Degradation products of streptozotocin do not induce hyperglycemia in rats

Lee, Jooyoung; Kim, Mee-Jeong; Moon, Chang-Hyun; Chung, Jin

doi:10.1016/0006-2952(93)90657-i

Cited by 12 publications

(10 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NO was found to be liberated in β cells only when STZ had been metabolized inside the cell (Kröncke et al 1995). The pharmacokinetics of STZ have been explored so far in rats after the parenteral administration, showing that 30% of the compound is eliminated within the first hour in the form of the degrading products and partly as the unchanged molecule (Lee et al 1993), while in cell culture its biological half-life was shown to be approximately 19 minutes (Jensen et al 1977). Some of its cleavage/degradation products, which chemical structure has not been clearly defined yet, were shown to have some biologic, although not diabetic, activity (Lee et al 1993), and a capability of crossing cell membranes (Goud et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Rat brain glucose transporter-2, insulin receptor and glial expression are acute targets of intracerebroventricular streptozotocin: risk factors for sporadic Alzheimer’s disease?

et al. 2017

View full text Add to dashboard Cite

Accumulated evidence suggests that the insulin-resistant brain state and cerebral glucose hypometabolism might be the cause, rather than the consequence, of the neurodegeneration found in a sporadic Alzheimer's disease (sAD). We have explored whether the insulin receptor (IR) and the glucose transporter-2 (GLUT2), used here as their markers, are the early targets of intracerebroventricularly (icv) administered streptozotocin (STZ) in an STZ-icv rat model of sAD, and whether their changes are associated with the STZ-induced neuroinflammation. The expression of IR, GLUT2 and glial fibrillary acidic protein (GFAP) was measured by immunofluorescence and western blot analysis in the parietal (PC) and the temporal (TC) cortex, in the hippocampus (HPC) and the hypothalamus. One hour after the STZ-icv administration (1.5 mg/kg), the GFAP immunoreactivity was significantly increased in all four regions, thus indicating the wide spread neuroinflammation, pronounced in the PC and the HPC. Changes in the GLUT2 (increment) and the IR (decrement) expression were mild in the areas close to the site of the STZ injection/release but pronounced in the ependymal lining cells of the third ventricle, thus indicating the possible metabolic implications. These results, together with the finding of the GLUT2-IR co-expression, and also the neuronal IR expression in PC, TC and HPC, indicate that the cerebral GLUT2 and IR should be further explored as the possible sAD etiopathogenic factors. It should be further clarified whether their alterations are the effect of a direct STZ-icv toxicity or they are triggered in a response to STZ-icv induced neuroinflammation.

show abstract

Section: Discussionmentioning

confidence: 99%

Rat brain glucose transporter-2, insulin receptor and glial expression are acute targets of intracerebroventricular streptozotocin: risk factors for sporadic Alzheimer’s disease?

et al. 2017

View full text Add to dashboard Cite

show abstract

“…in PBS). 10,27 There is, however, a time-dependent decrease in the stability of STZ in a neutral pH buffer, 27 so the time between mixing and injection for each treated mouse should be minimized. A previous study showed a circadian rhythm for STZ response, with the largest induction of experimental diabetes observed when STZ was delivered at 16:00 h, 28 which is the time that we performed our MLD-STZ injections.…”

Section: Discussionmentioning

confidence: 99%

Streptozotocin is equally diabetogenic whether administered to fed or fasted mice

et al. 2013

View full text Add to dashboard Cite

Streptozotocin (STZ) is a selective pancreatic β cell toxin used to generate experimental hyperglycemia in rodent models. Several laboratory animal protocols suggest that STZ be administered to fasted rodents to minimize competition between STZ and glucose for low affinity GLUT2 transporters on β cells. However, whether the diabetogenic effects of multiple low dose (MLD)-STZ administration are enhanced by fasting has not been addressed. Given that repeated bouts of fasting can cause undue metabolic stress in mice, we compared the efficacy of MLD-STZ injections (50 mg/kg body weight daily for 5 days) to induce experimental hyperglycemia in both NOD/SCID/γchainnull and C57BL/6J mice that were either ad libitum fed (STZ-Fed) or that had been fasted for 6 h (STZ-Fasted) prior to the time of STZ administration. Both STZ-Fed and STZ-Fasted mice had significantly worse glucose tolerance than vehicle-treated control mice 10 days after initiation of the MLD-STZ regimen. In C57BL/6J mice, fasting glucose levels, serum insulin levels, β cell mass, and glucose disposal during intraperitoneal glucose tolerance tests (IPGTTs) were indistinguishable between STZ-Fed and STZ-Fasted mice 20 days after MLD-STZ. The glucose intolerant phenotypes persisted for 20 weeks thereafter, irrespective of whether C57BL/6J mice were fed or fasted at the time of STZ injections. However, STZ-Fasted C57BL/6J mice experienced significant weight loss during the repeated bouts of fasting/re-feeding that were required to complete the MLD-STZ protocol. In summary, induction of experimental hyperglycemia can be achieved using the MLD-STZ protocol without repeated bouts of fasting, which have the potential to cause metabolic stress in laboratory mice.

show abstract

“…Such compounds may be available in soluble forms that could be loaded into the DC Bead, but as the bead is a hydrogel material possessing many hydroxyl groups within the network structure, the potential for reaction with the alkylating agents is high, generating degradation products in situ and chemically modifying the bead structure. For instance, streptozotocin is a reactive molecule, readily decomposing in water to form isocyanate-bearing sugars and carbonium ions, among other degradants, both of which could readily react with the beads [23]. This is not a desired attribute for an ideal delivery system, as it is unknown whether the degradation products possess any anticancer activity or, indeed, whether they pose any additional risk to the patient.…”

Section: Bead and Interactions With Other Drug Typesmentioning

confidence: 98%

DC Bead™: a major development in the toolbox for the interventional oncologist

Lewis

2009

Expert Review of Medical Devices

View full text Add to dashboard Cite

The DC Bead is fast becoming the product of choice for use in the treatment of intermediate-stage hepatocellular carcinoma. It is a drug-eluting embolization system that is delivered intra-arterially and combines the effects of physical occlusion of the blood supply to a tumor with the local controlled delivery of a chemotherapeutic agent. While not suitable for use with all drugs, the components of this device enable rapid loading and sustained elution of therapeutic amounts of a range of clinically relevant anticancer compounds. Extensive preclinical testing has demonstrated the reproducibility and reliability of the device, together with reduced systemic drug exposure and sustained local drug delivery. Moreover, these attributes are translating into the clinic as significant benefits to patients with many types of liver tumors.

show abstract

Degradation products of streptozotocin do not induce hyperglycemia in rats

Cited by 12 publications

References 5 publications

Rat brain glucose transporter-2, insulin receptor and glial expression are acute targets of intracerebroventricular streptozotocin: risk factors for sporadic Alzheimer’s disease?

Rat brain glucose transporter-2, insulin receptor and glial expression are acute targets of intracerebroventricular streptozotocin: risk factors for sporadic Alzheimer’s disease?

Streptozotocin is equally diabetogenic whether administered to fed or fasted mice

DC Bead™: a major development in the toolbox for the interventional oncologist

Contact Info

Product

Resources

About