The ABL kinase inhibitor imatinib causes phenotypic changes and lethality in adult Schistosoma japonicum

Parasitol Res. 2019 Mar;118(3):881-890. doi: 10.1007/s00436-019-06224-x. Epub 2019 Feb 7.

Abstract

Schistosomiasis caused by different species of schistosome parasites is one of the most debilitating helminthic diseases of humans worldwide. For decades, chemotherapy is the main method of controlling schistosomiasis. However, the fear of drug resistance has motivated the search for alternatives. It has been demonstrated that the ABL kinase inhibitor imatinib affected the development and survival of Schistosoma mansoni in vitro; however, there is still lack of information on whether imatinib also affects other schistosome species such as Schistosoma japonicum. In the present study, the anti-schistosomal potency of imatinib on adult S. japonicum was investigated in vitro, and the results showed that imatinib had a significant impact on various physiological processes of S. japonicum adult worms. Besides its negative effects on worm motility, pairing stability, and gonad development, imatinib caused pathological changes in the gastrodermis as well as the death of the parasite. Our findings suggest that imatinib is an intriguing candidate for further development as an option to fight S. japonicum.

Keywords: ABL kinases; Development; Imatinib; In vitro culture; Schistosoma japonicum.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Drug Resistance / genetics
  • Female
  • Gastropoda / parasitology
  • Humans
  • Imatinib Mesylate / therapeutic use*
  • Male
  • Mice
  • Parasitic Sensitivity Tests
  • Protein Kinase Inhibitors / therapeutic use*
  • Schistosoma japonicum / drug effects*
  • Schistosoma mansoni / drug effects
  • Schistosomiasis japonica / drug therapy*
  • Schistosomiasis japonica / parasitology
  • Schistosomicides / therapeutic use*
  • Sequence Alignment

Substances

  • Protein Kinase Inhibitors
  • Schistosomicides
  • Imatinib Mesylate