The Effect of Diosmin-Hesperidin Combination on Blood Glucose and Hba1c Levels in HIV-Protease Inhibitor Treated Rattus Norvegicus

Abstract

Available reports show that medication with HIV protease inhibitors (HIV-PIs) can lead to high blood glucose in HIV positive patients. There is therefore a need to find ways of mitigating this hyperglycemic effect as a result of treatment with HIV-PIs. We assessed the effect of administration of the flavonoids Diosmin and Hesperidin on HIV protease inhibitor (HIV-PIs) induced elevated blood glucose and HbA1c levels in Rattus norvegicus albinus (Wistar rats). Seventy-two Wistar rats were randomly assigned to six groups of twelve rats each. Group 1 was a Control. The other five groups (2-6) were treated with LPT/RTV(2/0.5mg/kg), ATV/RTV(3mg/1 mg/kg), LPV/RTV plus DIOS/HES(2/0.5 mg /kg plus 4.5/0.5 mg/kg), ATV/RTV plus DIOS/HES(3/1mg per kg plus 4.5/0.5 mg /kg), and DIOS/HES(4.5/0.5mg/kg), respectively, administered twelve hourly. The blood glucose and HbA1c concentrations were measured, analyzed, and presented using descriptive statistics and one-way ANOVA. The Control group, DIOS/HES, and the ATV/RTV+DIOS/HES-treated groups did not show any significant differences in their group mean blood glucose levels from the second week of treatment to the end of the study. The ATV/RTV (5.95±2.15 mmol/L on week 3), LPV/RTV (5.14±0.92 mmol/L on week 3), and LPV/RTV+DIOS/HES (5.30±1.72 mmol/L on week 3) treated groups had significantly elevated group mean blood glucose levels on the third week of the study compared to the control group (3.88±0.42 mmol/L. The HIV- rotease inhibitors increased group mean HbA1c levels with the LPV/RTV treated group increasing from 4.67± 0.16 percent on day 0 to 5.45±0.77 percent on day 42 (p<0.01) and ATV/RTV treated group mean HbA1c level increasing from 4.52±0.16 percent on day 0 to 5.13±0.53 percent on day 42 (p<0.01) while the DIOS/HES group mean HbA1c levels decreased significantly (4.73±0.16 percent at day 0 to 3.35±0.48 percent on day 42, p<0.001). The results demonstrated that the co-administration of ATV/RTV with DIOS/HES significantly reduced the blood glucose-elevating effects of the ATV/RTV combination. The co-administration of the flavonoids with HIV-PIs also reduced the blood HbA1c levels. We recommend further studies on the effects of Hesperidin and Diosmin on blood glucose and HbA1c in humans on HIV-PIs.