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Published on: October 18, 2017
Albendazole induces apoptosis in adults and microfilariae of Setaria cervi
1Parasitology Laboratory, Department of Zoology, Visva-Bharati University, Santiniketan, West Bengal 731 235, India.
Abstract:
Setaria cervi, a filarial nematode of cattle, inhabits in the peritoneal cavity and has been used as a suitable model for screening antifilarial agents. Albendazole (ABZ), a tubulin-disrupting benzimidazole (BZ) and a potent microfilaricide binds to β-tubulin, is causing structural impairment of cytoskeleton and worm death. Our present study has revealed that exposure of microfilaria (Mf) and adult to gradually increasing concentration of ABZ leads to a dose-dependent gradual impairment of their motility followed by early death in vitro. We found extreme cellular disturbances in ABZ-treated worms characterized by nucleosomal DNA laddering and chromatin condensation. However, in the treated Mf no nucleosomal DNA laddering was found although presence of TUNEL reactive DNA was evident, thus indicating an apoptotic pathway independent of DNA fragmentation. We present data from molecular studies to provide evidence for ABZ-induced apoptosis in Mf and adult worms of S. cervi.
Insights
Albendazole (ABZ) induces apoptosis in the cattle filarial worm, Setaria cervi. This antifilarial agent causes dose-dependent impairment and death in microfilaria and adult worms by disrupting cellular structures.
Area of Science:
- Veterinary Parasitology
- Molecular Biology
- Drug Discovery
Background:
- Setaria cervi, a cattle filarial nematode, is a model for antifilarial drug screening.
- Albendazole (ABZ), a benzimidazole, targets β-tubulin, disrupting the cytoskeleton and causing worm death.
Purpose of the Study:
- To investigate the cellular and molecular mechanisms of Albendazole-induced death in Setaria cervi.
- To provide evidence for ABZ-induced apoptosis in both microfilaria (Mf) and adult S. cervi.
Main Methods:
- In vitro exposure of S. cervi microfilaria and adults to increasing concentrations of Albendazole.
- Assessment of worm motility and viability.
- Analysis of cellular disturbances including DNA laddering and chromatin condensation.
- TUNEL assay to detect DNA fragmentation.
- Molecular studies to confirm apoptosis.
Main Results:
- Albendazole exposure caused dose-dependent impairment of motility and premature death in S. cervi.
- Cellular disturbances observed included nucleosomal DNA laddering and chromatin condensation in adult worms.
- Microfilaria showed TUNEL-reactive DNA, indicating apoptosis independent of nucleosomal DNA fragmentation.
- Molecular data confirmed ABZ-induced apoptosis in both life stages.
Conclusions:
- Albendazole induces apoptosis in Setaria cervi microfilaria and adult worms.
- The antifilarial mechanism involves dose-dependent cellular disruption and apoptosis, potentially via distinct pathways in different life stages.
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