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diabetes treatment, what are stz and alloxan

by Caden Metz Published 3 years ago Updated 2 years ago
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Alloxan (ALX) and streptozotocin (STZ) bind to the glucose transporter- (GLUT-) 2 receptor, causing cell death by reactive oxygen species (ROS) generation (ALX) or inducing DNA damage (STZ) directly. These diabetogenic agents, however, may have different toxicological effects depending on the dose and route of administration.

Alloxan and streptozotocin are the most popular diabetogenic agents used for assessing the antidiabetic or hypoglycemic capacity of test compounds. Notably, alloxan is far less expensive and more readily available than streptozotocin.

Full Answer

Is streptozotocin or alloxan better for Type 1 diabetes?

Alloxan and streptozotocin are toxic glucose analogues that preferentially accumulate in pancreatic beta cells via the GLUT2 glucose transporter. In the presence of intracellular thiols, especially glutathione, alloxan generates reactive oxygen species (ROS) in a cyclic redox reaction with its reduction product, dialuric acid.

Can ALX be replaced by STZ for induction of diabetes in laboratory animals?

Experimental diabetes induced by alloxan and streptozotocin: The current state of the art ... chemical methods of alloxan- and streptozotocin-induced diabetes represent the most important and highly preferable experimental models for this pathological condition. Therefore, the aim of this article was to review the current knowledge related to ...

What is the best model for STZ-induced diabetes?

Sep 01, 1991 · Streptozocin (STZ) and alloxan (ALX) exhibit the most potent diabetogenicity and are used for induction of experimental diabetes mellitus. An understanding of the mechanisms of action of the typical diabetogenic agents is important for elucidating the causes of diabetes. ... These findings may support Okamoto's proposal that STZ and ALX induce ...

Is streptozotocin (STZ) diabetic?

Mar 21, 2022 · Alloxan (ALX) and streptozotocin (STZ) bind to the glucose transporter- (GLUT-) 2 receptor, causing cell death by reactive oxygen species (ROS) generation (ALX) or inducing DNA damage (STZ) directly . These diabetogenic agents, however, may have different toxicological effects depending on the dose and route of administration . Although they have …

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T2D in these rats was induced by an intraperitoneal injection of Streptozotocin (65 mg/kg) and Nicotinamide (110 mg/kg) (15 min between the two injections). Treatment lasted for …

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What is the difference between alloxan and streptozotocin?

As a thiol reagent, alloxan also selectively inhibits glucose-induced insulin secretion through its ability to inhibit the beta cell glucose sensor glucokinase. Following its uptake into the beta cells, streptozotocin is split into its glucose and methylnitrosourea moiety.

What is alloxan treatment?

Alloxan is a toxic chemical. It has been used to induce diabetes in experimental animals by destroying the insulin-secreting cells of Langerhans islet in pancreas. It provides protection against some of the damage induced by free radicals. It may neutralize free radicals.

What does alloxan do to the body?

Alloxan is a toxic glucose analogue, which selectively destroys insulin-producing cells in the pancreas (that is, beta cells) when administered to rodents and many other animal species.

What food contains alloxan?

Alloxan is a by-product of the flour-bleaching process that makes flour “white.” You can make a choice to buy unbleached or whole wheat flour, instead of white flour that might be contaminated.Mar 6, 2015

Does Maida contain alloxan?

A common misconception is that maida contains alloxan, which itself is banned in a lot of countries for usage in food, added as a bleaching agent or formed as a byproduct of bleaching. While it is a minor product of xanthophyll oxidation, there is no evidence that trace amounts of alloxan formed comprise a health risk.

Where is streptozotocin found?

Streptozotocin (STZ) is a naturally occurring chemical derived from Streptomyces achromogenes that is particularly toxic to the insulin-producing beta cells of the pancreas in mammals.

How does STZ cause diabetes?

Diabetes is induced by streptozotocin (STZ), a glucosamine–nitrosourea compound derived from Streptomyces achromogenes that is used clinically as a chemotherapeutic agent in the treatment of pancreatic β cell carcinoma. STZ damages pancreatic β cells, resulting in hypoinsulinemia and hyperglycemia.

How does alloxan induce diabetes in rodents?

edulis in alloxan induced diabetic rats. Alloxan induces diabetes through ROS that leads to a rapid destruction of pancreatic beta cells causing hyperglycemia (Stanely et al., 2000). Hyperglycemia in turn increases the generation of free radicals by glucose auto-oxidation (Bajaj and Khan, 2012).Sep 27, 2018

What is glycosylated hemoglobin?

A glycated hemoglobin test measures the amount of glucose (sugar) in your blood. The test is often called A1c, or sometimes HbA1c. It's a simple blood test used to: Detect prediabetes — high sugar levels that can lead to diabetes, heart disease and stroke.Mar 30, 2021

Does alloxan cause diabetes in humans?

Alloxan causes diabetes by a mechanism which basically involves partial degradation of the beta (β) cells of pancreatic islets and subsequent compromise in the quality and quantity of insulin produced by these cells.

What is diabetes mellitus?

Abstract. Diabetes mellitus is a chronic metabolic disorder with a high prevalence worldwide. Animal models of diabetes represent an important tool in diabetes investigation that helps us to avoid unnecessary and ethically challenging studies in human subjects, as well as to obtain a comprehensive scientific viewpoint of this disease. ...

Is diabetes mellitus a chronic disease?

Diabetes mellitus is a chronic metabolic disorder with a high prevalence worldwide. Animal models of diabetes represent an important tool in diabetes investigation that helps us to avoid unnecessary and ethically challenging studies in human subjects, as well as to obtain a comprehensive scientific viewpoint of this disease. Although there are several methods through which diabetes can be induced, chemical methods of alloxan- and streptozotocin-induced diabetes represent the most important and highly preferable experimental models for this pathological condition. Therefore, the aim of this article was to review the current knowledge related to quoted models of diabetes, including to this point available information about mechanism of action, particular time- and dose-dependent protocols, frequent problems, as well as major limitations linked to laboratory application of alloxan and sterptozotocin in inducing diabetes. Given that diabetes is known to be closely associated with serious health consequences it is of fundamental importance that current animal models for induction of diabetes should be continuously upgraded in order to improve overall prevention, diagnosis and treatment of this pathological condition.

Does streptozotocin affect calcium levels?

Also, streptozotocin treatment induced a reduction in intracellular calcium levels and inhibited capsaicin induced calcium transients and membrane depolarization. Alloxan did not affect calcium levels or membrane potential in primary nociceptive neurons.

What is DN in a diabetic?

Diabetic neuropathy (DN) commonly occurs in diabetics, affecting approximately 50% of both type 1 and 2 diabetic patients. It is a leading cause of non-traumatic amputations. Oxidative stress could play a key role in the pathophysiology of DN. This study aimed to investigate the potential neuroprotective effect of carvedilol on STZ-induced DN in rats. Thirty male Sprague Dawley rats (weighing 200–250 g) were randomly divided into five groups (six/group), where group 1 (negative control) received only the vehicle (0.5% of carboxymethyl cellulose orally 1 ml/kg). DN was induced by a single injection of remaining rats with streptozotocin (STZ; 50 mg/kg, i.p.). After diabetes induction, group 2 served as the diabetic untreated animals; while groups 3 and 4 were treated with carvedilol (1 and 10 mg/kg/d, orally, respectively). Group 5 received a-lipoic acid as a reference neuroprotective (100 mg/kg/d, orally). All treatments were continued for 45 days after diabetes induction, followed by behavioural tests. After sacrificing the animals, dorsal root ganglia, and sciatic nerves were collected for histopathological examination and biochemical assessments. Briefly, STZ administration caused cold allodynia, induced oxidative stress, and increased nerve growth factor (NGF) concentration. Nevertheless, carvedilol improved the behavioural tests, ameliorated the oxidative imbalance as manifested by reducing malondialdehyde, restoring glutathione content, and superoxide dismutase activity. Carvedilol also decreased NGF concentration in DRG homogenate. In conclusion, this study demonstrates the neuroprotective effect of carvedilol in an experimentally induced DN rat model through–at least partly–its antioxidant effect and reduced NGF concentration in DRG.

How much streptozotocin is in a rat?

Streptozotocin (17.5 and 35 mg/kg), alloxan (15 and 30 mg/kg) or vehicle were injected in adult male rats and the animal groups were separated according to glycemic levels. Body mass, glycemia and paw mechanical sensitivity were evaluated for 5 weeks.

Is streptozotocin toxic to animals?

There are advantages that explain why streptozotocin is the first choice for animal diabetes models. Alloxan is an unstable molecule and more toxic to some non-target tissues, such as the kidneys (Lenzen, 2008; Radenković et al., 2016).

What is diabetes mellitus?

Diabetes Mellitus is known as a syndrome, a collection of disorders with high blood glucose level & glucose intolerance as its feature, either because of insulin deficiency or insulin impairment or both . Diabetes Mellitus, based on insulin, is broadly classified into two types. Type one indicates the distraction of pancreatic β - cells that leads to diabetes mellitus, in which insulin is necessary to prevent ketoacidosis, coma, death. Type two diabetes is characterized by disorders of insulin resistance & secretion. Male Wistar albino rats with an average weight of 180-250 g were used in this study. With a 12 hours’ light and dark period, they were kept under normal conditions (room temperature 24-27oC and humidity 60-65 %). The free access of drinking water & pellet diet to male Wistar albino rats was allowed, as per the CPCSEA guidelines. Anti-diabetic activity of Compound 2- (4- [ (2-hydroxyacetyl benzyl) ketoamino]-phenyl amino-methyl)- hydrobenzophenon, male Wistar albino rats were divided into four different groups. 1ml of blood samples were collected directly into anticoagulant bottles from the tail vein & later plasma was collected after centrifugation. Blood sugar levels were determined by spectrophotometer. There was a significant decrease in blood sugar levels in Alloxan + Glibenclamide and Alloxan + Compound groups on compared to control. The present self-funded study concludes that antidiabetic activity of 2- (4- [ (2-hydroxyacetyl benzyl) ketoamino]-phenyl amino-methyl)- hydrobenzophenon in Alloxan induced diabetic rats significantly shows decreed blood sugar levels when compared to the control group.

What is Ajuga Integrifolia used for?

Traditional healers and the community have used the roots of Ajuga integrifolia for the treatment of diabetes mellitus. It is not scientifically validated for its antidiabetic activity previously. Therefore, the objective of the present study was to determine the hypoglycemic and antidiabetic activity of Ajuga integrifolia. Ajuga integrifolia roots’ crude extract and solvent fractions were prepared. The doses of 100 mg/kg, 200 mg/kg, and 400 mg/kg of crude root extract and solvent fractions were used on normoglycemic, oral glucose loaded, and streptozotocin-induced diabetic mice models to determine their hypoglycemic and antihyperglycemic activities. The crude extract and solvent fractions’ effect on bodyweight was also evaluated on streptozotocin-induced diabetic mice. A standard drug in all cases was glibenclamide (5 mg/kg), and the blood glucose level was measured by using a glucose meter. Data analysis was performed by using Statistical Package for Social Sciences version 21. One-way analysis of variance followed by Tukey’s post hoc multiple comparison test was used to analyze the data. p value

Is gestational diabetes mellitus a risk factor for pregnancy?

Gestational diabetes mellitus (GDM) characterized by hyperglycemia during pregnancy is a risk factor for various maternal and fetal complications. The key pathophysiological mechanisms underlying its development have not been elucidated, largely due to the lack of a model that accurately simulates the major clinical and pathological features of human GDM. In this review, we discuss the refined criteria for an ideal animal model of GDM, focusing on the key clinical and pathophysiological characteristics of human GDM. We provide a comprehensive overview of different models and currently used species for GDM research. In general, insulin insufficiency consequent to pancreatic β-cell death represents the current leading strategy to mimic human GDM-like hyperglycemia in animals. Nonetheless, these models have a limited capacity to mimic the natural history of GDM, the marked alteration in circulating estrogen/ progestogen, obesity and its related metabolic complications. We discuss emerging evidence of the increased susceptibility to GDM in rodents and large animals with genetic modifications in pregnancy-related hormones. An appraisal of current GDM models suggests that a combination strategy involving dietary stress, pregnancy-related hormones, insulin resistance and metabolic disorders might enable the development of better GDM models and expedite the translation of basic research findings to GDM treatment.

Can streptozotocin be used for diabetes?

Both alloxan and streptozotocin can be used for induction of type 1 and type 2 diabetes. Still, these chemicals are most commonly used for induction of type 1 diabetes because they are unable to directly induce an insulin resistance.

Is there a protocol for chemically induced diabetes?

Currently there are several protocols for chemically-induced diabetes that can be used for development of animal models regarding type 1, type 2, or gestational diabetes. Nonetheless, there is no standard protocol that has been unanimously accepted by the scientific community. The previous subject matter was created to bring together different protocols and to highlight the positive and negative aspects of each of them. Summary tables for the induction of type 1, type 2 and gestational diabetes ( Table 3) were created and they contain all the above mentioned properties of each model with given recommendations that were proposed based on evidences found in literature. Summary and recommendations will hopefully provide adequate information that could help scientific personnel to reduce number of animals needed for their investigations, to shorten the overall time of investigation, to increase the quality of their work and to preserve their finance resources.

What are the characteristics of type 1 diabetes?

The main characteristics of type 1 diabetes are high glucose and low insulin levels in blood. Type 2 diabetes mellitus (T2DM) is the most common form of diabetes, and it represents more than 90% of all cases ( Cefalu, 2006 ).

What is the 3Rs concept?

One of the most important regulation concepts of animal welfare is the 3Rs concept (replacement, reduction and refinement) created by Russell and Burch in 1959 ( Kroeger, 2006 ).

What is the name of the disease that causes an increase in blood glucose levels?

1. Introduction. Diabetes is a chronic metabolic disorder, which appears when there is a defect in insulin secretion or/and when the body cannot use insulin in an effective way. This leads to an increase in blood level of glucose, which is called hyperglycemia.

What is 5% dextrose solution?

Short- and long- term diabetes. 5% dextrose solution (on a first day) Investigation of kidney, liver and biliary excretion. Applicable in guinea pig and cat, can be (but not the best choice) used for investigation of chemicals with antioxidant effect, more chance to develop type 2 diabetes.

What is the most common type of diabetes?

Type 2 diabetes mellitus (T2DM) is the most common form of diabetes, and it represents more than 90% of all cases ( Cefalu, 2006 ). This type is known as a progressive disorder, and it is associated with gradual diminishing of pancreatic function over a period of time.

The Effect Of Alloxan, And Alloxan-induced Diabetes On The Kidney

The effect of alloxan, and alloxan-induced diabetes on the kidney. Alloxan is known to induce diabetic renal changes as well as causing nephrotoxic alterations. However, no ultrastructural study has been performed to differentiate diabetic verses toxic affects of alloxan to the tubule and/or glomerulus.

Alloxan - Wikipedia

Alloxan, sometimes referred to as alloxan hydrate, refers to the organic compound with the formula OC (N (H)CO)2C (OH)2. It is classified as a derivative of pyrimidine . The anhydrous derivative (OC (N (H)CO)2CO is also known as well as a dimeric derivative. These are some of the earliest known organic compounds.

Alloxan-induced Diabetes Causes Morphological And Ultrastructural Changes In Rat Liver That Resemble The Natural History Of Chronic Fatty Liver Disease In Humans

Copyright © 2015 Amanda Natália Lucchesi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Purpose.

Antidiabetic Activity Of Phyllanthus Amarus Schum And Thonn (euphorbiaceae) On Alloxan Induced Diabetes In Male Wistar Rats

Antidiabetic Activity of Phyllanthus amarus Schum and Thonn (Euphorbiaceae) on Alloxan Induced Diabetes in Male Wistar Rats Povi Lawson-Evi , Kwashie Eklu-Gadegbeku , Amegnona Agbonon , Kodjo Aklikokou , Edmond Creppy and Messanvi Gbeassor Abstract: This study was undertaken to investigate the antidiabetic effect of aqueous and hydroalcoholic extract of Phyllanthus amarus Schum and Thonn, a medicinal plant used in Togo for treatingdiabetes and many others diseases.

Alloxan: An Unpredictable Drug For Diabetes Induction?

Alloxan: An unpredictable drug for diabetes induction? Department of Pharmacology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India Correspondence to: Dr.

The Mechanisms Of Alloxan- And Streptozotocin-induced Diabetes

The mechanisms of alloxan- and streptozotocin-induced diabetes. Institute of Clinical Biochemistry, Hannover Medical School, 30623, Hannover, Germany. Diabetologia. 2008 Feb;51 (2):216-26. Epub 2007 Dec 18.

Alloxan-induced Diabetes Triggers The Development Of Periodontal Disease In Rats

Alloxan-Induced Diabetes Triggers the Development of Periodontal Disease in Rats Affiliation Department of Biological Sciences, School of Dentistry of Bauru, So Paulo University, Bauru, So Paulo, Brazil Affiliation Department of Biological Sciences, School of Dentistry of Bauru, So Paulo University, Bauru, So Paulo, Brazil Affiliation Department of Surgery and Orthopedics, School of Medicine of Botucatu, Sao Paulo State University, Botucatu, So Paulo, Brazil Affiliation Department of Biological Sciences, School of Dentistry of Bauru, So Paulo University, Bauru, So Paulo, Brazil Affiliation Department of Surgery and Orthopedics, School of Medicine of Botucatu, Sao Paulo State University, Botucatu, So Paulo, Brazil Affiliation Department of Stomatology, School of Dentistry of Bauru, So Paulo University, Bauru, So Paulo, Brazil Affiliation Department of Biological Sciences, School of Dentistry of Bauru, So Paulo University, Bauru, So Paulo, Brazil *To whom correspondence should be addressed.

What is STZ in animal models?

Streptozotocin (STZ)-Induced Diabetic Model. Creative Biolabs is one of the most reliable industry leaders professional in developing animal models of diseases. At Creative Biolabs, all studies in chemically-induced diabetic mice/rats models can be customized to meet your specific requirements.

Is a mouse a type 1 diabetic?

Secondly, the small size of mice makes it cost-effect ive to establish.

What is diabetes mellitus?

Diabetes mellitus is a metabolic disease characterized by hyperglycemia that is caused by a relative or complete insulin deficiency. Among several different forms of diabetes, the two most common are type 1 and type 2 diabetes.

What is the difference between type 1 and type 2 diabetes?

Type 1 diabetes is caused by the autoimmune destruction of pancreatic β-cells and a subsequent lack of insulin production, whilst type 2 diabetes is due to a combination of both insulin resistance and an inability of the β-cells to compensate adequately with increased insulin release.

What are the advantages of the mouse model?

Firstly, it closely resembles human type 1 diabetes with chronic pancreatic islet inflammation, insulitis, and insulin deficiency. Secondly, the small size of mice makes it cost-effective to establish.

What is Creative Biolabs?

Creative Biolabs provides various assessment options for testing the effectiveness of potential antidiabetic agents depending on your study objectives , including but not limited to: Additionally, Creative Biolabs also offers other types of rodent metabolic disease models that you may be interested in:

Does alloxan inhibit insulin secretion?

Alloxan has two distinct pathological effects: it selectively inhibits glucose-induced insulin secretion through specific inhibition of glucokinase, the glucose sensor of the beta cell, and it causes a state of insulin-dependent diabetes through its ability to induce ROS formation, resulting in the selective necrosis of beta cells. These two effects can be assigned to the specific chemical properties of alloxan, the common denominator being selective cellular uptake and accumulation of alloxan by the beta cell.

Is alloxan a cytotoxic substance?

Alloxan and streptozotocin are the most prominent diabetogenic chemicals in diabetes research. Both are cytotoxic glucose analog ues. Although their cytotoxicity is achieved via different pathways, their mechanisms of beta cell selective action are identical.

Does streptozotocin cause diabetes?

Streptozotocin (Fig. 2) inhibits insulin secretion and causes a state of insulin-dependent diabetes mellitus. Both effects can be attributed to its specific chemical properties, namely its alkylating potency (see text box: Comparison of the chemical properties of alloxan and streptozotocin). As with alloxan, its beta cell specificity is mainly the result of selective cellular uptake and accumulation.

Does streptozotocin affect glucose transport?

On the other hand, streptozotocin has no immediate, direct inhibitory effect upon glucose transport [ 77] or upon glucose phosphorylation by glucokinase [ 39 ]. However, at later stages of functional beta cell impairment, deficiencies in terms of gene expression and protein production lead to the deterioration of both glucose transport and metabolism [ 96 ].

Does streptozotocin affect insulin?

The effects of streptozotocin on glucose and insulin homeostasis reflect the toxin-induced abnormalities in beta cell function. Initially, insulin biosynthesis, glucose-induced insulin secretion and glucose metabolism (both glucose oxidation and oxygen consumption) are all affected [ 93 – 95 ].

Does streptozotocin cause insulin deficiency?

Conclusion. Both alloxan and streptozotocin induce insulin deficiency. While the mechanisms of beta cell-selective action through uptake via the GLUT2 glucose transporter and beta cell death via necrosis are identical, ROS in the case of alloxan and DNA alkylation in the case of streptozotocin mediate the toxic action of these glucose analogues ...

Is streptozotocin cytotoxic?

Introduction. Alloxan and streptozotocin are the most prominent diabet ogenic chemicals in diabetes research. Both are cytotoxic glucose analogues. Although their cytotoxicity is achieved via different pathways, their mechanisms of beta cell selective action are identical.

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