Nerolidol nanospheres increases its trypanocidal efficacy against Trypanosoma evansi: New approach against diminazene aceturate resistance and toxicity

Baldissera, Matheus D.; Grando, Thirssa H.; Souza, Carine F.; Cossetin, Luciana F.; Sagrillo, Michele Rorato; Nascimento, Kátia; Silva, Ana P.T. da; Lana, Daiane Flores Dalla; Silva, Aleksandro S. Da; Stefani, Lenita M.; Monteiro, Sílvia González

doi:10.1016/j.exppara.2016.04.015

Cited by 26 publications

(14 citation statements)

References 39 publications

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“…Treatment of babesiosis remains a significant challenge, especially in the livestock industries. Although diminazene aceturate and imidocarb dipropionate are still effective, current reports showed the development of resistance in Trypanosoma evansi in cattle and a relapse of B. gibsoni in dogs ( Witola et al, 2005 ; Rajapakshage et al, 2012 ; Baldissera et al, 2016 ). Many inhibitors have been reported to be effective against in vitro or in vivo multiplication of Babesia and Theileria parasites; however, all of them are in research and still far from clinical trial ( Mosqueda et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

“…After decades of use, diminazene aceturate and imidocarb dipropionate are still the first choices for the treatment of animals ( Suarez and Noh, 2011 ; Oliveira and de Freitas, 2015 ). However, several problems such as the development of a resistant parasite, toxicity, drug residues, and withdrawal issues constrain the use of these drugs in many countries ( Kuttler, 1980 ; Coldham et al, 1995 ; Baldissera et al, 2016 ). Furthermore, they are not approved for human medicine.…”

Section: Introductionmentioning

confidence: 99%

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17-DMAG inhibits the multiplication of several Babesia species and Theileria equi on in vitro cultures, and Babesia microti in mice

Guswanto

Nugraha

Tuvshintulga

et al. 2018

International Journal for Parasitology: Drugs and Drug Resistan

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Heat shock protein 90 (Hsp90) is a chaperone protein that stabilizes cells during stress or non-stress responses. Previous reports have shown that Hsp90 is a potential drug target to suppress the multiplication of several protozoan parasites. In this study, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), an Hsp90 inhibitor, was evaluated for its inhibitory effect on five in vitro cultures of Babesia and Theileria species, including B. bovis, B. bigemina, B. divergens, B. caballi, and T. equi, and on the multiplication of a B. microti–infected mouse model. 17-DMAG showed the inhibitory effect in all of the species tested. The half maximum inhibition concentration (IC50) of 17-DMAG on B. bovis, B. bigemina, B. divergens, B. caballi, and T. equi was 77.6 ± 2.9, 62.4 ± 1.9, 183.8 ± 3.2, 88.5 ± 9.6, and 307.7 ± 7.2 nM, respectively. The toxicity assay on MDBK and NIH/3T3 cell lines showed that 17-DMAG affected the viability of cells with an IC50 of 15.5 ± 4 and 8.8 ± 2 μM, respectively. Since the IC50s were much lower on the parasites than on the host cell lines, the selectivity index were high for all tested species. Furthermore, the two-drug combination of 17-DMAG with diminazene aceturate (DA) and atovaquone (AV) showed synergism or addition on in vitro cultures of Babesia and Theileria parasites. In the mouse model, 17-DMAG at a concentration of 30 mg/kg BW effectively inhibited the multiplication of B. microti. Moreover, if combined with DA or AV, 17-DMAG showed a comparable inhibition at the half dose. Taken together, these results indicate that 17-DMAG is a potent drug for treating piroplamosis. The data warrant further evaluation of 17-DMAG as an antibabesial drug and as an option in combination with atovaquone for the treatment of human babesiosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

17-DMAG inhibits the multiplication of several Babesia species and Theileria equi on in vitro cultures, and Babesia microti in mice

Guswanto

Nugraha

Tuvshintulga

et al. 2018

International Journal for Parasitology: Drugs and Drug Resistan

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“…As a result, the disease can recur in treated animals. Moreover, restlessness, tissue injury at the site of injection, and abdominal pain were observed in animals after the DA treatment in addition to that it has not yet been approved for human use [32]. Therefore, a good combinatorial antibabesial drug is urgently needed.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effects of Atranorin towards the Proliferation of Babesia and Theileria Parasites

et al. 2020

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Atranorin (ATR), is a compound with multidirectional biological activity under different in vitro and in vivo conditions and it is effective as an antibacterial, antiviral, antiprotozoal and anti-inflammatory agent. In the current study, the in vitro as well as in vivo chemotherapeutic effect of ATR as well as its combined efficacy with the existing antibabesial drugs (diminazene aceturate (DA), atovaquone (AV) and clofazimine (CF)) were investigated on six species of piroplasm parasites. ATR suppressed B. bovis, B. bigemina, B. divergens, B. caballi and T. equi multiplication in vitro with IC50 values of 98.4 ± 4.2, 64.5 ± 3.9, 45.2 ± 5.9, 46.6 ± 2.5, and 71.3 ± 2.7 µM, respectively. The CCK test was used to examine ATR’s cytotoxicity and adverse effects on different animal and human cell lines, the main hosts of piroplasm parasites and it showed that ATR affected human foreskin fibroblasts (HFF), mouse embryonic fibroblast (NIH/3T3) and Madin-Darby Bovine Kidney (MDBK) cell viability in a dose-related effect with a moderate selective index. The combined efficacy of ATR with DA, CF, and AV exhibited a synergistic and additive efficacy toward all tested species. In the in vivo experiment, ATR prohibited B. microti multiplication in mice by 68.17%. The ATR-DA and ATR-AV combination chemotherapies were more potent than ATR monotherapy. These results indicate the prospects of ATR as a drug candidate for piroplasmosis treatment.

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“…As a result, the disease can recur in treated animals. Moreover, restlessness, tissue injury at the site of injection, and abdominal pain have been observed in animals after the treatment of DA [43]. Therefore, a good combinatorial babesicidal drug is urgently needed.…”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of hydroxyurea and eflornithine against most blood parasites Babesia and Theileria

et al. 2020

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Background The plenteous resistance to and undesirable consequences of the existing antipiroplasmic therapies have emphasized the urgent need for new chemotherapeutics and drug targets for both prophylaxis and chemotherapy. Hydroxyurea (HYD) is an antineoplastic agent with antitrypanosomal activity. Eflornithine (α-difluoro-methyl ornithine, DFMO) is the best choice therapy for the treatment of late-stage Gambian human African trypanosomiasis. Methods In this study, the inhibitory and combination efficacy of HYD and DFMO with existing babesicidal drugs (diminazene aceturate (DA), atovaquone (ATV), and clofazimine (CLF)) deoxyribonucleotide in vitro against the multiplication of Babesia and Theileria. As well as, their chemotherapeutic effects were assessed on B. microti strain that infects rodents. The Cell Counting Kits-8 (CCK-8) test was used to examine their cytotoxicity on human foreskin fibroblast (HFF), mouse embryonic fibroblast (NIH/3T3), and Madin-Darby bovine kidney (MDBK) cells. Findings HYD and DFMO suppressed the multiplication of all tested species (B. bigemina, B. bovis, B. caballi, B. divergens, and T. equi) in a dose-related manner. HFF, NIH/3T3, or MDBK cell viability was not influenced by DFMO at 1000 μM, while HYD affected the MDBK cell viability at EC 50 value of 887.5±14.4 μM. The in vitro combination treatments of DFMO and HYD with CLF, DA, and ATV exhibited synergistic and additive efficacy toward all tested species.

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Nerolidol nanospheres increases its trypanocidal efficacy against Trypanosoma evansi: New approach against diminazene aceturate resistance and toxicity

Cited by 26 publications

References 39 publications

17-DMAG inhibits the multiplication of several Babesia species and Theileria equi on in vitro cultures, and Babesia microti in mice

17-DMAG inhibits the multiplication of several Babesia species and Theileria equi on in vitro cultures, and Babesia microti in mice

Therapeutic Effects of Atranorin towards the Proliferation of Babesia and Theileria Parasites

Safety and efficacy of hydroxyurea and eflornithine against most blood parasites Babesia and Theileria

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