The interactions of stevioside and bile acids with cardioactive drugs

Zdenko Tomic, Boris Milijasevic, Ana Sabo, Aleksandar Raskovic, Momir Mikov, Velibor Vasovic. Faculty of Medicine, University of Novi Sad, Department of Pharmacology, toxicology and clinical pharmacology, Serbia

The interaction of aqueous solutions of stevioside (ST) and bile acids with cardioactive drugs was studied in rats by registering changes in their electrocardiograms (ECG).

In our research 72 Wistar rats were used. The animals were divided into 2 groups. In first group was 54 animals which received daily doses of 20 mg/kg intraperitoneal (i.p.) of ST and in second group were 18 animals which received i.p. physiological solution (C). 18 rats from first group recived i.p. a single dose of 4 mg/kg of monoketocholic acid methyl ester (ME) while 18 rats recived i.p. a single dose of 4 mg/kg of sodium salt of the same bile acid (MKHNa), 30 minutes before cardioactive drug infusion.The pretreatment period lasted for five days, after which all animals were anaesthetized and connected to the ECG for the first recording. The jugular vein was prepared and connected to an infusion pump to administer one of the drugs: adrenaline (0.1 mg/ml), verapamil (2.5 mg/ml) or metoprolol (1 mg/ml). The events observed on ECG recordings were the first myocardial reaction to drug infusion, the second reaction, and toxicity effect. Statistical analysis was performed by Student’s t-test for small independent samples. P values less than 0.05 and 0.02 were taken as significant.

In the control animals, adrenaline induced a decrease in heart rate frequency at a dose of 0.094±0.007 mg/kg, while with ST pretreated rats this effect appeared significantly earlier (at a dose of 0.018±0.005 mg/kg). No toxic effect of adrenaline was observed, neither in control or ST pretreated group. There was no myocardial reaction to metoprolol in all of the examined groups. Stevioside induced a significant increase in myocardial sensitivity to verapamil, but no toxic effect was observed in any of the cases. A similar conclusion also holds for the interaction with MKHNa, whereas ME caused an increase in the toxicity of verapamil.

This research was financially supported by Ministry of Science, Republic of Serbia, project no 41012.