Synergistic effect calcium channel blockers and praziquantel treatment in murine schistosomiasis

ABSTRACT

This work was conducted to study the potential drug interaction between calcium channel blockers [CCBs], commonly used as antihypertensives, and the antihelminthic agent praziquantel [PZQ] in Schistosoma mansoni infected mice. Two CCBs namely nifedipine and diltiazem were used either alone or in combination with PZQ, in full or reduced doses [500 mg/kg/day for 2 successive days or 250 mg/kg/day]. The experimental design included eight groups; infected-nifedipine treated [300 mg/kg for 3 weeks [wks]]; infected-nifedipine-PZQ treated; infected-diltiazem treated [300 mg/kg for 3 wks]; infected-diltiazem-PZQ treated; infected control and infected-PZQ treated. Eight wks postinfection [Pt] animals of all groups were sacrificed for subsequent parasitological, immunological and histopathological assessment. Data collected in this work revealed that treatment with nifedipine or diltiazem significantly reduced the egg production by adult schistosome worm as manifested by reduction in tissue egg load and decreased percent of immature ova in oogram pattern. This reduction was more in favor with nifedipine. The groups given the combined regimens of CCBs [nifedipine or diltiazem] and PZQ either in reduced [250 mg/kg/day] or full [500 mg/kg/ day] doses, showed more significant reduction in egg production in addition to high significant reduction in worm burden, as compared to infected control group. The number of granukima also decreased significantly in all treated groups; this could be due o decrease in egg production. The antischistosomal IgG level was increased significantly in PZQ-treated group and groups receiving combined regimens of CCBs and PZQ with different doses; while no significant change in the IgM levels was recorded among different studied groups. In conclusion administration of CCBs in the early phase of infection would inhibit egg production by parasitic worms, thus probably acting in synergy with PZQ and not interfering with its action. Further studies are needed to evaluate the possible use of lower doses of PZQ in combination with CCBs. The reported data of this work may be of value in endemic areas where schistosome infected patients could be suffering from other chronic diseases necessitating treatment with CCBs, as hypertension