Determination of effective dose combination of Azadirachta indica leaf extracts and diminazene diaceturate in the treatment of experimental Trypanosoma brucei brucei infection in rats

Abstract

This study investigated the effective dose of methanolic Azadirachta indica leaf extracts, MAILE, combined with diminazene diaceturate, DDA, in the treatment of experimental Trypanosoma brucei brucei infection in rats. Acute toxicity study of the drug and extract combinations was carried in non-infected rats. Eleven different groups of ten rats each were used. Ten out of the eleven groups were infected with T. brucei brucei and used to determine the effective dose of MAILE and DDA combination to be used in the treatment of the infection. All the infected rats were treated, viz, 7.0 mg/kg body weight (bw) DDA plus 500 mg/kg bw MAILE (group 1); 7.0 mg/kg body bw DDA plus 250 mg/kg bw MAILE (group 2); 7.0 mg/kg body bw DDA plus 125 mg/kg bw MAILE (group 3); 3.5 mg/kg body bw DDA plus 500 mg/kg bw MAILE (group 4); 3.5 mg/kg body bw DDA plus 250 mg/kg bw MAILE (group 5); 3.5 mg/kg body bw DDA plus 125 mg/kg bw MAILE (group 6); 1.8 mg/kg bw DDA plus 500 mg/kg bw MAILE (group 7); 1.8 mg/kg bw DDA plus 250 mg/kg bw MAILE (group 8); 1.8 mg/kg body bw DDA plus 125 mg/kg bw MAILE (group 9). Two other groups, infected untreated (group 10) and uninfected untreated (group 11), served as negative and positive control, respectively. The parameters assessed to determine the effective dose combination of the two were onset of parasitaemia (OP), level of parasitaemia (LOP), clearance of parasites post-treatment (COPPT), relapse of infection period (RIP), erythrocyte counts (EC), packed cell volume (PCV) and total leucocyte counts (TLC). There was no significant difference (p < 0.05) in OP between the groups. A day following treatment, the LOP of groups 1, 2, 3 and 4 was found to be significantly lower (p < 0.05) than that of groups 5 and 6 (p < 0.05) which in turn was lower (p < 0.05) than that of groups 7, 8 and 9, respectively. The mean COPPT of groups 5 and 6 was significantly (p < 0.05) longer than that of groups 1, 2, 3 and 4. There was no significant difference (p < 0.05) in the mean COPPT among groups 1, 2, 3 and 4. There was no clearance of parasites in groups 7, 8 and 9. The mean RIP of group 5 and 6 was significantly shorter (p < 0.05) than in group 4. There was no relapse of infection in group 1, 2 and 3 rats. Rats in groups 1, 2, 3 and 4 had significantly higher (p < 0.05) PCV, EC and TLC 10 days post-treatment, and that trend continued throughout the experimental period when compared to other infected groups. It was concluded that dose combination of 125 mg/kg bw extract plus 7 mg/kg bw DDA was the best dose combination judging from the parameters assessed.