Anti-malarial effect of a combination of risedronate and azithromycin against Plasmodium yoelii nigeriensis infection in Swiss mice |
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| Institution: | 1. Institute of Pharmacy, Department of Pharmaceutical Biology, University of Greifswald, 17491 Greifswald, Germany;2. School of Pharmacy, College of Health Sciences, Addis Ababa University, Churchill Street, 1176 Addis Ababa, Ethiopia;3. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, 160062 Mohali, India;1. Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry and University Hospital, Palacky University Olomouc, Czech Republic;2. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden;3. A.V. Bogatsky Physico-Chemical Institute of National Academy of Sciences of Ukraine, Odessa, Ukraine;4. I.I. Mechnikova Odessa National University, Odessa, Ukraine;1. Department of Veterinary Parasitology, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar, Haryana 125004, India;2. Parasitology Lab, ICAR-National Research Centre on Equines, Hisar, Haryana 125001, India;3. Department of Veterinary Physiology and Biochemistry, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar, Haryana 125004, India;1. Biosecurity SA, Adelaide, SA 5001, Australia;2. School of Animal and Veterinary Sciences, The University of Adelaide, SA 5005, Australia;3. School of Agriculture, Food and Wine, The University of Adelaide, Adelaide, SA 5001, Australia;4. 22 Trevor Terrace Blackwood, SA 5051, Australia;5. Istituto Zooprofilattico Sperimentale della Lombardia e dell''Emilia Romagna and OIE Reference Laboratory for Rabbit Haemorrhagic Disease and for Myxomatosis, Via Bianchi 7/9, 25124 Brescia, Italy;6. Institute for Applied Ecology, University of Canberra, Bruce, ACT 2617, Australia;7. Australian National Wildlife Collection, National Research Collections CSIRO, Crace, ACT 2911, Australia;8. CSIRO Health & Biosecurity, Acton, ACT 2601, Australia;9. Invasive Species and Environment Biosecurity, Department of Primary Industries and Regional Development, Albany, WA 6330, Australia;10. Biosecurity Tasmania, Newtown, Tasmania 7008, Australia;11. NSW Department of Primary Industries, Orange, NSW 2800, Australia;12. Centre for Invasive Species Solutions, Bruce, ACT 2617, Australia;1. Cell and Molecular Biology Laboratory, Department of Zoology, Soban Singh Jeena University, Campus Almora, Uttarakhand, India;2. Department of Zoology, Kumaun University, Nainital, Uttarakhand, India;1. Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510542, China;2. Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt |
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| Abstract: | Combination therapy is used to retard the selection of malaria parasite strains resistant to individual components of a combination of drugs. This approach has proved to be a success in the combination of sulphadoxine and pyrimethamine, which targets two different steps in the folate pathway of malaria parasites. However, after the success of this therapeutic combination, the efficacy of other combinations of drugs that target different enzymes in a particular metabolic pathway has, apparently, not been reported. In the current study, the antimalarial effect of a combination of risedronate (RIS), which is known for its anti-osteoporosis activity, and azithromycin (AZT) was investigated. Peter's suppression test was carried out on mice infected with 1 × 107 P. yoelii infected erythrocytes. Drug efficacy was analyzed by comparing the percent reduction in parasitaemia on day 4 post-infection. RIS was observed to be a blood schizonticidal agent against P. yoelii infection which showed ED50 7.0 (4.04–12.13) mg/kg/day x 4. Normalized isobologram showed additive action between RIS 1 mg/kg/day x 4 and AZT 10 mg/kg/day x 4, and antagonistic action for the rest of the combinations (RIS 1 + AZT 20, RIS 1 + AZT 40, RIS 5 + AZT 10, RIS 5 + AZT 20, RIS 5 + AZT 40, RIS 10 + AZT 10, RIS 10 + AZT 20 and RIS 10 + AZT 40 mg/kg/day x 4). Furthermore, a combination of RIS with AZT showed inferior efficacy as compared to AZT treatment alone. This antagonistic interaction may be due to the high accumulation of AZT in WBCs, which will reduce its serum bio-availability, whereas RIS has anti-parasitic activity by increasing WBCs. |
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