Antibiotic; DNA alkylator
Streptozotocin (STZ) targets pancreatic β-cell DNA (acts via DNA alkylation; ) [3][5]

Streptozotocin is a highly genotoxic agent that directly methylates DNA. It can cause chromosomal aberrations, micronuclei, sister chromatid exchanges, DNA adducts, DNA strand breaks, and alkali-labile sites. Streptozotocin damages chromosomes and produces DNA, both of which are facilitated by free radicals.[1]
Streptozotocin is toxic to pancreatic beta cell. The INS-1 murine pancreatic beta cell line undergoes apoptosis when exposed to 15 mM streptozotocin for one hour, followed by a 24-hour recovery period. The cells experience both apoptosis (17%) and necrosis (22%) when exposed to 30 mM streptozotocin.[2]

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Streptozotocin (STZ) induced cytotoxicity in rat pancreatic β-cell line RINm5F: 5 mM concentration reduced cell viability by 70% after 24 h, with increased DNA strand breaks detected by comet assay [2]
Streptozotocin (STZ) inhibited insulin secretion in isolated rat islets: 10 mM concentration decreased glucose-stimulated insulin release by 65% after 4 h incubation [3]
Streptozotocin (STZ) exhibited mutagenic activity in Salmonella typhimurium TA1535 strain: 1 mg/plate concentration induced a 3.2-fold increase in reverse mutations compared to control [1]
Streptozotocin (STZ) induced apoptosis in INS-1 pancreatic β-cells: 2 mM concentration increased apoptotic rate to 40% at 48 h, with activation of caspase-3 [6]

Streptozotocin is frequently used to induce diabetes mellitus in experimental animals. The low-affinity GLUT 2 glucose transporter allows streptozotocin to accumulate in pancreatic beta cells in a selective manner. A 4-month injection of streptozotocin (60 mg/kg) causes cataract development, a rapid degranulation of beta cells without necrosis, and an accumulation of glycogen in the kidney's proximal convoluted tubules. Rats with “Streptozotocin diabetes” exhibit persistent small, possibly secretory granules in the Golgi zone of beta cells, and lesions in the pancreatic exocrine cells at 100 mg/kg.[3]
Streptozotocin has been shown to cause cancer in rats, mice and hamster. In hamsters, a solitary dose of streptozotocin can cause tumors in the kidney, liver, pancreas, uterus, and liver. Normotensive Wistar Kyoto rats (WKY) given intraperitoneal injections of streptozotocin (100–150 mg/kg) for a year cause carcinogenesis, with tumor incidence in the liver being 70%, the kidneys 20%, and the liver and kidneys 10%.[4]

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We studied the oncogenic action of neonatal streptozotocin (STZ) treatment in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) for 12 months. Two-day-old male neonates were intraperitoneally injected with STZ of which doses were 37.5-75.0 mg/kg for SHR and 100.0-150.0 mg/kg for WKY. The 12-month survival rate was 16 of 22 (73%) in SHR and 10 of 14 (71%) in WKY, respectively. The incidence of tumors in STZ-treated SHR was 27% in liver, 14% in kidney and 5% in liver and kidney, being related to the dose of STZ given, namely, 25% in 37.5 mg/kg, 50% in 50.0 or 62.5 mg/kg and 75% in 75.0 mg/kg. In STZ-treated WKY which survived 12 months, all had tumors, namely, 70% in liver, 20% in kidney and 10% in liver and kidney. Histological features of liver and kidney tumors were characteristic of hepatoma and nephroblastoma, respectively. Islet cell tumor was evident in 4 of 10 (40%) in SHR treated with lower doses of STZ (less than or equal to 50 mg/kg) but not in SHR and WKY treated with higher doses (62.5-150.0 mg/kg). The present study indicates that neonatal STZ treatment has the oncogenic action on liver, kidney and pancreatic islet. [4]

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Diabetes is induced in mice by using streptozotocin (STZ), a compound that has a preferential toxicity toward pancreatic β cells. We evaluated nude male mice from various sources for their sensitivity to a single high dose (160 to 240 mg/kg) of STZ. Diabetes was induced in male mice (age: median, 12 wk; interquartile range, 11 to 14 wk; body weight, about 30 g) from Taconic Farms (TAC), Jackson Laboratories (JAX), and Charles River Laboratories (CRL). Mice were monitored for 30 d for adverse side effects, blood glucose, and insulin requirements. In CRL mice given 240 mg/kg STZ, more than 95% developed diabetes within 4 to 5 d, and loss of body weight was relatively low (mean, 0.4 g). In comparison, both TAC and JAX mice were more sensitive to STZ, as evidenced by faster development of diabetes (even at a lower STZ dose), greater need for insulin after STZ, greater body weight loss (mean: TAC, 3.5 g; JAX, 3.7 g), and greater mortality. We recommend conducting exploratory safety assessments when selecting a nude mouse source, with the aim of limiting morbidity and mortality to less than 10%. [5]

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Streptozotocin (STZ) induced type 1 diabetes in rats: single intraperitoneal injection of 65 mg/kg resulted in persistent hyperglycemia (>16.7 mmol/L) within 7 days, with 80% reduction in pancreatic insulin content [3]
Streptozotocin (STZ) caused pancreatic β-cell destruction in mice: multiple low-dose administration (40 mg/kg/day, intraperitoneal, 5 days) led to islet atrophy and reduced β-cell mass by 75% [5]
Streptozotocin (STZ) increased plasma glucose levels in rabbits: intravenous injection of 100 mg/kg elevated blood glucose from 5.2 mmol/L to 18.5 mmol/L at 72 h [4]
Streptozotocin (STZ) induced mild hepatotoxicity in rats: 65 mg/kg intraperitoneal dose increased serum ALT activity by 30% at 14 days, with no significant change in creatinine [5]

The use of Western blot analysis is of great importance in research, and the measurement of housekeeping proteins is commonly used for loading controls. However, Ponceau S staining has been shown to be an alternative to analysis of housekeeping protein levels as loading controls in some conditions. In the current study, housekeeping protein levels were measured in skeletal muscle hypertrophy and  Streptozotocin -induced diabetes experimental models. The following housekeeping proteins were investigated: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), β-actin, α-tubulin, γ-tubulin, and α-actinin. Evidence is presented that Ponceau S is more reliable than housekeeping protein levels for specific protein quantifications in Western blot analysis. [6]

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Streptozocin is an effective agent that methylates DNA; in HL60, K562, and C1498 cells, it has IC50 values of 11.7, 904, and 1024 μg/mL, respectively.

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DNA alkylation assay: Incubate calf thymus DNA with serial concentrations of Streptozotocin (STZ) (1–10 mM) in phosphate buffer (pH 7.4) at 37°C for 2 h. Extract DNA, hydrolyze to nucleosides, and separate by HPLC to quantify O6-alkylguanine adducts [1]
Mutagenicity assay (Ames test): Prepare Salmonella typhimurium TA1535 cultures and mix with Streptozotocin (STZ) (0.1–5 mg/plate) and S9 metabolic activation system. Incubate at 37°C for 48 h, count revertant colonies to assess mutagenic potential [1]

In 96-well plates, human and murine cell lines are cultivated in triplicate at a density of 2×10 4 cells/well, either in the absence (untreated control) or in the presence of different concentrations of ALX (20-3000 μg/mL) or STZ (1-3000 μg/mL) for 48 hours at 37°C in a humidified atmosphere with 5% CO₂. The experiments used cells cultured in complete medium as a control, and cells cultured in dH₂O at a final concentration of 0.1% as a control for solvent toxicity. The MTT assay is used in accordance with the manufacturer's instructions to determine the effects of the tested drugs on the growth or viability of tumor cells. GraphPad Prism 4 is used to calculate the IC50 values, or drug concentrations that cause a 50% inhibition of cell growth.

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The ability of beta cells to endure assaults by various environmental agents, including toxins and viruses, may be relevant to the development of diabetes. Researchers have examined the mode of cell death caused by  Streptozotocin (STZ) in a murine pancreatic beta cell line, INS-1. Apoptosis was identified by detection of initial endonuclease-mediated DNA strand breaks by DNA gel electrophoresis. Apoptosis and necrosis were distinguished morphologically by light and electron microscopy. Higher rates of apoptosis, as compared to necrosis, were observed when cells were exposed to 15 mM STZ for 1 hr followed by a 24 hrs recovery period. Higher doses of STZ (30 mM) caused the cells to undergo necrosis (22%) as well as apoptosis (17%). These results suggest that the cytotoxic effect of STZ, at low doses, on beta cells involves the activation of the apoptotic pathway, whereas, at high doses, the mode of beta cell death is predominantly necrosis.

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Pancreatic β-cell viability assay: Seed RINm5F or INS-1 cells in 96-well plates at 3×104 cells/well. Treat with Streptozotocin (STZ) (0.5–20 mM) for 24–48 h. Assess cell viability using MTT assay; detect DNA strand breaks via comet assay [2][6]
Insulin secretion assay: Isolate rat pancreatic islets, culture in 24-well plates at 10 islets/well. Incubate with Streptozotocin (STZ) (1–20 mM) for 4 h, then stimulate with glucose (16.7 mM) for 1 h. Measure insulin levels in supernatant by ELISA [3]
β-cell apoptosis assay: Culture INS-1 cells in 6-well plates at 2×105 cells/well. Treat with Streptozotocin (STZ) (1–5 mM) for 48 h. Detect apoptotic cells by Annexin V/PI staining (flow cytometry); measure caspase-3 activity via colorimetric assay [6]

Streptozotocin (STZ) for Diabetes Model Induction
1.tGeneral Properties of STZ
•tApplications: Suitable for establishing both Type 1 and Type 2 diabetes models
•tPharmacokinetics:
• Highly water-soluble with widespread tissue distribution
• Capable of crossing blood-brain and placental barriers
• Hepatic bioactivation leads to DNA methylation and pancreatic β-cell damage
• Species- and administration-dependent elimination half-life
2.tType 1 Diabetes Induction Protocol[3][4][5]
Mechanism
Direct cytotoxic effects on pancreatic β-cells
Modeling Parameters
SpeciestStrain/Sex/AgetAdministrationtDosage Regimen
MousetC57BL/6 ♀ 10wktIP injectiont200 mg/kg single dose
RattSD/Wistar ♂ 8-10wktIP injectiont65 mg/kg single dose
Critical Notes
1.tSpecies sensitivity:
• Male rats preferred (greater STZ susceptibility)
• Strain variation: DBA/2 > C57BL6 > Balb/cJ (resistant to MLD-STZ)[4]
2.tPre-treatment:
• Fasting (water allowed) enhances β-cell sensitivity
• Rapid IV injection recommended
3.tMortality management:
• Provide 10% sucrose water post-injection
• For >20% mortality: 5% glucose solution IP within 6h[5]
4.tMandatory pilot studies required (literature doses not directly applicable)
Success Criteria
• Primary endpoint: Blood glucose >300 mg/dL (16.7 mmol/L)
• Secondary markers:
•tPolydipsia/polyuria
•tWeight loss
•tElevated serum biomarkers (TC, AST, TG, LDL)
3.tType 2 Diabetes Induction Protocol[3][4][5]
Mechanism
Combined β-cell dysfunction and insulin resistance (high-fat diet + subtoxic STZ)
Modeling Parameters
SpeciestStrain/Sex/AgetAdministrationtDosage Regimen
MousetC57BL/6 ♀ 10wktIP + HFDt40 mg/kg × 4 days
RattSD/Wistar ♂ 8-10wktIP + HFDt25 mg/kg × 5 days
Validation Criteria
(Identical to Type 1 diabetes model)
Key Advantages
• Established protocol with high reproducibility
• Mimics human disease pathophysiology
• Cost-effective compared to genetic models
Technical Considerations
• STZ stability: Prepare fresh solution in citrate buffer (pH 4.5)
• Monitoring: Daily glucose checks for 2 weeks post-induction
• Housing: Maintain at 22±2°C with 12h light/dark cycle

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Mice: The mice used are male C57BL/6 (10–16 weeks).The age distribution of the mice treated with Streptozocin and ALX, along with the controls, is as follows: n = 7 for Streptozocin xenograft, n = 11 for ALX xenograft, n = 7 for Streptozocin non-transplanted, n = 15 for ALX non-transplanted, and n = 7 for Streptozocin non-transplanted.Male C57BL/6 mice are given an inhalation anesthetic injection via the penile vein, consisting of either 180 mg/kg of streptozocin or 75 mg/mL of ALX. Male C57BL/6 mice make up the control group. Before the drug injection, six hours later, and every day after, blood glucose levels and body weight are recorded.

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Rats: To induce menopause, thirty rats had their ovaries removed. Streptozocin (50 mg/kg) is injected intraperitoneally into rats one week following oophorectomy to cause diabetes mellitus (DM). Three days following the administration of streptozocin, blood glucose levels are measured; values greater than 250 mg/dL are regarded as positive for diabetes.

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Rat type 1 diabetes model assay: Male Wistar rats (180–200 g) are fasted for 12 h, then intraperitoneally injected with Streptozotocin (STZ) (50–70 mg/kg) dissolved in citrate buffer (pH 4.5). Blood glucose is measured every 3 days; rats with fasting blood glucose >16.7 mmol/L for 2 consecutive weeks are considered diabetic. Pancreatic tissue is harvested for insulin content measurement and histopathological analysis [3][5]
Mouse multiple low-dose diabetes model assay: Female C57BL/6 mice (20–25 g) receive intraperitoneal injections of Streptozotocin (STZ) (40 mg/kg/day) for 5 days, dissolved in citrate buffer (pH 4.5). Fasting blood glucose is monitored weekly; mice with glucose >11.1 mmol/L are included in the model. Islet β-cell mass is quantified by immunohistochemistry [5]
Rabbit hyperglycemia assay: New Zealand white rabbits (2–3 kg) are intravenously injected with Streptozotocin (STZ) (80–120 mg/kg) dissolved in physiological saline. Blood glucose and insulin levels are measured at 24, 48, 72 h post-administration [4]

Absorption, Distribution and Excretion
Poor oral absorption (17-25%)
Up to 20% of the drug (or metabolites containing N-nitrosourea groups) is metabolized and/or excreted by the kidneys.
In all these species (mice, rats, cats, monkeys, and dogs), parenteral streptozotocin (STR) is significantly concentrated in the liver and kidneys; for example, in dogs…it remains in the liver for several hours after administration…and is no longer detectable in the blood.
Streptozotocin…is well absorbed in the gastrointestinal tract of mice, but poorly absorbed in monkeys, and negligible in dogs.
Intravenous injection of ¹⁴C-labeled streptozotocin is rapidly cleared from the blood of rats, with less than 1% remaining after 10 minutes.
Streptozotocin (NSC-85998) is rapidly excreted from the urine of test mice; 72% of the injected dose is detectable in the urine after 4 hours. Five urinary metabolites were detected…
After intraperitoneal or intravenous injection of streptozotocin in animals, the drug and its metabolites are rapidly distributed, primarily in the liver, kidneys, intestines, and pancreas, with lower concentrations in skeletal muscle, spleen, lungs, heart, and thymus. The concentrations of the drug or its metabolites in the liver, kidneys, intestines, and pancreas are consistently higher than in plasma. Streptozotocin does not appear to cross the blood-brain barrier in animals or humans; however, in humans, its metabolites readily distribute into the cerebrospinal fluid. …The drug readily crosses the placenta in monkeys.

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Metabolism/Metabolites
Mainly metabolized in the liver
Studies of (14)C-labeled streptozotocin with different positions showed its rapid metabolism in rats…producing metabolites derived from the methylnitrosourea side chain. /SRP: Diazomethane/
/Five urinary metabolites were detected in mouse urine; two of them were α- and β-isomers of the antibiotic.
Streptozotocin and its metabolites have a relatively short distribution phase (half-life of 6 minutes), followed by two elimination phases, representing the active metabolite (β-isomer half-life 3.5 hours, γ-isomer half-life 40 hours).
Streptozotocin is ineffective orally. After intravenous administration, the drug is rapidly cleared from plasma and becomes undetectable after 3 hours. Metabolites can remain detectable in plasma for up to 24 hours. The drug accumulates in certain tissues; the highest concentrations are found in the liver and kidneys, and the pancreas also concentrates streptozotocin. The parent drug and its metabolites are primarily eliminated rapidly by the kidneys; 60% to 70% of the dose is excreted in the urine within 4 hours. Only 10% to 20% of the excreted dose is the parent drug.
Primarily metabolized by the liver.
Elimination pathway: Up to 20% of the drug (or metabolites containing N-nitrosourea groups) is metabolized and/or excreted by the kidneys.
Half-life: 5-15 minutes

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Biological half-life
5-15 minutes
After intravenous infusion of 200-1600 mg/m², the peak plasma concentration is 30-40 μg/mL; the drug half-life is approximately 15 minutes. Only 10-20% of the dose is recovered in the urine.
...Streptozotocin...After intravenous bolus injection, its kinetics in the human body conform to an apparent two-compartment model, with mean rapid and slow distribution half-lives of 4.6 minutes and 40 minutes, respectively. The latter value is 2.5 times higher than previously reported values in patients receiving slow intravenous infusions of streptozotocin.
In 7 patients who received a single intravenous injection of 1.5 g/m², the mean half-life was approximately 40 minutes, and the elimination half-life was approximately 15 minutes.

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Streptozotocin (STZ) has low oral bioavailability in rats (<10%) and exhibits significant first-pass metabolism in the liver[4].
Streptozotocin (STZ) after intravenous injection of 50 mg/kg in rats, the peak plasma concentration (Cmax) reaches 8.5 μg/mL at Tmax = 5 min[4].
Plasma elimination half-life (t1/2) The half-life of streptozotocin (STZ) in rats is 15–20 min[4].
Streptozotocin (STZ) is mainly metabolized in the liver via glutathione conjugation, with less than 5% excreted unchanged in the urine[4].

Toxicity Summary
Streptozotocin is a naturally occurring chemical substance with particularly strong toxicity to insulin-producing β-cells of the pancreas. It is used in medical research to establish animal models of type 1 diabetes (high dose) and type 2 diabetes (multiple low doses). Streptozotocin has a structure similar to glucose and can enter cells via the glucose transporter GLUT2, but it is not recognized by other glucose transporters. This explains its relative toxicity to β-cells, as GLUT2 expression levels are relatively high in these cells. Streptozotocin is an glucosamine-nitrosourea (i.e., alkylated) compound. Like other nitrosourea alkylating agents, it is toxic to cells by damaging DNA, although other mechanisms may also play a role. Streptozotocin has a similar structure to glucose and can enter cells via the glucose transporter GLUT2, but it cannot be recognized by other glucose transporters. This explains its relative toxicity to β-cells, as GLUT2 expression levels are relatively high in β-cells. Streptozotocin is an glucosamine-nitrosourea (i.e., an alkylating agent) compound. Like other nitrosourea alkylating agents, streptozotocin exerts cellular toxicity by damaging DNA, but other mechanisms may also play a role.
Hepatotoxicity
Up to two-thirds of patients treated with streptozotocin experience elevated serum transaminases, but these abnormalities are usually mild, transient, and without symptoms or jaundice. Hepatotoxicity is more common with daily and high-dose administration of streptozotocin, but at high doses, renal and hematologic toxicities often mask liver damage. Two cases of rapidly progressive, fatal acute liver failure have been reported in patients treated with streptozotocin. One patient did not receive other chemotherapy, while the other received fluorouracil concurrently. At the end of the 5-day treatment course, the patient developed fever, anuria, and acute hepatitis (ALT 1280, bilirubin 11.9, prothrombin index 10%, eosinophils 2600/µL). In contrast, there are currently no published case reports of streptozotocin causing self-limiting, clinically significant liver injury. However, due to the rarity of pancreatic islet cell carcinoma and neuroendocrine tumors, the use of streptozotocin is limited.
Probability Score: D (May cause clinically significant liver injury).

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Non-human Toxicity Values
Intraperitoneal LD50 in female mice: 360 mg/kg
Intravenous LD50 in female mice: 275 mg/kg
Intravenous LD50 in male dogs: 50 mg/kg

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Route of Exposure
Intravenous injection. Oral absorption is low (17-25%).

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Symptoms
Overdose symptoms include nausea and vomiting, anorexia, bone marrow suppression, and nephrotoxicity.

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Adverse Reactions
Occupational Hepatotoxicity - Group 2 Hepatotoxicity: Potential toxicity in occupational environments based on cases of human ingestion or animal experimentation.
International Agency for Research on Cancer (IARC) Carcinogen - Group 3: Chemical substances not classified by the IARC.
US National Toxicology Program Carcinogen - Reasonably expected to be carcinogenic to humans.
Streptozotocin (STZ, CAS No. 18883-66-4) is a monofunctional nitrosourea derivative isolated from Streptomyces achromogenes. It has broad-spectrum antibacterial and antitumor properties and is often used to induce diabetes in laboratory animals through its toxic effects on pancreatic β-cells. Streptozotocin (STZ) is a potent alkylating agent known to directly methylate DNA, exhibiting high genotoxicity and causing DNA strand breaks, base unstable sites, unplanned DNA synthesis, DNA adducts, chromosomal aberrations, micronuclei, sister chromatid exchange, and cell death. The antibiotic has been found to be mutagenic in both bacterial and eukaryotic tests. STZ is also carcinogenic; a single dose can induce tumors in the kidneys, livers, and pancreas of rats. Multiple studies have shown that free radicals are involved in the DNA and chromosome damage caused by this compound. Since STZ is used as an antitumor drug, studying its genotoxicity is of great practical significance. This review aims to present our current understanding of the genotoxicity of STZ. [1]

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Interaction
Experiments showed that streptozotocin-induced diabetes in rats enhanced the hepatotoxicity of carbon tetrachloride. Insulin treatment to reverse the diabetic state prevented this enhanced response.
Male Wistar rats were divided into six groups. To induce diabetes, streptozotocin (dissolved in saline) was administered intravenously at the specified times. Manganese was administered intraperitoneally at the specified times for each group. Group 1 was injected with streptozotocin solvent and saline for 2 weeks (control group). Group 2 received streptozotocin injections and was treated with saline for 2 weeks (streptozotocin group). Group 3 received streptozotocin excipient and saline for 1 week, followed by manganese treatment for 2 weeks (saline-manganese group). Group 4 received streptozotocin injections, followed by the same treatment as Group 3 (streptozotocin-manganese group). Group 5 received manganese treatment for 2 weeks, followed by streptozotocin injections, and finally saline treatment for 1 week (manganese-streptozotocin-saline group). Group 6 also received manganese treatment for 2 weeks, followed by streptozotocin injections, and then manganese treatment for 1 week (manganese-streptozotocin-manganese group). After streptozotocin injections, blood glucose levels rose to above 400 mg/dL and stabilized within a few days. The manganese content in the pancreas, spleen, and kidneys of rats in the streptozotocin-manganese treatment group was significantly lower than that in Group 3, while the manganese content in the brain, thymus, and liver remained unchanged. The manganese content in the pancreas, kidneys, and brain of group 6 rats was significantly increased compared to the manganese-streptozotocin-saline group (group 5). The manganese content in the liver was slightly increased, but the manganese content in the thymus and spleen of group 6 rats was lower than that of group 5. In rats, administration of nicotinamide, unsaturated fat diets, vitamin E, or aldose reductase inhibitors interfered with the development of streptozotocin-induced cataracts. Co-administration of streptozotocin with carmustine significantly enhanced the incidence of myelotoxicity and thrombocytopenia; therapeutic activity was not enhanced. For more complete data on interactions of streptozotocin (16 in total), please visit the HSDB record page.

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Non-human toxicity values
Intraperitoneal LD50 of female mice: 360 mg/kg
Intravenous LD50 of female mice: 275 mg/kg
Intravenous LD50 of male dogs: 50 mg/kg

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Streptozotocin (STZ) exhibits selective toxicity to pancreatic β-cells: In rats, doses ≥ 50 mg/kg (intraperitoneal injection) induce irreversible β-cell destruction [3][5]
The intraperitoneal LD50 of streptozotocin (STZ) is 150 mg/kg in mice and 200 mg/kg in rats [5]
Streptozotocin (STZ) causes mild hepatotoxicity in rats at doses > 60 mg/kg, accompanied by a transient increase in serum ALT/AST [5]
Streptozotocin (STZ) It is mutagenic in bacterial and mammalian cell systems and may be genotoxic in vivo [1]

[1]. Mutat Res . 2002 Dec;512(2-3):121-34.

[2]. Biochem Mol Biol Int . 1996 Aug;39(6):1229-36.

[3]. Diabetes . 1967 Jan;16(1):51-6.

[4]. Tohoku J Exp Med . 1989 Oct;159(2):83-90.

[5]. Comp Med . 2011 Aug;61(4):356-60.

[6]. Anal Biochem . 2016 Jul 1:504:38-40.

Therapeutic Uses
Antibiotic, aminoglycoside; antibiotic, antitumor drug… A specific β-cytotoxin, therefore it can be used to treat metastatic pancreatic islet cell tumors. It has been found to be effective against Hodgkin's lymphoma, other lymphomas, and occasionally melanoma and malignant carcinoids… Massive watery diarrhea in patients with pancreatic cholera (Vina-Morrison syndrome, secretory diarrhea) caused by metastatic non-β-cell tumors can be relieved by hepatic artery infusion of streptozotocin. Drug Use (Veterinary):… In laboratory animals, streptozotocin has been shown to induce diabetes. Drug Warnings Patients with a history of renal impairment should not receive streptozotocin treatment. Streptozotocin often causes abnormalities on liver scans. This suggests that minor abnormalities may be misattributed to inherent liver disease. Pharmacodynamics Streptozotocin is an antitumor antibiotic composed of a nitrosourea moiety linked between a methyl group and glucosamine. Streptozotocin is indicated for the treatment of metastatic pancreatic islet cell carcinoma. Streptozotocin inhibits DNA synthesis in both bacterial and mammalian cells. In bacterial cells, specific interactions with cytosine residues lead to DNA degradation. The biochemical mechanisms leading to mammalian cell death are not fully elucidated; the concentrations at which streptozotocin inhibits cell proliferation are far below those required to inhibit DNA precursor incorporation into DNA or to inhibit multiple DNA synthases. Although streptozotocin inhibits cell entry into mitosis, it is not particularly sensitive to its lethal effects at any particular stage of the cell cycle. Streptozotocin (STZ) is a naturally occurring nitrosourea compound isolated from Streptomyces colorlessis [3]. Streptozotocin (STZ) induces type 1 diabetes in animals by alkylating pancreatic β-cell DNA, resulting in cell death and insulin deficiency [3][5]. Streptozotocin (STZ) has been widely used as a research tool for constructing experimental diabetes models in rodents and rabbits [3][4][5].
Streptozotocin (STZ) exerts its cytotoxic and mutagenic effects through the generation of reactive oxygen species and DNA alkylation [1][2].
Due to the cytotoxic and mutagenic effects of streptozotocin (STZ), it is not currently used clinically. Its selective toxicity to β cells and genotoxicity [3][5]

C8H15N3O7

265.22

265.091

C, 36.23; H, 5.70; N, 15.84; O, 42.23

18883-66-4

29327

White to off-white solid powder

1.9±0.1 g/cm3

121 °C (dec.)(lit.)

1.670

-1.33

5

8

2

18

315

5

O1[C@@]([H])([C@@]([H])([C@]([H])([C@@]([H])([C@@]1([H])C([H])([H])O[H])O[H])O[H])N([H])C(N(C([H])([H])[H])N=O)=O)O[H]

ZSJLQEPLLKMAKR-GKHCUFPYSA-N

InChI=1S/C8H15N3O7/c1-11(10-17)8(16)9-4-6(14)5(13)3(2-12)18-7(4)15/h3-7,12-15H,2H2,1H3,(H,9,16)/t3-,4-,5-,6-,7+/m1/s1

1-methyl-1-nitroso-3-[(2S,3R,4R,5S,6R)-2,4,5-trihydroxy-6-(hydroxymethyl)oxan-3-yl]urea

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.  (2). This product is not stable in solution, please use freshly prepared working solution for optimal results.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.08 mg/mL (7.84 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (7.84 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (7.84 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: Saline: 30 mg/mL

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Solubility in Formulation 5: 100 mg/mL (377.05 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C).

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 (Please use freshly prepared in vivo formulations for optimal results.)