| 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 |
| Journal |
| 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 |
| Page |
|
| 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 |
| Author |
|
| Reviewing Status |
มีผู้ประเมินอิสระ |
| Status |
ได้รับการตอบรับให้ตีพิมพ์ |
| Level of Publication |
นานาชาติ |
| citation |
false |
| Part of thesis |
true |
| Attach file |
|
| Citation |
0
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Publication
Journal Publication
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