The Effect of Iodium 30c on Experimental Visceral LeishmaniasisFunding Author L.M.Y. is supported by the NICHD K12 HD050121–11. Research reported in this publication was supported, in part, by the National Institutes of Health's National Center for Advancing Translational Sciences, Grant Number UL1TR001422. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Background Leishmaniasis is one of several neglected tropical diseases that warrant serious attention. A disease of socio-economically poor people, it demands safer and cheaper drugs that help to overcome the limitations faced by the existing anti-leishmanials. Complementary or traditional medicines might be a good option, with an added advantage that resistance may not develop against these drugs. Thus, the present investigation was performed to evaluate the anti-leishmanial efficacy of an ultra-diluted homeopathic medicine (Iodium 30c) in experimental visceral leishmaniasis (VL).
Methods Compliant with strict ethical standards in animal experimentation, the study was performed in-vivo in inbred BALB/c mice which were injected intravenously with 1 × 107 promastigotes of Leishmania donovani before (therapeutic) or after (prophylactic) treatment with Iodium 30c for 30 days. In other groups of mice (n = 6 per group), amphotericin B served as positive control, infected animals as the disease control, while the naïve controls included normal animals; animals receiving only Iodium 30c or Alcohol 30c served as sham controls. The anti-leishmanial efficacy was assessed by determining the hepatic parasite load and analysing percentages of CD4+ and CD8+ T cells. Biochemical analysis and histological studies were performed to check any toxicities.
Results Iodium-treated animals showed a significantly reduced parasite load (to 1503 ± 39 Leishman Donovan Units, LDU) as compared with the infected controls (4489 ± 256 LDU) (p < 0.05): thus, the mean therapeutic efficacy of Iodium 30c was 66.5%. In addition, the population of CD4+ and CD8+ T cells was significantly increased (p < 0.05) after treatment. No toxicity was observed, as evidenced from biochemical and histopathological studies of the liver and kidneys. Efficacy of Iodium 30c prophylaxis was 58.3%, while the therapeutic efficacy of amphotericin B was 85.9%.
Conclusion This original study has shown that Iodium 30c had significant impact in controlling parasite replication in experimental VL, though the effect was less than that using standard pharmaceutical treatment.
• The anti-parasitic efficacy of the homeopathic medicine Iodium 30c was evaluated in experimental VL.
• Iodium 30c treatment reduced the parasite load, with a therapeutic efficacy of 66.5%.
• The effect was less than that using the anti-leishmanial drug amphotericin B.
• Iodium 30c did not cause any hepatic or renal damage.
Received: 03 December 2019
Accepted: 11 April 2020
21 August 2020 (online)
© 2020. Thieme. All rights reserved.
The Faculty of Homeopathy
- 1 Alcântara LM, Ferreira TCS, Gadelha FR, Miguel DC. Challenges in drug discovery targeting TriTryp diseases with an emphasis on leishmaniasis. Int J Parasitol Drugs Drug Resist 2018; 8: 430-439
- 2 World Health Organization. Leishmaniasis. Available at: https://www.who.int/leishmaniasis/en/ . Accessed June 9, 2019
- 3 Sundar S, Singh OP, Chakravarty J. Visceral leishmaniasis elimination targets in India, strategies for preventing resurgence. Expert Rev Anti Infect Ther 2018; 16: 805-812
- 4 Contreras MEM. Chemotherapy used in the treatment of visceral leishmaniasis. CPQ Microbiol 2019; 3: 1-14
- 5 Thakur L, Singh KK, Shanker V. et al. Atypical leishmaniasis: a global perspective with emphasis on the Indian subcontinent. PLoS Negl Trop Dis 2018; 12: e0006659
- 6 Jain K, Jain NK. Novel therapeutic strategies for treatment of visceral leishmaniasis. Drug Discov Today 2013; 18: 1272-1281
- 7 Sundar S. Drug resistance in Indian visceral leishmaniasis. Trop Med Int Health 2001; 6: 849-854
- 8 Prajapati VK, Awasthi K, Gautam S. et al. Targeted killing of Leishmania donovani in-vivo and in-vitro with amphotericin B attached to functionalized carbon nanotubes. J Antimicrob Chemother 2011; 66: 874-879
- 9 Prajapati VK, Awasthi K, Yadav TP, Rai M, Srivastava ON, Sundar S. An oral formulation of amphotericin B attached to functionalized carbon nanotubes is an effective treatment for experimental visceral leishmaniasis. J Infect Dis 2012; 205: 333-336
- 10 Wiwanitkit V. Interest in paromomycin for the treatment of visceral leishmaniasis (kala-azar). Ther Clin Risk Manag 2012; 8: 323-328
- 11 Mondal D, Alvar J, Hasnain MG. et al. Efficacy and safety of single-dose liposomal amphotericin B for visceral leishmaniasis in a rural public hospital in Bangladesh: a feasibility study. Lancet Glob Health 2014; 2: e51-e57
- 12 Sundar S, Mehta H, Suresh AV, Singh SP, Rai M, Murray HW. Amphotericin B treatment for Indian visceral leishmaniasis: conventional versus lipid formulations. Clin Infect Dis 2004; 38: 377-383
- 13 Gervazoni LFO, Gonçalves-Ozório G, Almeida-Amaral EE. 2′-Hydroxyflavanone activity in-vitro and in-vivo against wild-type and antimony-resistant Leishmania amazonensis . PLoS Negl Trop Dis 2018; 12: e0006930
- 14 Berman J, Bryceson AD, Croft S. et al. Miltefosine: issues to be addressed in the future. Trans R Soc Trop Med Hyg 2006; 100 (Suppl. 01) S41-S44
- 15 World Health Organization (WHO). WHO Traditional medicine strategy: 2014–2023. 2013: 1-78 . Available at: https://www.who.int/medicines/publications/traditional/trm_strategy14_23/en/
- 16 Rodrigues de Santana F, Coelho CdeP, Cardoso TN, Laurenti MD, Perez Hurtado EC, Bonamin LV. Modulation of inflammation response to murine cutaneous Leishmaniosis by homeopathic medicines: thymulin 5cH. Homeopathy 2014; 103: 275-284
- 17 Lira-Salazar G, Marines-Montiel E, Torres-Monzón J, Hernández-Hernández F, Salas-Benito JS. Effects of homeopathic medications Eupatorium perfoliatum and Arsenicum album on parasitemia of Plasmodium berghei-infected mice. Homeopathy 2006; 95: 223-228
- 18 Pereira WKV, Lonardoni MVC, Grespan R, Caparroz-Assef SM, Cuman RKN, Bersani-Amado CA. Immunomodulatory effect of Canova medication on experimental Leishmania amazonensis infection. J Infect 2005; 51: 157-164
- 19 Lachapelle J-M, Castel O, Casado AF. et al. Antiseptics in the era of bacterial resistance: a focus on povidone iodine. Clin Pract 2013; 10: 579-592
- 20 Government of India. Homoeopathic Pharmacopoeia of India. 1971 . Available at: https://pcimh.gov.in/show_content.php?lang=1&level=1&ls_id=59&lid=57
- 21 Boericke W. In: Oscar E, Boericke AB. , eds. Pocket Manual of Homeopathic Materia Medica. 9th ed. San Francisco: Boericke & Tafel; 1927: 349-351
- 22 Bradley DJ, Kirkley J. Regulation of Leishmania populations within the host. I. the variable course of Leishmania donovani infections in mice. Clin Exp Immunol 1977; 30: 119-129
- 23 Kaur G, Chauhan K, Kaur S. Immunotherapeutic potential of Codonopsis clematidea and naringenin against visceral leishmaniasis. Biomed Pharmacother 2018; 108: 1048-1061
- 24 Handman E, Ceredig R, Mitchell GF. Murine cutaneous leishmaniasis: disease patterns in intact and nude mice of various genotypes and examination of some differences between normal and infected macrophages. Aust J Exp Biol Med Sci 1979; 57: 9-29
- 25 Howard JG, Hale C, Chan-Liew WL. Immunological regulation of experimental cutaneous leishmaniasis. 1. Immunogenetic aspects of susceptibility to Leishmania tropica in mice. Parasite Immunol 1980; 2: 303-314
- 26 Handman E. Leishmaniasis: current status of vaccine development. Clin Microbiol Rev 2001; 14: 229-243
- 27 Silva LM, Silvio Verçosa BLA, Moreira HM. et al. Survival in golden Syrian hamster (Mesocricetus auratus) infected by Leishmania chagasi changes according to gender and homeopathic product – factors of self-organization. Int J High Dilution Res 2013; 12: 112-113
- 28 Cardoso TN, Amaral J, Carvalho AC. et al. Carbo animalis and immune response to Ehrlich ascites tumor in mice: an experimental model. Homeopathy 2016; 105: 10-11
- 29 Rodrigues de Santana F, de Paula Coelho C, Cardoso TN. et al. Modulation of inflammation response to murine cutaneous Leishmaniasis by homeopathic medicines: antimonium crudum 30cH. Homeopathy 2014; 103: 264-274
- 30 de Santana FR, Dalboni LC, Nascimento KF. et al. High dilutions of antimony modulate cytokines production and macrophage - Leishmania (L.) amazonensis interaction in-vitro . Cytokine 2017; 92: 33-47
- 31 Cajueiro APB, Barbosa GM, Homsani F. et al. Evaluation of Leishmania infantum 30x biotherapy effects in the prevention and treatment of visceral leishmaniasis: in-vivo and in-vitro studies. Int J High Dilution Res 2016; 15: 26-29
- 32 Kesari AN, Kesari S, Singh SK, Gupta RK, Watal G. Studies on the glycemic and lipidemic effect of Murraya koenigii in experimental animals. J Ethnopharmacol 2007; 112: 305-311
- 33 Janbaz KH, Gilani AH. Studies on preventive and curative effects of berberine on chemical-induced hepatotoxicity in rodents. Fitoterapia 2000; 71: 25-33
- 34 Venkatesh PL, Dinakar A, Senthilkumar N. Hepatoprotective activity of an ethanolic extract of stems of Anisochilus carnosus against carbon tetrachloride induced hepatotoxicity in rats. Int J Pharm Sci 2011; 3: 243-245
- 35 Kaur G, Chauhan K, Kaur S. Lupeol induces immunity and protective efficacy in a murine model against visceral leishmaniasis. Parasitology 2019; 146: 1440-1450
- 36 Kashani MN, Firooz A, Eskandari SE. et al. Evaluation of meglumine antimoniate effects on liver, kidneys and pancreas function tests in patients with cutaneous leishmaniasis. Eur J Dermatol 2007; 17: 513-515
- 37 Kar S, Metz C, McMahon-Pratt D. CD4+ T cells play a dominant role in protection against New World leishmaniasis induced by vaccination with the P-4 amastigote antigen. Infect Immun 2005; 73: 3823-3827
- 38 Medina-Colorado AA, Osorio EY, Saldarriaga OA. et al. Splenic CD4+ T cells in progressive visceral Leishmaniasis show a mixed effector-regulatory phenotype and impair macrophage effector function through inhibitory receptor expression. PLoS One 2017; 12: e0169496
- 39 Kaushal H, Bras-Gonçalves R, Negi NS, Lemesre JL, Papierok G, Salotra P. Role of CD8+ T cells in protection against Leishmania donovani infection in healed Visceral Leishmaniasis individuals. BMC Infect Dis 2014; 14: 653
- 40 Nascimento KF, de Santana FR, da Costa CRV. et al. M1 homeopathic complex trigger effective responses against Leishmania (L) amazonensis in-vivo and in-vitro . Cytokine 2017; 99: 80-90
- 41 Cajueiro APB, Goma EP, Dos Santos HAM. et al. Homeopathic medicines cause Th1 predominance and induce spleen and megakaryocytes changes in BALB/c mice infected with Leishmania infantum . Cytokine 2017; 95: 97-101
- 42 Habib S, El Andaloussi A, Elmasry K. et al. PDL-1 blockade prevents T cell exhaustion, inhibits autophagy, and promotes clearance of Leishmania donovani . Infect Immun 2018; 86: e00019-e18