Temporal Effect of Varying Doses of Clonidineon the Fasting Blood Glucose Levels of Sprague Dawley Rats

Abstract

Background Primarily used as a centrally-acting anti-hypertensive drug, clonidine has also been shown to affect blood glucose determinants by acting on peripheral α-2 adrenoreceptors. However, the studies which investigate the effect of clonidine on blood glucose levels yielded conflicting results depending on conditions applied. Methods Thirty-five (35) adult male SpragueDawley rats weighing 140-330 grams were randomly and equally assigned to five treatment groups of varying clonidine doses: 1, 2, 4, 7μg/kg and 0.9% NaCl (control). The doses were administered intra-peritoneally after fasting the rats for 18 hours. Whole blood samples (at least 1 μl) were obtained via tail pricking/tail lancing and measured for glucose levels using a commercially available glucometer (One-touch Ultra ®) 1 hour before injection to get baseline blood glucose levels and every hour for 8 hours after injection to measure changes in blood glucose levels. The rats remained fasted until after the 8-hour monitoring period. Data were analyzed using t-test, Analysis of Variance(ANOVA) and Tukey LSD at 95% confidence interval (α=0.05). Area under the curve (AUC) reflecting the cumulative blood glucose level within the first 8-hour monitoring period for each dosage was computed. Results Significant differences among fasting blood glucose levels of 2, 4, 7 μg/kg and control groups were observed at the 1 to 4 hour after injection, with the treatment groups having higher glucose levels than the control group. No significant difference was observed between the 1 μg/kg group and control group. At the 5 hour onwards, no significant difference was noted among treatment means. Cumulative dose effect of clonidine (AUC) showed a significant rise in glucose at 4 and 7 μg/kg with apparent saturation at 4 μg/kg when plotted in a dose-response curve. Conclusions Intraperitoneal administration of clonidine significantly increases blood glucose levels when administered at 2, 4 and 7 μg/kg with peak effect at 1 to 3 hour post injection and no significant difference starting at 5 hour post-injection onwards. Optimal dosage is found to be at 4 μg/kg.