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Physiological Research 2001Alloxan and streptozotocin are widely used to induce experimental diabetes in animals. The mechanism of their action in B cells of the pancreas has been intensively... (Review)
Review
Alloxan and streptozotocin are widely used to induce experimental diabetes in animals. The mechanism of their action in B cells of the pancreas has been intensively investigated and now is quite well understood. The cytotoxic action of both these diabetogenic agents is mediated by reactive oxygen species, however, the source of their generation is different in the case of alloxan and streptozotocin. Alloxan and the product of its reduction, dialuric acid, establish a redox cycle with the formation of superoxide radicals. These radicals undergo dismutation to hydrogen peroxide. Thereafter highly reactive hydroxyl radicals are formed by the Fenton reaction. The action of reactive oxygen species with a simultaneous massive increase in cytosolic calcium concentration causes rapid destruction of B cells. Streptozotocin enters the B cell via a glucose transporter (GLUT2) and causes alkylation of DNA. DNA damage induces activation of poly ADP-ribosylation, a process that is more important for the diabetogenicity of streptozotocin than DNA damage itself. Poly ADP-ribosylation leads to depletion of cellular NAD+ and ATP. Enhanced ATP dephosphorylation after streptozotocin treatment supplies a substrate for xanthine oxidase resulting in the formation of superoxide radicals. Consequently, hydrogen peroxide and hydroxyl radicals are also generated. Furthermore, streptozotocin liberates toxic amounts of nitric oxide that inhibits aconitase activity and participates in DNA damage. As a result of the streptozotocin action, B cells undergo the destruction by necrosis.
Topics: Alloxan; Animals; Antibiotics, Antineoplastic; Diabetes Mellitus, Experimental; Islets of Langerhans; Rats; Streptozocin
PubMed: 11829314
DOI: No ID Found -
Pharmaceutical Biology Dec 2021Lour. (Moraceae) is used for the treatment of different ailments, including diabetes, and requires scientific validation.
CONTEXT
Lour. (Moraceae) is used for the treatment of different ailments, including diabetes, and requires scientific validation.
OBJECTIVE
The study evaluates antidiabetic effects, antioxidant potential, and cytotoxicity of leaf and bark extracts of .
MATERIALS AND METHODS
Antidiabetic effects were assessed by inducing diabetes in Wistar albino rats ( = 5, six groups included 30 rats) by injecting alloxan [0.25 mg/kg body weight (bw)] intraperitoneally, and efficacy of methanol extracts of leaf and bark, and aqueous extract of leaves were evaluated by oral administration of 300 mg/kg bw of extracts for 3 weeks. Glibenclamide (Dibenol™) was used as a control (10 mg/kg bw). Antioxidant properties were examined by DPPH free radical scavenging activity, and cytotoxicity was investigated using a brine shrimp lethality assay.
RESULTS
Methanol extracts of leaves and bark, and the aqueous extract of leaves of , caused significant reductions in blood glucose levels in diabetic rats of 36.83, 70.33, and 52.71%, respectively, after 21 days of treatment. IC values in DPPH radical scavenging assessment for those extracts were 58.92, 88.54, and 111.36 µg/mL, respectively. LC values for brine shrimp lethality for the extracts were 173.80, 32.36, and 3235.9 µg/mL, respectively.
DISCUSSION AND CONCLUSIONS
The methanol bark extract of showed significant antidiabetic activity. This study will significantly contribute to establishing the plant as an alternative medicinal resource for rural populations of Bangladesh and provides an opportunity for further research to identify the primary active compound(s) and establish new drug candidates.
Topics: Alloxan; Animals; Antioxidants; Bangladesh; Blood Glucose; Diabetes Mellitus, Experimental; Glyburide; Hypoglycemic Agents; Models, Animal; Moraceae; Plant Bark; Plant Extracts; Rats; Rats, Wistar
PubMed: 34365913
DOI: 10.1080/13880209.2021.1954668 -
ACS Omega Feb 2022Alloxan is a chemical generally administered to rats to induce diabetes mellitus, and pharmaceutical industries test the efficacy of their diabetic products on these...
Alloxan is a chemical generally administered to rats to induce diabetes mellitus, and pharmaceutical industries test the efficacy of their diabetic products on these rats. Alloxan is in a redox cycle with dialuric acid; hence, direct estimation of alloxan may not represent the actual concentration of the same in a given matrix. Also, in recent times, alloxan is added to food materials, especially to the all-purpose flour (maida) to bring softness and white color to the flour. Hence, consumption of food items made from such flour could induce diabetic mellitus in individuals, making it imperative to develop an accurate estimation of alloxan in food items. Herein, a voltammetric-based technique is developed to quantify the alloxan in refined wheat flour (maida) using an unmodified glassy carbon electrode (GCE). The electrochemical method offers rapid sensing while the use of an unmodified GCE surface offers repeatability and reproducibility between measurements. First, alloxan is converted to its stable adduct alloxazine by the reaction with -phenylenediamine. The alloxazine adduct is electrochemically active, and the concentration of alloxan is estimated as a function of alloxazine formed using the voltammetric technique. The common shortfall in alloxan detection mainly involves its short half-life (∼a minute) whereas the alloxazine adduct formed is stable over a period of time. Using the current approach, alloxan concentration ranging from 10 to 600 μM is detected with a sensitivity of 0.0116 μA/μM. A low limit of detection of 1.95 μM with a precision of 1.2% is achieved using the above method. Real sample analysis revealed the presence of alloxan in all-purpose flour (maida-refined wheat flour) and bread purchased from the local market to the values of 35.76 and 25.03 μM, respectively. The same is confirmed using the gold-standard colorimetric technique.
PubMed: 35224361
DOI: 10.1021/acsomega.1c06313 -
BioMed Research International 2022Type 1 diabetes mellitus (T1DM) is a chronic disease represented by insulin-causing pancreatic -cell disruption and hyperglycemia. Therefore, it is necessary to...
Type 1 diabetes mellitus (T1DM) is a chronic disease represented by insulin-causing pancreatic -cell disruption and hyperglycemia. Therefore, it is necessary to establish a variety of animal models of diabetes to study the pathogenesis and pathophysiology of it. However, there are few reports on the use of beagle dogs to establish an animal model of type 1 diabetes. This study aimed to explore a simple and feasible modeling method to establish a long-term and stable type 1 diabetes model in beagle dogs. Forty adult beagle dogs were randomly divided into control group and model group. After 24 h of fasting, streptozotocin (20 mg/kg) and alloxan (20 mg/kg) were injected through the cephalic vein. The second intravenous injection was given on the 4th day after the first injection. Insulin release testing was performed on the 7th day after the last intravenous injection. Fasting blood glucose and body weight were recorded monthly. Four months after the last injection, the serum fructosamine content and the ratio of glycated hemoglobin were detected. Then, the pancreatic tissue was harvested for histopathological examination. The results showed that the level of fasting blood glucose of the 16 dogs in the model group was consistently higher than 11.1 mmol/L for 4 consecutive months. Moreover, compared with the control group, the insulin release curve of the model group was flat with no increase. The body weight of the model group was significantly reduced, and the ratios of blood glucose, fructosamine, and glycosylated hemoglobin were significantly higher than those in the control group. Meanwhile, histopathological examination of the pancreas showed that the islet beta cells appeared to have vacuoles or even necrosis. In the model group, pancreatic -cells were damaged and insulin release was reduced. These results suggest that the above modeling methods can induce long-term and stable type 1 diabetes models in beagle dogs.
Topics: Alloxan; Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Type 1; Dogs; Fructosamine; Insulin; Streptozocin
PubMed: 35978645
DOI: 10.1155/2022/5422287 -
Journal of Medicine and Life Mar 2022This study aimed to evaluate metformin as a widely used oral hypoglycemic agent and identify the effects on biochemical and antioxidant body systems of rabbits. Four...
This study aimed to evaluate metformin as a widely used oral hypoglycemic agent and identify the effects on biochemical and antioxidant body systems of rabbits. Four groups of rabbits were randomly allocated as the control, the alloxan-induced diabetic, metformin-treated, and alloxan treated with metformin. The results revealed that alloxan leads to significant elevation in glucose (Glc) levels, malondialdehyde (MDA), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), triglycerides (TGs), and total cholesterol (TCH), and a significant decline in high-density lipoprotein (HDL) and glutathione (GSH) as compared with the control group. Metformin alone caused a significant decline in Glc and HDL with significant elevation in LDL and MDA without significant changes in TCH, TGs, VLDL, and GSH. When metformin was offered as a treatment for alloxan-induced diabetic animals, it caused a significant decline in Glc, TCH, TGs, LDL, and VLDL levels with significant elevation in GSH and without a significant change in HDL and MDA. Metformin causes a decline in glucose levels due to its ability to decrease the use of substances hepatic cells use to create glucose and its ability to induce the enzymes participating in glucose oxidation.
Topics: Animals; Rabbits; Alloxan; Diabetes Mellitus, Experimental; Glutathione; Hypoglycemic Agents; Metformin
PubMed: 35450001
DOI: 10.25122/jml-2021-0417 -
Romanian Journal of Morphology and... 2022Vertebral abnormalities in offspring of diabetic mothers make major challenges worldwide and were not sufficiently studied before.
BACKGROUND
Vertebral abnormalities in offspring of diabetic mothers make major challenges worldwide and were not sufficiently studied before.
AIM
To investigate the effects of alloxan-induced diabetes on rats' lumbar vertebrae, and to assess the potential beneficial impact of arachidonic acid.
MATERIALS AND METHODS
Pregnant rats were randomly equally divided into four groups: control, alloxan-induced diabetes received alloxan injection 150 mg∕kg, alloxan + arachidonic acid group received arachidonic acid 10 μg∕animal then given alloxan injection, and arachidonic acid group received it, until offspring age of three weeks. Six male offspring from each group were included in this study at ages of newborn, three-week-old, two-month-old, and their body measurements were recorded. Lumbar vertebrae and pancreas specimens were examined by light microscopy, morphometry, transmission electron microscopy (TEM), and immunohistochemistry for insulin expression.
RESULTS
In alloxan-induced diabetes newborn, three-week-old, and two-month-old rats, body measurements were significantly declined, histomorphometry of 6th lumbar vertebrae revealed disorganized chondrocytes, with vacuolated cytoplasm, empty lacunae, diminished matrix staining, with areas devoid of cells. TEM showed shrunken reserve and proliferative cells, with irregular nuclei, and damaged mitochondria. In contrast, alloxan + arachidonic acid group had cytoarchitecture of lumbar vertebrae that were like control group. Histomorphometry of pancreas in alloxan-induced diabetes group showed significant reduction in pancreatic islets number and surface area, damaged pancreatic islet cells appeared atrophied with apoptotic nuclei, and very weak insulin immunostaining. Whereas alloxan + arachidonic acid group displayed healthy features of pancreatic islets, which resembled control group, with strong insulin immunostaining.
CONCLUSIONS
Arachidonic acid mitigated alloxan-induced diabetes by its antidiabetic activity.
Topics: Alloxan; Animals; Arachidonic Acid; Blood Glucose; Diabetes Mellitus, Experimental; Female; Insulin; Islets of Langerhans; Lumbar Vertebrae; Male; Pregnancy; Rats
PubMed: 36074671
DOI: 10.47162/RJME.63.1.08 -
Lipids in Health and Disease Aug 2022Syntaxin regulates pancreatic β cell mass and participates in insulin secretion by regulating insulin exocytosis. In addition, syntaxin 4 reduces IFNγ and TNF-α...
Syntaxin regulates pancreatic β cell mass and participates in insulin secretion by regulating insulin exocytosis. In addition, syntaxin 4 reduces IFNγ and TNF-α signaling via NF-ĸB in islet β-cells that facilitates plasma glucose sensing and appropriate insulin secretion. Arachidonic acid (AA) has potent anti-inflammatory actions and prevents the cytotoxic actions of alloxan and streptozotocin (STZ) against pancreatic β cells and thus, prevents the development of type 1 diabetes mellitus (induced by alloxan and STZ) and by virtue of its anti-inflammatory actions protects against the development of type 2 diabetes mellitus (DM) induced by STZ in experimental animals that are models of type 1 and type 2 DM in humans. AA has been shown to interact with syntaxin and thus, potentiate exocytosis. AA enhances cell membrane fluidity, increases the expression of GLUT and insulin receptors, and brings about its anti-inflammatory actions at least in part by enhancing the formation of its metabolite lipoxin A4 (LXA4). Prostaglandin E2 (PGE2), the pro-inflammatory metabolite of AA, activates ventromedial hypothalamus (VMH) neurons of the hypothalamus and inhibits insulin secretion leading to reduced glucose tolerance and decreases insulin sensitivity in the skeletal muscle and liver. This adverse action of PGE2 on insulin release and action can be attributed to its (PGE2) pro-inflammatory action and inhibitory action on vagal tone (vagus nerve and its principal neurotransmitter acetylcholine has potent anti-inflammatory actions). High fat diet fed animals have hypothalamic inflammation due to chronic elevation of PGE2. Patients with type 2 DM show low plasma concentrations of AA and LXA4 and elevated levels of PGE2. Administration of AA enhances LXA4 formation without altering or reducing PGE2 levels and thus, tilts the balance more towards anti-inflammatory events. These results suggest that administration of AA is useful in the prevention and management of DM by enhancing the action of syntaxin, increasing cell membrane fluidity, and reducing VMH inflammation. Docosahexaenoic acid (DHA) has actions like AA: it increases cell membrane fluidity; has anti-inflammatory actions by enhancing the formation of its anti-inflammatory metabolites resolvins, protectins and maresins; interacts with syntaxin and enhance exocytosis in general and of insulin. But the DHA content of cell membrane is lower compared to AA and its content in brain is significant. Hence, it is likely DHA is important in neurotransmitters secretion and regulating hypothalamic inflammation. It is likely that a combination of AA and DHA can prevent DM.
Topics: Alloxan; Animals; Anti-Inflammatory Agents; Arachidonic Acid; Diabetes Mellitus, Type 2; Dinoprostone; Docosahexaenoic Acids; Humans; Inflammation; Insulins; Qa-SNARE Proteins; Streptozocin
PubMed: 35982452
DOI: 10.1186/s12944-022-01681-3 -
Oxidative Medicine and Cellular... 2022Plants are a significant source for the development of new phytomedicines due to their great clinical benefits, efficiency, cost-effectiveness, fewer side effects, and...
Plants are a significant source for the development of new phytomedicines due to their great clinical benefits, efficiency, cost-effectiveness, fewer side effects, and more affordable therapies. Numerous plants used in traditional treatments, such as Scop., have been effective in the treatment of diabetes mellitus (DM). Therefore, the study is aimed at assessing the phytochemical, antioxidant, and antidiabetic properties of . The hypoglycemic and hypolipidemic activity was evaluated in Swiss male Albino mice by administering an oral dose of 150-250 mg/kg of extracts in alloxan-induced diabetic mice for 15 days. The antioxidant activity and phytochemical composition of the extracts were assessed by using , diphenyl--picrylhydrazyl (DPPH) and hydrogen peroxide scavenging assays and through standard chemical procedures. The effects of extracts on blood glucose, body weight, lipid profile, and biochemical parameters like total cholesterol (TC), triglyceride (TG), low-density lipids (LDL), high-density lipids (HDL), plasma insulin, liver glycogen, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), urea, and creatinine were determined according to standard procedures. The activities of antioxidant enzymes such as superoxide-dismutase (SOD), peroxidase (POD), and catalase (CAT) were also analyzed spectrophotometrically. The hypoglycemic and hypolipidemic effects with chloroform extracts of 250 mg/kg were found significant in the treatment of diabetes in alloxanised mice compared to the diabetic group. The haematological parameters such as TC, TG, HDL, LDL, creatinine, urea, AST, ALT, and ALP were significantly improved ( < 0.01) by the chloroform extract of 250 mg/kg compared to the diabetic group. Treatment for 15 days showed significant elevation ( < 0.01) of antioxidant enzymes. Fourier-transform infrared spectroscopic (FTIR) and gas chromatography-mass spectrometry (GC-MS), column chromatography (CC), and nuclear magnetic resonance (NMR) analyses tentatively identified different phytoconstitutents and metabolites in leaves, which have been reported to possess antihyperglycemic properties. In conclusion, the chloroform extract of 250 mg/kg of possesses significant hypoglycemic and hypolipidemic potential which may prove the claimed use of the plant in amelioration of diabetes and associated complications in folkloric medicine. Additional studies are required for the purification, characterization, and structural elucidation of bioactive compounds.
Topics: Mice; Animals; Antioxidants; Alloxan; Diabetes Mellitus, Experimental; Chloroform; Creatinine; Plant Extracts; Hypolipidemic Agents; Hypoglycemic Agents; Triglycerides; Blood Glucose; Anacardiaceae; Liver
PubMed: 36624877
DOI: 10.1155/2022/8802178 -
PloS One 2022The micro- and macro-complications in diabetes mellitus (DM) mainly arise from the damage induced by Amadori and advanced glycation end products, as well as the released...
The micro- and macro-complications in diabetes mellitus (DM) mainly arise from the damage induced by Amadori and advanced glycation end products, as well as the released free radicals. The primary goal of DM treatment is to reduce the risk of micro- and macro-complications. In this study, we looked at the efficacy of aminoguanidine (AG) to prevent the production of early glycation products in alloxan-diabetic rabbits. Type1 DM was induced in rabbits by a single intravenous injection of alloxan (90 mg/kg body weight). Another group of rabbits was pre-treated with AG (100 mg/kg body weight) prior to alloxan injection; this was followed by weekly treatment with 100 mg/kg of AG for eight weeks. Glucose, insulin, and early glycation products (HbA1C and fructosamine) were measured in control, diabetic and AG treated diabetic rabbits. The effects of hyperglycemia on superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx), reduced glutathione (rGSH), nitric oxide, lipid peroxides, and protein carbonyl were investigated. Alloxan-diabetic rabbits had lower levels of SOD, CAT, Gpx, and rGSH than control rabbits. Nitric oxide levels were considerably greater. AG administration restored the activities of SOD, CAT, Gpx enzymes up to 70-80% and ameliorated the nitric oxide production. HbA1c and fructosamine levels were considerably lower in AG-treated diabetic rabbits. The observed control of hyperglycemia and amadori adducts in alloxan-diabetic rabbits by AG may be attributed to decrease of stress and restoration of antioxidant defenses.
Topics: Alloxan; Animals; Antioxidants; Case-Control Studies; Catalase; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Drug Administration Schedule; Gene Expression Regulation; Glutathione; Glutathione Peroxidase; Guanidines; Hyperglycemia; Lipid Peroxidation; Nitric Oxide; Oxidative Stress; Rabbits; Superoxide Dismutase
PubMed: 34986201
DOI: 10.1371/journal.pone.0262233 -
Molecules (Basel, Switzerland) May 2021Diabetic dyslipidemia and hyperglycemia contribute to excessive reactive oxygen species (ROS) production, leading to deleterious complications, such as nephropathy,...
Diabetic dyslipidemia and hyperglycemia contribute to excessive reactive oxygen species (ROS) production, leading to deleterious complications, such as nephropathy, atherosclerosis and cardiac dysfunction, and target major organs in the body. The aim of this study was to investigate the effect of caffeic acid (CA) on mouse weight and survival, serum level of fasting blood glucose (FBG), serum lipid parameters and atherogenic indices, oxidative damage in blood, liver and kidney tissue, pathophysiological changes and their function markers in healthy and alloxan-induced type 1 diabetic mice. Diabetes was induced in mice with a single intravenous injection of alloxan (75 mg kg). Two days later, CA (50 mg kg) was given intraperitoneally for seven days in diabetic mice. Diabetes affected glucose level, lipid profile, hematological and biochemical parameters, induced DNA damage and apoptotic/necrotic death in whole blood cells, liver and kidney, leading to weight loss and a decreased lifespan. CA treatment of diabetic mice revealed a protective effect on the liver and kidney, hypoglycemic and hypolipidemic properties and high protection against atherogenic outcomes. The obtained results suggest that CA is a safe and potent agent against diabetes that acts as an effective antioxidant in reducing serum glucose, lipid profile and atherogenic indices, leading to increased lifespan in mice.
Topics: Alloxan; Animals; Antioxidants; Apoptosis; Atherosclerosis; Blood Glucose; Caffeic Acids; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Erythrocytes; Hemolysis; Hyperglycemia; Hypoglycemia; Lipid Peroxidation; Lipids; Liver; Male; Mice; Necrosis; Oxidative Stress; Reactive Oxygen Species; Risk Assessment
PubMed: 34071554
DOI: 10.3390/molecules26113262