Keywords
Abstract
Rauwolfia serpentina Benth. ex Kurz is a tropical bushy plant that produces more than 50 different alkaloids with antiarrhythmic and hypotensive effect. The new technology for cultivation and production of Rauwolfia serpentina tissue culture was successfully developed in the Institute of Molecular Biology and Genetics of the NAS of Ukraine, that allows to regard the Rauwolfia serpentina biomass as a prospective raw material for the production of medicines and biologically active substances. However, their use in medicine requires comprehensive trials, first of all the acute and subacute toxicity study of the biomass extracts. The aim of the study – to evaluate an acute and subacute toxicity of the biomass extract of highly productive Rauwolfia serpentina K-27M cell line. White outbred mice with a weight of 18–25 g were used. The acute toxicity was assessed after intragastric administration of the extract in a volume of no more than 0.5 mL. Toxicity was calculated by V. Prozorovski method 14 days after a single administration. To assess the subacute toxicity the mice were randomized into 3 groups. The doses of 15 and 45 mg/kg of the extract were administered to the groups 1 and 2, respectively, while the group 3 (control) was injected with distilled water. An increased activity of mice, convulsions, catalepsy, and subsequent death over 1 hour period were observed, when 501 to 1000 mg/kg of the extract were administrated. When lower doses (250–398 mg/ kg) were used, reduced activity, grooming, tail hypertonus, increased breathing rate and aggression were observed, however the doses were not fatal to animals and the normal state was recovered after 2 hours. After the administration of the extract at doses below or equal to 250 mg/kg no negative effects were observed. Since high mortality and/or significant signs of intoxication (gastrointestinal atony, flatulence, and blood filling of the parenchymal organs) were observed in the subacute toxicity study, the doses were halved, i.e. to 7.5 mg/kg for group 1 and 22.5 mg/kg for group 2. No mortality was observed, however the following symptoms of subacute toxicity were evident: reduced body weight, severe abdominal distension, drowsiness, and decreased motor activity. No significant differences in the counts of white and red blood cells, and platelets were found between all groups of mice. However, a significant increase in the neutrophils and eosinophils counts was found in the group 1; while in the group 2, the basophil count was elevated. The LD50 value of the extract of biomass of Rauwolfia serpentina K-27M cell line was determined to be (450 ± 35) mg/kg (toxicity class III – moderate toxicity). The results of biochemistry and haematology tests may indicate the inflammatory processes in the intestine and the allergenic potency of the extract.