A diabetogenic agent which targets beta cells
Streptozocin, a potent DNA-methylating antibiotic, is a naturally occurring nitrosoamide used for extensively to produce diabetes in experimental models.[1]
In vitro, STZ was toxic with IC50 values of 11.7, 904 and 1024 μg/ml for HL60, K562 and C1498 cells respectively.[3]
In vivo efficacy test it shown that when combined with a protocol for induction of diuresis, dogs were treated safely with 500 mg/m2 of streptozocin, intravenously, every 3 weeks, and it may be have a potential efficacy on the treatment of dogs with metastatic pancreatic islet cell tumors.[1]
In vivo experiment it indicated that mice were administrated streptozocin with 65 mg/kg intraperitoneally for 8-11 days or 14-17 days, streptozocin improved the impaired development of preimplantation embryos on 8-11 days. However, after 14-17 days, the incidence of degenerated embryos was increased in both streptozocin-treated mice groups.[2] Treatment with 60 mg/kg of streptozocin intravenously also induces an early hyperglycaemia when the hepatic glycogen storage is almost depleted that is during the fasting state.[4] For the treatment of advanced islet-cell carcinoma, the combination of streptozocin and doxorubicin is more efficious than the current standard regimen of streptozocin plus fluorouracil.[5] There is little value for patients with malignant carcinoid tumors by combination treatment with streptozocin and 5-fluorouracil.[6]
参考文献:
[1].Moore AS, et al. Streptozocin for treatment of pancreatic islet cell tumors in dogs: 17 cases (1989-1999). J Am Vet Med Assoc. 2002 Sep 15;221(6):811-8.
[2].Veselá J, et al. Subdiabetogenic streptozocin treatment impairs preimplantation development of mouse embryos. Physiol Res. 1993;42(1):23-7.
[3].Diab RA, et al. Immunotoxicological effects of streptozotocin and alloxan: in vitro and in vivo studies. Immunol Lett. 2015 Feb;163(2):193-8.
[4].Wong KK. Reduction by streptozocin of blood glucose utilization during the appearance of the streptozocin induced early hyperglycaemia in fasting rats. Biochem Mol Biol Int. 1996 May;39(1):191-5.
[5].Moertel CG, et al. Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med. 1992 Feb 20;326(8):519-23.
[6].Oberg K, et al. Cytotoxic treatment in patients with malignant carcinoid tumors. Response to streptozocin--alone or in combination with 5-FU. Acta Oncol. 1987;26(6):429-32.
Streptozocin 是一种有效的 DNA 甲基化抗生素，是一种天然存在的亚硝基酰胺，在实验模型中广泛用于产生糖尿病。[1]
在体外，STZ 对 HL60、K562 和 C1498 细胞的 IC50 值分别为 11.7、904 和 1024 μg/ml。[3]
体内功效测试表明，当与诱导利尿方案相结合时，狗可以安全地每 3 周静脉注射 500 mg/m2 链佐星，并且它可能对治疗患有转移性胰岛细胞瘤的狗。[1]
体内实验表明，给小鼠腹腔注射65 mg/kg链脲佐菌素8-11天或14-17天，链脲佐菌素在8-11天改善着床前胚胎发育受损。然而，在 14-17 天后，两个接受链脲佐菌素治疗的小鼠组的退化胚胎发生率都增加了。[2] 静脉注射 60 mg/kg 链佐佐星也可诱导早期高血糖症，此时肝糖原储存在禁食状态下几乎耗尽。[4]对于晚期胰岛细胞癌的治疗，链佐星和多柔比星的组合比目前链佐星加氟尿嘧啶的标准方案更有效.[5]链脲佐菌素与5-氟尿嘧啶联合治疗恶性类癌患者价值不大。[6]
| Cell experiment [1]: | |
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Cell lines |
islet cells |
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Preparation Method |
Monolayer cultures of islet cells from neonatal rats were exposed to concentrations of MNU and STZ (Streptozocin) of 1, 2, 5, or 10 mM, and the activity of the enzyme was assayed. |
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Reaction Conditions |
1, 2, 5, or 10 mM |
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Applications |
Streptozocin is toxic to cultured p-cells at a concentration of 1 mM. |
| Animal experiment [2]: | |
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Animal models |
Female mice |
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Preparation Method |
Female mice received a single subdiabetogenic dose of streptozocin (65 mg/kg intraperitoneally) 8-11 days or 14-17 days before fertilization. |
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Dosage form |
65 mg/kg; i.p. |
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Applications |
Morphological analysis of preimplantation embryos collected on day 3 of pregnancy revealed significant changes in the distribution pattern of preimplantation embryo stages recovered from streptozocin-treated females. |
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参考文献: [1]. Wilson GL, et al. Mechanisms of nitrosourea-induced beta-cell damage. Activation of poly (ADP-ribose) synthetase and cellular distribution. Diabetes. 1988 Feb;37(2):213-6. [2]. Veselá J, et al. Subdiabetogenic streptozocin treatment impairs preimplantation development of mouse embryos. Physiol Res. 1993;42(1):23-7. |
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