World Health Organization revealed that near 2030, the number of diabetic patients will reach up to 370 million in the world wide . It would be one of the most common degenerative illnesses in human beings in future that needs to seek urgent solution. Plants have been the major source of medicine since the ancient time.&#x0D; Purpose: This study evaluated the hepaprotective action of Ocimum gratissimum, Gnetum africanum, Gongronema latifolium, Vernonia amygdalina and Aloe Barbadensis leaf extracts and their effects on biochemical parameters of induced alloxan diabetic wister rats. Standard methods were used in the extraction process.&#x0D; Methods: Thirty (30) male Wistar rats weighing (80_120) grams were obtained and they were kept in animal house to acclimatize for two weeks prior to the experiment. The rats were divided into six groups containing five rats each. Group 1 served as normal control, group 2 had the diabetic rats treated with PHF5 (75 mg/kg bodyweight); group 3 contained diabetic rats treated with PHF5 (150 mg/kg bodyweight); group 4 contained diabetic rats treated with PHF5 (300 mg/kg bodyweight); group 5 had diabetic rats not given any intervention, group 6 contained diabetic rats treated with Glibenclamide (5 mg/kg bodyweight). The rats were induced via intra peritoneal by using alloxan monohydrate (100 mg/kg bodyweight). Extracts of PHF5 were administered to the rats orally for eight weeks, after which rats were sacrificed by cervical dislocation under light ether anaesthesia. Blood was collected for biochemical evaluation using standard techniques (Randox kits). Fasting blood glucose level was checked weekly.&#x0D; Results: Acute toxicity studies of PHF5 revealed no toxicity to the animals that received the PHF5 dose up to 1000 mg/kg bodyweight. The increased liver (Aspartate amino transferase, Alanine Transferase and Alkaline Phosphatase) marker enzymes in the diabetic rats were significantly (p&lt;0.05) lowered in the PHF5 treated rats and found to be within the normal range while total protein was significantly higher showed no effect on the liver total protein.&#x0D; Conclusion: It is concluded that this study suggest that treating alloxan induced diabetic rats with poly herbal formulated (PHF5); Ocimum gratissimum, Gnetum africanum, Gongronema latifolium, Vernonia amygdalina, and Aloe Barbadensis leaf extracts in different doses of mg/kg enhanced hepaprotective protection against body damage.

Synthesis, physico-chemical properties and effect of adenosine thiamine triphosphate on vitamin B1 metabolism in the liver of alloxan diabetic rats

BackgroundAdenosine thiamine triphosphate (AThTP) is a nucleotide discovered in bacteria and some other living organisms more than a decade ago. No biochemical function for AThTP has been established yet, however, experimental data available indicate its possible involvement in metabolic regulation or cell signaling. Metabolism of AThTP in mammals, as well as the feasibility of its pharmacological application, is essentially unstudied. MethodsPreparative low-pressure chromatography was employed to purify chemically synthesized AThTP with its further analysis by mass spectrometry, HPLC, UV and fluorescence spectroscopy. Enzyme activity assays along with HPLC were used to examine the effects of AThTP and thiamine on vitamin B1 metabolism in the liver of alloxan-induced diabetic rats. ResultsAn improved procedure for AThTP synthesis and purification is elaborated. Solution stability, optical spectral properties and the molar absorption coefficient for AThTP were determined. The levels of thiamine compounds were found to be increased in the liver of diabetic rats. Neither AThTP nor thiamine treatment affected hepatic vitamin B1 metabolism. Fasting blood glucose concentration was also unchangeable after AThTP or thiamine administration. General significanceContrast to the widespread view about thiamine deficiency in diabetes, our results clearly shows an adaptive increase in the level of B1 vitamers in the liver of alloxan diabetic rats with no further rising after AThTP or thiamine treatment at a moderate dose. Neither AThTP nor thiamine is effective in glycaemic control. These findings are to be considered in future studies dealing with thiamine or its analogues application to correct metabolic disturbances in diabetes.

Ammodaucus leucotrichus Coss. &amp; Durieu: Antihyperglycemic activity via the inhibition of α-amylase, α-glucosidase, and intestinal glucose absorption activities and its chemical composition

Context: Ammodaucus leucotrichus commonly known as a ‘Kamune es sufi or akâman’ in Morocco, is used to treat many diseases including diabetes. Aims: To investigate the antihyperglycemic activity of an aqueous extract of fruits A. leucotrichus (AEAL) and its chemical composition. Methods: The antihyperglycemic effect of the AEAL was tested against intestinal α-glucosidase and pancreatic α-amylase activities, in vitro, at the concentrations (41-328 µg/mL) and (0.5-3 mg/mL) respectively. In addition, the inhibitory effect of the AEAL (150 mg/kg) against these enzymes was confirmed, in vivo in normal and alloxan diabetic rats using sucrose, starch, and glucose as a substrate.The antihyperglycemic effect of the AEAL was also tested against intestinal D-glucose absorption activity at the dose of 150 mg/kg using the jejunum segment perfusion technique, in situ. Chemical composition was evaluated using HPLC. Results: The results of this study showed that the AEAL was significantly (p&lt;0.001) inhibited the intestinal α-glucosidase, in vitro (IC50 = 0.254 mg/mL). The same effect of this extract was confirmed against the pancreatic α-amylase activity, with IC50 = 1.81 mg/mL. In vivo, the oral intake of the AEAL at a dose of 150 mg/kg was significantly attenuated the hyperglycemia induced by the sucrose, starch, and glucose in the normal and alloxan diabetic rats. AEAL, also, significantly (p&lt;0.01) decreased intestinal glucose absorption, in situ.HPLC results revealed the presence of four molecules: vanillin, quercetin, kaempferol, and thymol. Conclusions: A. leucotrichus showed a significant antihyperglycemic activity. This effect can be explained by the inhibition of α-amylase, α-glucosidase activities, and the intestinal absorption of D-glucose.

HPLC PROFILING AND ANTIHYPERGLYCEMIC EVALUATION OF PHE (POLYHERBAL EXTRACT) OF SELECTED INDIAN MEDICINAL HERBS IN ALLOXAN DIABETIC RATS

In the present work antihyperglycemic screening of the polyherbal powder was carried out by oral administration of an aqueous extract of polyherbal powder on alloxan-induced diabetic rats. The polyherbal powder displayed a substantial increase in hypoglycemic efficacy at a dose of 100 mg/kg and 200 mg/kg in both Alloxan-induced diabetic rats and normal rats. The powder also exhibited enhancement in various parameters like the glycogen content of the liver, restoration of pancreatic β-cells, body weight, and carbohydrate metabolizing enzymes. Results obtained showed that the Alloxan diabetic rats on treatment with polyherbal powder at various doses of 100 mg/kg and 200 mg/kg considerably improved their body weights to 222.30 ± 3.42 g and 221.6 ± 3.60 g when compared to non-diabetic rats respectively. In addition to this, the histopathological analysis demonstrated that polyherbal powder enhanced the histological architecture of the islets of Langerhans significantly which is on par when compared to the standard Glibenclamide

Augmentation of the Diabetic Wound Healing Properties Following Topical Sesame Oil and Chlorine Dioxide Jel Applications in Albino Rats

Diabetic wound healing impairment remains a major problem in diabetic patients. Medical plants and new products are subjected to have a powerful pharmacological treatment modality on wound healing as sesame oil and Chlorine dioxide gel. Herein, we assessed the contribution of both topical sesame oil and chlorine dioxide gel application on the early healing process of full-thickness wounds in alloxan diabetic rat models. A full-thickness (8mm) artificial uniform skin wounds were created in alloxan-induced diabetic rats (100mg/kg b.w.). Rats were randomly divided into four groups: groups treated with sesame oil and chlorine dioxide gel, non-treated groups served as control non-diabetic, and control diabetic non-treated. Antioxidant activity was evaluated, post healing biopsies were histopathologically and immunohistochemically assessed in addition to measuring inflammatory mediators (TNF-α) by PCR. We found higher blood glucose levels, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea, serum creatinine, and nitric oxide (NO) levels in diabetic groups in comparison to control non-diabetic ones. Low total protein and superoxidase dismutase (SOD) levels in control diabetic non-treated rats than the control nondiabetic and treated groups. A higher level of malondialdehyde (MDA) was detected in the control diabetic group compared to the other treated and control non-diabetic group. Treated wounds showed better contraction percentage, granulation tissue formation, tissue regeneration and lower inflammatory mediator level (TNF-α) compared to control diabetic un-treated wounds. Sesame oil and chlorine dioxide gel applications are able to accelerate wound healing activity in diabetic rats.

INFLUENCE OF MELATONIN ON AGE-RELATED CHANGES IN CARBOHYDRATE METABOLISM AND ANTIOXIDANT CAPACITY IN THE BLOOD OF ALLOXAN DIABETIC RATS

Melatonin and its metabolites have potent antioxidant/anti-inflammatory properties, and they have proven to be highly effective in a variety of disorders linked to inflammation and oxidative stress. The object of this experimental research was to ascertain the influence of aging on the level of basal glycemia and activities of glucose-6-phosphate dehydrogenase [EC1.1.1.49], pyruvate kinase [EC 2.7.1.40] and glutathione reductase [EC1.6.4.2] in erythrocytes of alloxan diabetic rats on the background of melatonin injections. Methods: We used 100 male Wistar rats, two age groups: the - 2-month (adult), and II - 4-month (old). Alloxan diabetes was evoked via injecting the rats with a 5% solution of alloxan monohydrate intraperitoneally in a dose of 170 mg/kg. Four days after diabetes induction, rats were divided into diabetic (untreated) and melatonin-diabetic group (10 mg/kg, daily and intraperitoneally for six weeks). Blood was taken from the tail vein evaluate the basal glycemia on 5-th and 47-th day after the injection of alloxan. Rats were sacrificed at the 47-th day of the experiment accordance with the ethical treatment of animals. Determinations of the enzymes activities were by standard methods. Statistical analysis was performed using Statistica 10 StatSoft Inc. Results. The level of basal glycemia on the fifth day of the experiment in animals of both groups increased on average by 115% from baseline values. We founded that on 47-th day this index was higher in group of old rats on 20% more than in adult rats. Pyruvate kinase activity in erythrocytes of adult and old animals with diabetes decreased by 34% and 51% respectively compared with the control. glucose-6-phosphate dehydrogenase activity in erythrocytes of adult and old animals with diabetes decreased by 25% and 44% respectively compared with the control on 47-th day. The changes may be the result of age-related disorders of glucose metabolism due to disturbances in free radical mechanisms. Glutathione reductase activity in erythrocytes of adult and old animals with diabetes decreased by 30% and 36% respectively compared with the control on 47-th day. A 42-days injection of melatonin to the alloxan diabetic rats of both groups contributed to a normalization of the level of basal glycemia, the activities of pyruvate kinase and glutathione reductase in the rat blood, as well as to a considerable increase of the activity of glucose-6-phosphate dehydrogenase, whose level exceeded by average 9% this particular index in the control group of animals. Under the influence of melatonin increase activity of glucose-6-phosphate dehydrogenase in the blood of rats may be due to the increasing number of substrate for glucose-6-phosphate dehydrogenase (stimulating the flow of glucose into cells and its phosphorylation) and direct action. Conclusion. In this case melatonin probably increases use of glucose for regeneration of NADPH2 and aerobic oxidation of glucose that indicate an acceleration of antioxidative protection and energy production in blood of adult and old diabetic rats.

The “Levine effect” and the father of modern diabetes research

The “Levine effect” and the father of modern diabetes research

In vitro, acute and subchronic evaluation of the antidiabetic activity of Atractylis flava Desf n-butanol extract in alloxan-diabetic rats

BackgroundDiabetes mellitus is a serious complex multifactorial disorder that imposes huge health and economic burden on societies. Because the currently available medications have many drawbacks, it's important to look for alternative therapies. Medicinal plants utilized in folk medicine are ideal candidates. Therefore, this work assessed the antidiabetic action of n-butanol extract from the whole plant Atractylis flava Desf (BEAF). These ethnomedicinal properties of BEAF were scientifically validated using in vitro and in vivo assays. In vitro antidiabetic effect of the BEAF was conducted using α-Glucosidase and α-Amylase assays. While the antihyperglycemic activity was assessed using two rat models: Alloxan-induced diabetic rats and oral glucose challenged rats. Experimental diabetes was induced by a single intraperitoneal injection of alloxan at a dose of 150 mg/kg and animals with fasting blood glucose levels (BGL) > 200 mg/dL were considered diabetic. Glibenclamide (5 mg/kg) was used as a typical drug.ResultsThe BEAF at all tested dose levels (100, 250, and 500 mg/kg) showed a significant decrease in blood glucose level in all the two animal models. Besides, the plant extract exhibited a potent inhibitory effect on α-Amylase and α-Glucosidase activity at a concentration of 1000 µg/mL with 76.17% and 89.37%, respectively.ConclusionBEAF exerts in vitro and in vivo antidiabetic effects, these results suggest that the plant extract can be a therapeutic resource in the treatment of diabetes and hyperlipidemia.