Streptozotocin - Health Article

Streptozotocin

What is streptozotocin?


Streptozotocin (STZ) is an entity belonging to the classes of substances Glucosamine and the nitrosoureas and naturally occurring chemical compound that is specifically toxic to the insulin-producing beta cells in the islets of Langerhans of the pancreas. It is used therapeutically as a cytostatic agent in the treatment of tumors known as insulinoma beta cells. In experimental medicine, it is used in diabetes research for triggering of diabetes mellitus in animals.

Features and Effects


Streptozotocin is a white to pale yellow powder. With regard to its chemical structure, it contains methylnitrosourea bound to the C2 position of glucose. It thus belongs to the substance class of nitrosoureas and acts like some other similar substances alkylating. That is, it effects an incorporation of the alkyl groups in the DNA, whereby the cell division is inhibited. DNA damage by the generation of free radicals is also discussed as a mechanism of action. Streptozocin so is mutagenic (mutagenic) and carcinogenic. 
The selective effect on the beta cells due to the fact that because of the glucose is transported streptozocin structure through the glucose transporter GLUT2, which occurs in high density in the membrane of the beta cells, in the cell. In the cell, a cleavage between the glucose content and the methylnitrosourea, which is responsible for the DNA-damaging effects occurs.

Application


The therapeutic application of streptozotocin is limited due to the risks involved in the treatment of insulinomas, which can not be surgically removed. In affected patients, the tumor size and thus associated with the excessive insulin production of tumor symptoms such as the repeated occurrence of hypoglycaemia may be reduced by the treatment. The application is by intravenous injection over several days, with a need for appropriate recurrence after four to six weeks.

Within experimental application for the induction of diabetes mellitus in experimental animals, streptozocin has prevailed largely to substances previously used as alloxan or steroids. Its use is, however, also decreased by the availability of various animal models in spontaneously, such as the BB-rat or NOD mouse. Depending on the question to be examined can also be triggered as a similar to human type 1 diabetes autoimmune process by repeated administration of subacute doses by single administration of an appropriate dose, an acute insulin-dependent diabetes. By treatment of animals immediately after the birth, the induction of a non-insulin-dependent diabetes mellitus is possible.

Historical Information


Streptozotocin was found in 1956 as some antibiotic substance by scientists at the Upjohn Company in a strain of the soil bacterium Streptomyces achromogenes. A patent was applied for and granted in 1959 in March 1962. Mid-1960s, the selective toxicity against the beta cells in the islets of Langerhans of the pancreas was discovered. This led shortly thereafter for use in experimental diabetes research, diabetes mellitus to elicit targeted in experimental animals.

At the same time, initial studies to clinical application for the treatment of insulin-producing pancreatic tumors began. Further studies at the National Cancer Institute led 1982 licensed as a drug by the US Drug Administration Food and Drug Administration (FDA). The Upjohn Company, in the context of several acquisitions later came into the possession of the company Pfizer, streptozocin marketed under the trade name Zanosar®. Since the expiry of patent protection is available as a generic.

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