La anfotericina B normalmente es subdosificada en el tratamiento de la leishmaniasis cutánea experimental

  1. Sergio Sifontes Rodríguez
  2. Claudia Sissely Chaviano-Montes de Oca
  3. Lianet Monzote-Fidalgo
  4. Susana Meneses-Gómez
  5. Niurka Mollineda-Diogo
  6. José Antonio Escario García-Trevijano
Journal:
Ars pharmaceutica

ISSN: 2340-9894,  0004-2927

Year of publication: 2022

Volume: 63

Issue: 3

Pages: 253-262

Type: Article

DOI: 10.30827/ARS.V63I3.23894 DIALNET GOOGLE SCHOLAR lock_openOpen access editor

More publications in: Ars pharmaceutica

Abstract

Introduction: Amphotericin B is an effective drug for the treatment of the different clinical forms of leishmaniasis. However, there are reports of its ineffectiveness in animals experimentally infected with Leishmania spp. That is why, the objective of the present work was to evaluate the balance of activity-toxicity at amphotericin B doses over 1 mg/kg, so that its use as a positive control antileishmanial drug were adequate. Method: BALB/c mice were experimentally infected with L. amazonensis and treated with amphotericin B by intraperitoneal route at doses from 5 mg/kg to 12.5 mg/kg, beginning 21 days after infection. The size of the lesions and the body weight of the mice were measured for eleven weeks after the commencement of treatment. The number of parasites was also determined three days after the end of treatment. Results: Amphotericin B at 5 mg/kg retarded lesions growth but neither reduced lesion size nor the parasite load at lesion site. Doses of 7.5 mg/kg to 10 mg/kg, every 48 h for 14 days (7 doses) caused a significant reduction of lesion size and parasite load without evident loss of body weight and without signs of toxicity. Amphotericin B at 12.5 mg/kg was more effective but produced unacceptable toxicity. Conclusions: The results support the use of amphotericin B as a positive control drug in BALB/c mice experimentally infected with L. amazonensis at doses of 7.5 mg/kg to 10 mg/kg to achieve an effect comparable to that observed in clinical practice.

Bibliographic References

  • Stephens N, Rawlings B, Caffrey P. Streptomyces nodosus Host Strains Optimized for Polyene Glycosylation Engineering. Biosci Biotechnol Biochem. 2012;76(2):384–7. doi: 10.1271/bbb.110673.
  • Shirzadi, MR. Liposomal amphotericin B: a review of its properties, function, and use for treatment of cutaneous leishmaniasis. Res Rep Trop Med. 2019;10:11-8. doi: 10.2147/RRTM.S200218
  • Sabra R, Branch RA. Amphotericin B nephrotoxicity. Drug Saf. 1990;5(2):94-108. doi: 10.2165/00002018-199005020-00003.
  • Bekersky I, Boswell GW, Hiles R, Fielding RM, Buell D, Walsh TJ. Safety, toxicokinetics and tissue distribution of long-term intravenous liposomal amphotericin B (AmBisome®): a 91-day study in rats. Pharm Res. 2000;17(12):1494–502. doi:10.1023/A:1007605024942.
  • Santos CR, Tuon FF, Cieslinski J, de Souza RM, Imamura R, Amato VS. Comparative study on liposomal amphotericin B and other therapies in the treatment of mucosal leishmaniasis: A 15-year retrospective cohort study. PLoS One. 2019 Jun 26;14(6):e0218786. doi: 10.1371/journal.pone.0218786.
  • Sundar S, Singh, A. Chemotherapeutics of visceral leishmaniasis: present and future developments. Parasitol. 2018;145(4):481-9. doi:10.1017/S0031182017002116
  • Mistro S, Rodrigues M, Rosa L, Camargo M, Badaro R. Liposomal Amphotericin B drug access for the treatment of leishmaniasis in Brazil. Trop Med Int Health. 2016;21(6): 692-3. doi:10.1111/tmi.12697
  • Ghorbani M, Farhoudi R. Leishmaniasis in humans: drug or vaccine therapy? Drug Des Devel Ther. 2018;12:25-40. doi: 10.2147/DDDT.S146521.
  • Rocha V, Quintino C, Ferreira E et al. Antileishmanial Activity of Dimeric Flavonoids Isolated from Arrabidaea brachypoda. Molecules. 2019;24(1):1-13. doi: 10.3390/molecules24010001.
  • Van Bocxlaer K, Caridha D, Black C et al. Novel benzoxaborole, nitroimidazole and aminopyrazoles with activity against experimental cutaneous leishmaniasis. Int J Parasitol Drugs Drug Resist 2019; 11:129-38. doi: 10.1016/j.ijpddr.2019.02.002.
  • Trinconi C, Reimão J, Yokoyama-Yasunaka J, Miguel D, Uliana S. Combination Therapy with Tamoxifen and Amphotericin B in Experimental Cutaneous Leishmaniasis. Antimicrob Agents Chemother. 2014;58(5):2608-13. doi:10.1128/AAC.01315-13.
  • Sifontes-Rodríguez S, Monzote-Fidalgo L, Castañedo-Cancio N et al. The efficacy of 2-nitrovinylfuran derivatives against Leishmania in vitro and in vivo. Mem Inst Oswaldo Cruz. 2015;110(2):166-73. doi: 10.1590/0074-02760140324
  • Monzote L, Piñón A, Scull R, Setzer W. Chemistry and Leishmanicidal Activity of the Essential Oil from Artemisia absinthium from Cuba. Nat Prod Commun. 2014;9(12):1799-804.
  • Casa D, Scariot D, Khalil N, Nakamura C, Mainardes R. Bovine serum albumin nanoparticles containing amphotericin B were effective in treating murine cutaneous leishmaniasis and reduced the drug toxicity. Exp Parasitol. 2018;192:12-8. doi:10.1016/j.exppara.2018.07.003.
  • Reimão J, Trinconi C, Yokoyama-Yasunaka J, Miguel D, Kalil S, Uliana S. Parasite burden in Leishmania (Leishmania) amazonensis-infected mice: Validation of luciferase as a quantitative tool. J Microbiol Methods. 2013;93(2):95–101. doi:10.1016/j.mimet.2013.02.007.
  • Varikuti S, Oghumu S, Saljoughian N et al. Topical treatment with nanoliposomal Amphotericin B reduces early lesion growth but fails to induce cure in an experimental model of cutaneous leishmaniasis caused by Leishmania mexicana. Acta Trop. 2017;173:102–8. doi: 10.1016/j.actatropica.2017.06.004.
  • Nguyen A, Yang K, Bryant K et al. Microneedle-Based Delivery of Amphotericin B for Treatment of Cutaneous Leishmaniasis. Biomed Microdevices. 2019;21(8):1-10. doi: 10.1007/s10544-018-0355-8.
  • Committee for the Update of the Guide for the Care and Use of Laboratory Animals, Institute for Laboratory Animal Research. Guide for the care and use of laboratory animals. Eighth edition. The National Academies Press, Washington DC, 2011, 246 p.
  • NIH Office of Animal Care and Use. Animal Research Advisory Committee Guidelines: Guidelines for Endpoints in Animal Study Proposals. Approved by ARAC 10/09/96, Reapproved - 02/10/99, Last revision 04/24/19. Accessed 04/14/2022. https://oacu.oir.nih.gov/system/files/media/file/2021-02/b13_endpoints_guidelines.pdf
  • Titus RG, Marchand M, Boon T, Louis JA. A limiting dilution assay for quantifying Leishmania major in tissues of infected mice. Paras Immunol. 1985;7(5): 545-55. doi: 10.1111/j.1365-3024.1985.tb00098.x
  • OECD, Test No. 423: Acute Oral toxicity - Acute Toxic Class Method, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris; 2002, 14 p. doi: 10.1787/9789264071001-en.
  • Rugani J, Quaresma P, Gontijo C, Soares R, Monte-Neto R. Intraspecies susceptibility of Leishmania (Viannia) braziliensis to antileishmanial drugs: Antimony resistance in human isolates from atypical lesions. Biomed Pharmacother. 2018;108:1170–80. doi: 10.1016/j.biopha.2018.09.149.
  • Basile G, Cristofaro G, Locatello L et al. Refractory mucocutaneous leishmaniasis resolved with combination treatment based on intravenous pentamidine, oral azole, aerosolized liposomal amphotericin B and intralesional meglumine antimoniate. Int J Infect Dis. 2020;97:204-7. doi: 10.1016/j.ijid.2020.06.003.
  • Ayres D, Fedele T, Marcucci M, Giorgio S. Potential utility of hiperbaric oxygen therapy and propolis in enhancing the leishmanicidal activity of glucantime. Rev Inst Med Trop Sao Paulo. 2011;53(6):329-34. doi: 10.1590/s0036-46652011000600006.
  • Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J 2008;22(3):659-61. doi: 10.1096/fj.07-9574LSF
  • Serrano-Martín X, Payares G, De Lucca M, Martinez J, Mendoza-León A, Benaim G. Amiodarone and miltefosine act synergistically against Leishmania mexicana and can induce parasitological cure in a murine model of cutaneous leishmaniasis. Antimicrob Agents Chemother. 2009;53(12):5108-13. doi: 10.1128/AAC.00505-09.
  • Souza-Silva F, Cabral-Bourguignon S, Acácio B et al. Epoxy-α-lapachone has in vitro and in vivo anti-leishmania (Leishmania) amazonensis effects and inhibits serine proteinase activity in this parasite. Antimicrob Agents Chemother. 2015;59(4):1910-18. doi: 10.1128/AAC.04742-14.
  • Coutinho S, Pirmez C, Da-Cruz A. Parasitological and immunological follow-up of American tegumentary leishmaniasis patients. Trans R Soc Trop Med Hyg. 2002;96(1):173-8. doi: 10.1016/s0035-9203(02)90072-6.
  • Gabriel A, Valério-Bolas A, Palma-Marques J et al. Cutaneous Leishmaniasis: The Complexity of Host’s Effective Immune Response against a Polymorphic Parasitic Disease. J Immunol Res. 2019;(2603730). doi: 10.1155/2019/2603730.
Data source: Dialnet