Effects of streptozotocin dosing on the disease state of streptozotocin-induced diabetic rats

The effects of varying dosages of intraperitoneal (i.p.) injections of streptozotocin (STZ) on the disease state of STZ-induced diabetic rats were assessed. When administered as a single i.p. injection, 50 mg.kg-1 STZ is considered safe. However, it is necessary to set the dosage interval to approximately 7 days in the case of 2 i.p. injections of 50 mg.kg-1 STZ. The serum levels of total bile acids (TBA), which are ligands of constitutive androstane receptors, related to the regulation of mRNA, expression of cytochrome P450, conjugation enzymes, and transporters, differed between rats that received single and double STZ administrations. TBA levels in the model rats should be stable otherwise it could lead to differences in regulation of mRNA expression. When a single dose of STZ was administered, the TBA levels stabilized within 4 weeks of administration. However, when 2 doses of STZ were administered, TBA levels stabilized within 2 weeks of administration.