Effective Dose Regimen of Streptozotocin for Inducing Diabetes in a Rat Model

Abstract

Background: Diabetes mellitus (DM) is a metabolic disorder characterized by an elevated blood sugar level due to problems with insulin synthesis, effect, or both. Various clinical signs follow DM: Hyperglycemia, polydipsia, polyuria, and polyphagia. Worldwide prevalence is high and predicted to be 592 million by 2035. Animal models are used in the study of diabetes due to ethical issues. Although the streptozotocin (STZ) model is frequently used, it is unreliable due to unexplained acute toxicity and effective dose variability. Objectives: This research was conducted to determine the effective dose regimen of STZ for inducing diabetes in Wister rats. Methods: A total of 28 male Wistar rats (160-190 g) were randomly divided into 4 groups (each 7 rats) and monitored for 21 days after diabetes induction with STZ: Control (CTR), diabetics (DIA)1 (60 mg/kg STZ), DIA2 (60 mg/kg STZ twice at 0 and 24 hours), and DIA3 (60 mg/kg STZ thrice at 0, 24 and 48 hours). Plasma glucose was determined with a glucometer. Body weights, feed intake, and fecal output were weighed with a digital balance, while water intake and urine output were measured with a measuring cylinder. Analyses of data obtained were performed using a one-way ANOVA and Tukey’s test at a significance level of P≤0.05. Results: There was a significant (P<0.05) decrease in body weight of the diabetic groups (-15.53%±1.2%, -26.8%±1.2%, -28.5%±1.9%) compared to the CTR (10.5%±2.5%). There was a significant (P<0.05) increase in fasting blood glucose concentrations (135.2±9.0, 273.2±6.5, 257.0±5.3 mg/dL) in the people with diabetes compared to the CTR (79.3±1.1 mg/dL). Water intake (56.9±0.9, 72.1±1.7, 77.8±5.5 mL), feed intake (19.4±0.6, 23.3±1.9, 42.1±2.1 g), voided urine (6.34±0.1, 8.39±0.88, 9.8±0.50 mL) and voided feces (10.4±0.26, 11.7±0.43, 8.5±0.17 g) in the diabetic groups increased significantly (P<0.05) compared to the CTR (26.5±0.8 mL, 13.4±0.3 g, 1.84±0.08 mL, and 6.5±0.33 g, respectively). Conclusion: The dose regimen of 60 mg/kg STZ administered intraperitoneally twice (24 hours apart) sustained diabetes for 21 days. We recommend adopting this dose regimen in STZ-induced diabetic studies in male Wistar rats.