Microtubules are damaged by diethylcarbamazine, anti-filarial drug

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Mak et al. (1983) recently reported an culture system that allows the infective larvae of Brugia pahangi to develop to the fourth stage. Our preliminary study by using the technique of Mak suggested that diethylcarbamazine (DEC) does not kill the larvae of B. pahangi in vitro, even at a high concentration (1 mg/ml), but it inhibits the growth and development of larvae. This results encouraged us to examine the effect of DEC on the feeder cells and filarial larvae.Firstly the effect of DEC on the feeder cells was studied. The cells used in our study were LLC-MK_2 cells. DEC inhibited proliferation of these cells, and cells grown in the presence of DEC were likely to separate from each other and became round in shape. These results encouraged us to study the cytoplasmic microtubules complex. Immunofluorescence microscopy revealed that the cells exposed to DEC were devoid of the delicate pattern of the cytoplasmic microtubules complex. Subsequently, the effect of DEC on microtubules was s … More tudied by using microtubule protein prepared from porcine brain. DEC inhibited assembly of microtubules and disassembled preformed microtubules in vitro. When the reassembled or disassembled products were examined in the presence of DEC by electron microscopy; ribbon-microtubules were frequently observed. These results strongly suggest that DEC disrupts the function of the feeder cells which support the development of filarial larvae in vitro.Secondly, a preliminary study was designed to know the effect of DEC on filasial microtubules. The infective larvae were pre-incubated with DEC in vitro in the absence of feede cells and then inoculated into jirds. The animals were necropsied at a given intervals and the larvae recovered were examined for development. The larvae exposed to DEC did not survive long, nor develop. As we know that DEC has direct effect on larvae in vitro, the problem to be solved is whether DEC gives any damage on amphids, phasmids and excretory cells, the specific organs which are rich in microtubules among the organs and tissues of filarial worms. Less