Time course effects of 5,5-dihydroxyl pyrimidine-2,4,6-trione (alloxan) as a diabetogenic agent in animal model

Abstract

Objective: The use of alloxan as a diabetogenic agent at 150 mg/kg BW has been characterized by low percentage induction and instability of the hyperglycemia induced. The present study examined its time course effects with a view to suggesting the probable effective dose of the compound for animal studies.

Methods: Forty adult Wistar rats were equally randomized into two groups (I and II) and were injected with single intraperitoneal dose of alloxan, 170 and 200 mg/kg BW respectively. Blood glucose concentration (BGC) was monitored in consecutive phases of hourly for 3 h, 3 h interval for 15 h, 6 h interval for 12 h and 9 h after. Changes with time in biomarkers of oxidative stress (SOD, CAT, GST and MDA) and pancreas histopathology were studied.

Results: Alloxan at the evaluated doses produced a multiphasic blood glucose response. One hour post alloxan injection, 90% of group I and 85% of group II animals exhibited diabetic hyperglycemia (glucose level ≥ 200 mg/dL). Groups I and II respectively produced peak levels of hyperglycemia (586.8 and 575.9 mg/dL) at 9 and 12 h post alloxan administration. Hypoglycemia which is characteristic of experimental diabetes was noted between the 15th and 21st hour in both groups (I and II) and resulted in 5 and 10% mortality respectively. At 36th hour, hyperglycemia was restored and apparently sustained. Changes in biomarkers of oxidative stress showed patterns similar to that of blood glucose, and the histopathological examination of the pancreas mainly indicated focal area of a necrotic islet and multifocal area of mild infiltration in both groups.

Conclusion: The data obtained shows that alloxan at the investigated doses produced sustained hyperglycemia at 21st and 24th hour post administration, and 170 mg dosage of the compound is apparently a better diabetogenic dose, particularly in terms of reduced animal mortality.

Keywords: Alloxan, Diabetogenicity, Diabetes, Effective dose