Effects of Three Anthelmintics on the Transcriptome of FHs 74 Int Enterocytes

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Helminth infections continue to present a substantial public health challenge worldwide, particularly in tropical and developing areas. Despite the widespread use of anthelmintic drugs for treatment and control, their effects on host cells remain poorly understood. In this study, the three commonly used anthelmintics albendazole, ivermectin, and praziquantel were investigated by transcriptome analysis for their effects on gene activity in the human intestinal cell line FHs 74 Int after 24-h exposure. The drug concentrations used were substantially higher than in the treatment of helminthiases but did not affect cell viability after 24 h and less than 50% after 72 h. Praziquantel had negligible toxic effects on the intestinal cells at the highest achievable concentration of 1 mM whereas albendazole and ivermectin were already effective at low micromolar concentrations and were tested at 1 µM and 15 µM concentrations. Consistent with the observed cytotoxicity, transcriptome analysis showed no transcriptional changes for 1 mM praziquantel at low cutoff criteria of adjusted p-value (padj) ≤ 0.05, log2 fold change ≥ 0. At the same padj but with log2 fold change ≥ 2, 17 upregulated and 2 downregulated genes were found after treatment with 1 µM albendazole and 106 upregulated and 65 downregulated genes with 15 µM ivermectin. Analysis of these genes showed that albendazole caused a modest upregulation of cell cycle related processes, especially mitotic spindle formation, and chromosome segregation. The cells showed a stronger response to ivermectin and the data suggested inhibition of cell proliferation through downregulated transcription factors and nuclear receptors and stimulation of cell growth and cell survival mechanisms through upregulated metabolic enzymes.

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