Abstract

Doses and route of administration in chemical diabetes modeling critically shape the performance of diabetes models, but head-to-head, dose-matched comparisons without additional drugs are limited. This study aimed to compare glycemic, body weight, and oxidative stress induced by two doses and two routes of administration of streptozotocin (STZ) and Alloxan (ALX) in male Wistar rats. A total of 56 male Wistar albino rats (200 – 250 g) were included in the study and randomized into eight groups (n = 7 per group). STZ and ALX at doses of 45 or 60 mg/kg were administered intravenously (i.v.) and intraperitoneally (i.p.). Blood glucose was measured at baseline and every 3 days for 21 days; body weight was monitored; and oxidative balance was assessed by Total oxidant status (TOS) and Total antioxidant status (TAS). Group and time effects were analyzed using repeated measures statistics using SPSS 30. All groups exceeded 200 mg/dL on day 3, confirming diabetes. Among the STZ arms, 60 mg/kg i.p. produced the highest glycaemia from day 9 to day 15, after which the 45 mg/kg i.v. arm reached comparable or higher values; the 45 mg/kg i.p. arm remained substantially lower throughout. In the ALX arms, dose was the primary determinant: 60 mg/kg i.p. produced the highest and most sustained hyperglycemia from day 6; whereas at 45 mg/kg blood glucose did not differ significantly between the i.v. and i.p. routes. Weight loss was greatest in the 60 mg/kg i.v. group. TOS was greater with ALX compared to STZ. TOS was lowest with 45 mg/kg i.v. ALX. TAS was higher with ALX than with STZ at 45 mg/kg, but not at 60 mg/kg. No mortality occurred over the 21-day period. In this dose-matched comparison, dose is the primary determinant of model strength, and route of administration modulates the response more for ALX than for STZ. Diabetes was diagnosed starting on day 3 with both doses and routes of administration. In practice, 60 mg/kg i.p. ALX and STZ produce consistently high blood glucose levels suitable for diabetes induction, while i.v. administration promotes early peaks and i.p. administration promotes a sustained glycemic load. These findings provide practical guidance for selecting agent, dose, and route in future preclinical diabetes studies.

Key words: Streptozotocin, alloxan, rat, diabetes model, dose-response, oxidative stress