Evaluation of mebendazole activity on experimental murine toxocariasis by immune complexes determination.
The mebendazole action on experimental murine toxocariasis, using different formulations and vehicles, was studied by means of the detection of antibodies and immune complexes by ELISA. After inoculation with 1000 embryonated Toxocara canis eggs, BALB/c mice were submitted to the anthelmintic treatment as follows: group 1 (control without treatment); group 2 (mebendazole (MBZ), Lomper, Steve Laboratories, Barcelona, Spain, suspended in 1% sodium carboxymethylcellulose (CMC) at a dose of 100 mg/kg/day); group 3 (MBZ, pure compound suspended in 1% CMC at a dose of 100 mg/kg/day); group 4 (MBZ, pure compound suspended in water at a dose of 100 mg/kg/day); group 5 (MBZ, pure compound, formulated to a solid dispersion at 10% in polyethylene glycol 6000 (PEG) then dissolved in water at a dose of 100 mg/kg/day); group 6 (MBZ, pure compound, formulated to a solid dispersion at 10% in PEG then dissolved in water at a dose of 50 mg/kg/day); group 7 (MBZ, pure compound, formulated to a solid dispersion at 10% in PEG then dissolved in water at a dose of 25 mg/kg/day). The treatments were administered on days 5-7 post-inoculation (p.i.) inclusive. The dynamics of the production of the specific antibodies for both excretory-secretory (ES) antigen or crude extract showed a similar profile as compared to the control group. In groups 2 and 6, from the beginning of the treatment, values of immune complexes fell rapidly and were undetectable for the remainder of the experiment. Reductions of immune complex levels by the 4th-6th, 2nd-3rd and 2nd-5th weeks p.i. were observed from groups 3, 5 and 7, respectively. In the other groups, similar profiles as compared to the control group were observed in the dynamics of the specific immune complexes. The evaluation of chemotherapy by immunological methods is a valid technique for the efficiency of the treatment without the disadvantages of larval recovery from several digested tissues. Mebendazole, pure compound, formulated to a solid dispersion in PEG, then dissolved in water reduced immune complexes from the beginning of the treatment. The larval immobilization produced by MBZ should entail a reduction in their metabolic activity with a reduction in the production of excretory-secretory substances which are responsible for the formation of immune complexes. The rapid clearance of specific immune complexes together with a total larvae reduction would explain the decrease in specific immune complexes, which detection is a valid technique for monitoring the efficiency of treatment.
Bardon
R
R
Department of Parasitology, Faculty of Pharmacy, Complutense University of Madrid, Spain.
Cuellar
C
C
del Aguila
C
C
Guillen
J L
JL
D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood*; D000936:Antigen-Antibody Complex / Q000097:blood*; D000969:Antinematodal Agents / Q000627:therapeutic use*; D008463:Mebendazole / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D014119:Toxocara / Q000187:drug effects / Q000276:immunology*; D014120:Toxocariasis / Q000188:drug therapy* / Q000276:immunology
D000909:Antibodies, Helminth; D000936:Antigen-Antibody Complex; D000969:Antinematodal Agents; D008463:Mebendazole