Effects of toltrazuril and ponazuril on the fine structure and multiplication of tachyzoites of the NC-1 strain of Neospora caninum (a synonym of Hammondia heydorni) in cell cultures

Abstract

Rhesus monkey kidney cell cultures were used to propagate tachyzoites of the NC-1 strain of Neospora caninum (syn. Hammondia heydorni). The infected cell cultures were incubated for 4-12 h in media containing 0, 1, 10 or 100 microg/ml of either toltrazuril or ponazuril. The effects were studied by light and electron microscopy. Drug dosages of at least 30 microg/ml were needed to eliminate the parasites. Ponazuril was found (with respect to the reduction of the number of parasites) to be less effective at dosages of 30 microg/ml compared to toltrazuril. However, the damage to the tachyzoites being incubated in 30 microg toltrazuril or ponazuril seen by electron microscopy was so significant that it was surely lethal. The initial damage occurred within the apicoplast and the tubular mitochondrion in all cases,thus destroying two of the most important cell organelles.