Pdf antidiabetic properties and mechanism of action of. Insulin deficiency in turn leads to chronic hyperglycemia with disturbances of carbohydrates, fat and protein metabolism. Studies have suggested that stz is preferably absorbed by insulinsecreting. The mechanism of alloxan and streptozotocin action in b. Again, this insulinopenia syndrome, called streptozotocin diabetes, is caused by the specific necrosis of the pancreatic beta cells and streptozotocin has been the agent of choice for the induction of diabetes mellitus in animals ever since 3, 16. This study investigated the beneficial effects and mechanism of action of the juice of momordica charantia in streptozotocin stzinduced diabetes mellitus in rats. The mechanism of alloxan and streptozotocin action in b cells of the rat pancreas. Key words alloxan streptozotocin pancreatic b cells mechanism of action diabetes the induction of experimental diabetes in.
Papich dvm, ms, dacvcp, in saunders handbook of veterinary drugs fourth edition, 2016. Because pancreatic beta cells have high concentrations of glucose transporter 2 glut2, streptozocin is selectively toxic to these cells. It is a cytotoxic methyl nitrosourea moiety nmethylnnitrosourea attached to the glucose 2deoxyglucose molecule. Antidiabetic properties and mechanism of action of orthosiphon stamineus benth bioactive subfraction in streptozotocininduced diabetic rats. Streptozotocin, an antibiotic derived from streptomyces achromogenes, has a direct cytotoxic effect on pancreatic islet. The mechanisms of alloxan and streptozotocininduced. In the long run, streptozotocin may be of great importance not only in understanding the mecha nisms of diabetogenesis and oncogenesis but also as an antitumour agent for which the food and drug. Standard operating procedure for streptozotocin stz in. Group 2 was given streptozotocin and treated with saline for 2 wk streptozotocin group. Thus, it can be concluded that the pancreatic beta cell toxicity and the resultant diabetogenicity of alloxan are due to redox cycling and the generation of toxic ros. The chemical properties of stz are presented as follows. Streptozotocin induces rapid degradation of deoxyribonucleic acid dna in actively dividing or resting bacillus subtilis cells. Its activity appears to occur as a result of formation of methylcarbonium ions, which alkylate or bind with many intracellular.
The objective of the present study was to investigate the mechanism of action for the antidiabetic activity of aqueous leaf extract of c. Introduction diabetes mellitus is a metabolic disorder resulting from a defect in insulin secretion, insulin action or both. Group 3 was given the vehicle for streptozotocin and saline for 1 wk, then received manganese for 2 wk salinemanganese group. Streptozotocin je organsko jedinjenje, koje sadrzi 8 atoma ugljenika i ima molekulsku masu od 265,221 da. Pdf the mechanism of alloxan and streptozotocin action. The most usual substances to induce diabetes in the rat are alloxan and streptozotocin.
Streptozotocin definition of streptozotocin by medical. You may need frequent blood tests to make sure streptozocin is not causing harmful effects. Preparation, administration, handling and care of streptozotocin stz revision no. Characterisation of streptozotocin induced diabetes. Streptozocin also known as streptozotocin is an agent with specific effects on pancreatic beta cells. The catalog displays all strengths and sizes along with the description, imprint code, ndc and photo for each product. The jnk3 inhibitor xii, sr3576, also referenced under cas 1164153223, controls the biological activity of jnk3. Elucidation of molecular mechanisms of streptozotocin. Pdf on the mechanisms of diabetogenic effects of alloxan. Mechanism streptozotocin is a glucosamine nitrosourea compound. However, after several years of research, the mechanism of action of stz that results in cell death has been elucidated. Antidiabetic properties and mechanism of action of gynura procumbens water extract in streptozotocininduced diabetic rats zurina hassan 1, mun fei yam 1,2, mariam ahmad 1 and ahmad pauzi m. Only select registry of toxic effects of chemical substances rtecs data is presented here. Merr family compositae is cultivated in southeast asia, especially indonesia, malaysia and thailand, for medicinal purposes.
As with other alkylating agents in the nitrosourea class, it is toxic to cells by causing damage to the dna, though other mechanisms may also contribute. Yusof 3 1 school of pharmaceutical sciences, universiti sains malaysia, 11800 minden, penang, malaysia. Diabetic complications consortium diacomp protocols edited by ram 121415 1 of 3 pages lowdose streptozotocin induction protocol mouse. Characterisation of streptozotocin induced diabetes mellitus in swiss albino mice 11sachin arora, shreesh kumar ojha and divya vohora2 2department of pharmacology, faculty of pharmacy, jamia hamdard, new delhi, india abstract. Streptozotocin is a pancreatic betacellspecific cytotoxin and is widely used to induce experimental type 1 diabetes in rodent models. Difference spectroscopy showed that the antibiotic interacts specifically with cytosine containing mononucleotides in vitro. An antibiotic, c 8 h 15 n 3 o 7, produced by an actinomycete streptomyces achromogenes, used primarily to treat pancreatic tumors affecting the islets of langerhans. While receiving streptozocin, you should be able to get to a hospital or emergency room quickly in case you have a serious side effect. Streptozotocin use in mice and rats version 1 date of publication. Thus we hypothesized that exogenous leptin administered to mice with streptozotocin stzinduced diabetes reverses hyperglycemia through direct action on. Streptozotocin stz is commonly used to induce experimental diabetes in animals. Both effects can be attributed to its specific chemical properties, namely its alkylating potency see text box.
Streptozocin can harm your liver or kidneys, and may also cause severe vomiting or diarrhea. The general consensus was to acceptthe view that streptozotocin is a particularly appropriate experimen tal tool for studying the pathology of natural diabetes in the human rasch and in this respect several injec. Mode of action of streptozotocin pubmed central pmc. Coh29 is an orally available, aromatically substituted thiazole and inhibitor of the human ribonucleotide reductase rnr, with potential antineoplastic activity. Yet the mechanism of leptinmediated reversal of hyperglycemia has not been fully defined. In some cases, health care professionals may use the trade name zanosar when referring to the generic drug name streptozocin. A single intravenous streptozotocin injection 75 mgkg into fasted animals causes a decrease in insulin levels, hyperglycemia, an increase in serum free fatty acids, and an elevation in hepatic glucose6phosphatase activity. To better understand the insulinindependent plasma glucoselowering action of metformin, we used streptozotocin stzinduced diabetic rats to investigate the possible mechanisms. As a result of the streptozotocin action, b cells undergo the destruction by necrosis. The product catalog provides you with a full listing of tevas brand and generic product lines. Animal models to test drugs with potential antidiabetic activity. Concurrently, in a series of animal models, normal, streptozotocin stz diabetic and sand rats were used in the inverted sac model to determine the mechanism.
Streptozotocin does not cross the bloodbrain barrier, but its metabolites are found in cerebral spinal fluid. Health hazards streptozotocin is an antibiotic that is produced by stretomyces achromogenes, it is a toxic and carcinogenic material. This study evaluated the in vivo hypoglycemic properties of the water extract of g. Antidiabetic properties and mechanism of action of gynura. Because the end result of alloxan and streptozotocin treatment is qualitatively similar, the present study was undertaken to determine whether the two agents had a common mechanism of diabetogenic action at the biochemical level. The present study was designed to investigate the characteristics of diabetes mellitus induced by. The liver is a key organ regulating glucose metabolism and is also a target of leptin action. Although their cytotoxicity is achieved via different pathways, their mechanisms of beta cell selective action are identical. The objective of this study is to induce experimental diabetes mellitus by streptozotocin in normal adult wistar rats via comparison of changes in body weight, consumption of food and water, volume of urine and levels of glucose, insulin and. Streptozotocin is an antimicrobial agent and has also been used as a chemotherapeutic alkylating agent. Diabetes mellitus was associated with significant p p m.
The precise molecular mechanism of stz cytotoxicity is however not clear. Elucidation of mechanism of action of cassia auriculata. Alloxan and streptozotocin are the most prominent diabetogenic chemicals in diabetes research. Streptozotocin diabetes is caused by the specific necrosis of the pancreatic. Get a printable copy pdf file of the complete article 1. On the mechanisms of diabetogenic effects of alloxan and streptozotocin article pdf available in diabetologie metabolismus endokrinologie vyziva 143. Feeney, in the laboratory rabbit, guinea pig, hamster, and other rodents, 2012. The mechanism of their action in b cells of the pancreas has been intensively investigated and now is quite well understood. Holarrhena antidysenterica had, diabetes, streptozotocin, hypoglycemia. A single intravenous streptozotocin injection 75 mgkg into fasted animals causes a decrease in insulin levels, hyperglycemia, an. The cytotoxic action of both these diabetogenic agents is mediated by reactive oxygen species, however, the source of their generation is. Comparison of the chemical properties of alloxan and streptozotocin. Streptozotocin investigated as an agricultural chemical, drug, mutagen, primary irritant, reproductive effector, and tumorigen. Although its mechanism of action is not completely clear, streptozocin is known to inhibit dna synthesis, interfere with biochemical reactions of nad and nadh, and inhibit some enzymes involved in gluconeogenesis.
Alloxan streptozotocin pancreatic b cells mechanism of action diabetes the induction of experimental diabetes in the rat using chemicals which selectively destroy pancreatic b cells is very convenient and simple to use. Oral intake of metformin decreased the plasma glucose of stzinduced diabetic rats with a parallel increase of plasma. Streptozotocin induces rapid degradation of deoxyribonucleic acid. Glucose absorption from the intestines and its glucose uptake in abdominal skeletal. Streptozotocin definition of streptozotocin by the free. An antibiotic, c8h15n3o7, produced by an actinomycete, used primarily to treat pancreatic tumors affecting the islets of langerhans. Hypoglycemic effect of holarrhena antidysentericaseeds on. Standard operating procedure for streptozotocin stz in animals 1. The mechanisms of alloxan and streptozotocininduced diabetes. Group 4 was injected with streptozotocin and later treated in the same way as in group 3 streptozotocinmanganese group. Another possible mechanism of the diabetogenic action of streptozotocin that results in cell death has been attributed to its ability to act as nitric oxide donor in pancreatic cells which inhibits aconitase activity, leading to dna alkylation and damage.