2012 ©
Journal Publication
Title of Article Repeated ivermectin treatment induces ivermectin resistance in Strongyloides ratti by upregulating the expression of ATP-binding cassette transporter genes 
Date of Acceptance 7 June 2021 
     Title of Journal American Society of Tropical Medicine and Hygiene  
     Standard SCOPUS 
     Institute of Journal American Society of Tropical Medicine and Hygiene  
     ISBN/ISSN 0002-9637 
     Volume 2021 
     Issue 104 
     Month JUNE
     Year of Publication 2021 
     Abstract Ivermectin (IVM) is a widely used anthelmintic. However, with widespread use comes the risk of the emergence of IVM resistance, particularly in strongyloidiasis. ATP-binding cassette transporter (ABC) genes play an important role in the IVM-resistance mechanism. Here, we aimed to establish an animal experimental model of IVM resistance by frequent treatment of Strongyloides ratti with sub-therapeutic doses of IVM, resistance being evaluated by expression levels of ATP-binding cassette transporter genes. Rats infected with S. ratti were placed in experimental groups as follows: 1) untreated control (control); 2) treated with the mutagen ethyl methanesulfonate (EMS); 3) injected with 100 μg/kg body weight of IVM (IVM); 4) treated with a combination of EMS and IVM (IVM+EMS). Parasites were evaluated after four generations. Extent of IVM resistance was assessed using IVM sensitivity, larval development and expression of ABC genes. By the F4 generation, S. ratti in the IVM group exhibited significantly higher levels of IVM resistance than did other groups according to in vitro drug-sensitivity tests and inhibition of larval development (IC50 = 36.60 ng/mL; 95% CI: 31.6, 42.01). Expression levels of ABC isoform genes (ABCA, ABCF and ABCG) were statistically significantly higher in the IVM-resistant line compared to the susceptible line. In conclusion, IVM sub-therapeutic doses induced IVM resistance in S. ratti by the F4 generation with corresponding upregulation of some ABC isoform genes. The study provides a model for inducing and assessing drug resistance in Strongyloides. 
     Keyword Strongyloides ratti, Ivermectin resistance, ATP binding cassette (ABC) transporters, rat 
587070009-2 Mr. CHATCHAWAN SENGTHONG [Main Author]
Medicine Doctoral Degree
Medicine Doctoral Degree
547100011-6 Mr. KITTI INTUYOD
Graduate School Doctoral Degree
587070027-0 Miss ORNUMA HAONON
Medicine Doctoral Degree
Graduate School Doctoral Degree

Reviewing Status มีผู้ประเมินอิสระ 
Status ได้รับการตอบรับให้ตีพิมพ์ 
Level of Publication นานาชาติ 
citation false 
Part of thesis true 
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