The synthesis of [14C]streptozotocin and its distribution and excretion in the rat

Abstract

[14C]Streptozotocin was synthesized specifically labelled at three positions in the molecule. The biological activity ofsynthetic streptozotocin was characterised by studies in vivo ofits diabetogenic activity and its dose-response curves. After this characterization the excretion pattern of all three labelled forms of streptozotocin was studied. With [1-14C]-streptozotocin and [2'-14C]streptozotocin the injected radioactivity was excreted (approx.70% and 80% respectively) mainly in the urine, the greater part of the excretion occurring in the first 6h period; small amounts (approx. 9% and 8 % respectively) were found in the faeces. In contrast, with [3'-methyl-'4C]streptozotocin a much smaller proportion (approx.42 %) of the injected radioactivity was excreted in the urine, the major proportion appearing in the first 6h, whereas approx. 53 % of the injected radioactivity was retained in the carcasses. In whole-body radioautographic studies very rapid renal clearance and hepatic accumulation of the injected radioactivity was observed with all three labelled forms of the drug. There was some evidence for biliary and intestinal excretion. Major differences were apparent in the tissue-distribution studies, with each of the three labelled forms, particularly with [3'-methyl-14C]streptozotocin. There was no accumulation of [1-_4C]streptozotocin in the pancreas for the 6h period after administration. However, with [3'-methyl-14C]-streptozotocin (and also [2'-'4C]streptozotocin) there was evidence of some pancreatic accumulation after 2h. The results indicate that streptozotocin is subjected to considerable metabolic transformation and to rapid renal clearance. The implication of these suggestions is evaluated with particular reference to the diabetogenic action of streptozotocin.

Molecular evidence for a role for K+-Cl− cotransporters in the kidney

“…We studied five experimental groups. Group 1 consisted of rats given a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg body wt, Sigma) (29,42). Seventy-two hours after STZ administration, the blood glucose concentration was determined (Accu-Chek sensor comfort, Roche Diagnostics), and only rats with a postprandial blood glucose level of Ͼ20.0 mmol/l were considered diabetic and were followed for the next 4 wk.…”

Hyperglycemia induces apoptosis in rat liver through the increase of hydroxyl radical: new insights into the insulin effect

“…injection of an equal volume of citrate buffer. It is known that STZ is excreted within 48 h from injection and therefore cannot be a direct effect of oxidative stress (Karunanayake et al 1974). Fifteen days after STZ injection, a time when the toxic effect of the drug on the liver would have disappeared (Carnovale & Rodriguez Garay 1984, Carnovale et al 1986), blood samples were obtained from the tail vein, and glucose concentrations were measured by means of a Surestep glucometer (Glucostix, Bayer HealthCare).…”

Involvement of inducible nitric oxide synthase in hydroxyl radical-mediated lipid peroxidation in streptozotocin-induced diabetes

“…Such results clearly link iNOS overexpression with increased free radical formation and lipid peroxidation in the disease, which might be involved in the progression of diabetes. iNOS-mediated free radical production in diabetes [31]. Development of the disease was confirmed three days later with a urinary glucose test strip (Chemstrip uGK, Roche).…”