The effect of ivermectin alone and in combination with cobicistat or elacridar in experimental Schistosoma mansoni infection in mice
Abstract Schistosoma mansoni is less susceptible to the antiparasitic drug ivermectin than other helminths. By inhibiting the P-glycoprotein or cytochrome P450 3A in mice host or parasites in a murine model, we aimed at increasing the sensitivity of S. mansoni to the drug and thus preventing infecti...
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Nature Portfolio
2021
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oai:doaj.org-article:009dfc25093b418f859d617fa63c71552021-12-02T15:53:46ZThe effect of ivermectin alone and in combination with cobicistat or elacridar in experimental Schistosoma mansoni infection in mice10.1038/s41598-021-84009-y2045-2322https://doaj.org/article/009dfc25093b418f859d617fa63c71552021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84009-yhttps://doaj.org/toc/2045-2322Abstract Schistosoma mansoni is less susceptible to the antiparasitic drug ivermectin than other helminths. By inhibiting the P-glycoprotein or cytochrome P450 3A in mice host or parasites in a murine model, we aimed at increasing the sensitivity of S. mansoni to the drug and thus preventing infection. We assigned 124 BALB/c mice to no treatment, treatment with ivermectin only or a combination of ivermectin with either cobicistat or elacridar once daily for three days before infecting them with 150 S. mansoni cercariae each. The assignment was done by batches without an explicit randomization code. Toxicity was monitored. At eight weeks post-infection, mice were euthanized. We determined number of eggs in intestine and liver, adult worms in portal and mesenteric veins. Disease was assessed by counting granulomas/cm2 of liver and studying organ weight indices and total weight. IgG levels in serum were also considered. No difference between groups treated with ivermectin only or in combination with cobicistat or elacridar compared with untreated, infected controls. Most mice treated with ivermectin and elacridar suffered severe neurological toxicity. In conclusion, systemic treatment with ivermectin, even in the presence of pharmacological inhibition of P-glycoprotein or cytochrome P450 3A, did not result in effective prophylaxis for S. mansoni infection in an experimental murine model.Belén VicenteJulio López-AbánJuliane ChaccourJuan Hernández-GoenagaPatricia NicolasPedro Fernández-SotoAntonio MuroCarlos ChaccourNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021) |
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Medicine R Science Q Belén Vicente Julio López-Abán Juliane Chaccour Juan Hernández-Goenaga Patricia Nicolas Pedro Fernández-Soto Antonio Muro Carlos Chaccour The effect of ivermectin alone and in combination with cobicistat or elacridar in experimental Schistosoma mansoni infection in mice |
| description |
Abstract Schistosoma mansoni is less susceptible to the antiparasitic drug ivermectin than other helminths. By inhibiting the P-glycoprotein or cytochrome P450 3A in mice host or parasites in a murine model, we aimed at increasing the sensitivity of S. mansoni to the drug and thus preventing infection. We assigned 124 BALB/c mice to no treatment, treatment with ivermectin only or a combination of ivermectin with either cobicistat or elacridar once daily for three days before infecting them with 150 S. mansoni cercariae each. The assignment was done by batches without an explicit randomization code. Toxicity was monitored. At eight weeks post-infection, mice were euthanized. We determined number of eggs in intestine and liver, adult worms in portal and mesenteric veins. Disease was assessed by counting granulomas/cm2 of liver and studying organ weight indices and total weight. IgG levels in serum were also considered. No difference between groups treated with ivermectin only or in combination with cobicistat or elacridar compared with untreated, infected controls. Most mice treated with ivermectin and elacridar suffered severe neurological toxicity. In conclusion, systemic treatment with ivermectin, even in the presence of pharmacological inhibition of P-glycoprotein or cytochrome P450 3A, did not result in effective prophylaxis for S. mansoni infection in an experimental murine model. |
| format |
article |
| author |
Belén Vicente Julio López-Abán Juliane Chaccour Juan Hernández-Goenaga Patricia Nicolas Pedro Fernández-Soto Antonio Muro Carlos Chaccour |
| author_facet |
Belén Vicente Julio López-Abán Juliane Chaccour Juan Hernández-Goenaga Patricia Nicolas Pedro Fernández-Soto Antonio Muro Carlos Chaccour |
| author_sort |
Belén Vicente |
| title |
The effect of ivermectin alone and in combination with cobicistat or elacridar in experimental Schistosoma mansoni infection in mice |
| title_short |
The effect of ivermectin alone and in combination with cobicistat or elacridar in experimental Schistosoma mansoni infection in mice |
| title_full |
The effect of ivermectin alone and in combination with cobicistat or elacridar in experimental Schistosoma mansoni infection in mice |
| title_fullStr |
The effect of ivermectin alone and in combination with cobicistat or elacridar in experimental Schistosoma mansoni infection in mice |
| title_full_unstemmed |
The effect of ivermectin alone and in combination with cobicistat or elacridar in experimental Schistosoma mansoni infection in mice |
| title_sort |
effect of ivermectin alone and in combination with cobicistat or elacridar in experimental schistosoma mansoni infection in mice |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/009dfc25093b418f859d617fa63c7155 |
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