Embryonic Zebrafish Model - A Well-Established Method for Rapidly Assessing the Toxicity of Homeopathic Drugs - Toxicity Evaluation of Homeopathic Drugs Using Zebrafish Embryo Model -
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Objectives: Advancements in nanotechnology have led to nanoparticle (NP) use in various fields of medicine. Although the potential of NPs is promising, the lack of documented evidence on the toxicological effects of NPs is concerning. A few studies have documented that homeopathy uses NPs. Unfortunately, very few sound scientific studies have explored the toxic effects of homeopathic drugs. Citing this lack of high-quality scientific evidence, regulatory agencies have been reluctant to endorse homeopathic treatment as an alternative or adjunct treatment. This study aimed to enhance our insight into the impact of commercially-available homeopathic drugs, to study the presence of NPs in those drugs and any deleterious effects they might have, and to determine the distribution pattern of NPs in zebrafish embryos (Danio rerio). Methods: Homeopathic dilutions were studied using high-resolution transmission electron microscopy with selected area electron diffraction (SAED). For the toxicity assessment on Zebrafish, embryos were exposed to a test solution from 4 - 6 hours post-fertilization, and embryos/larvae were assessed up to 5 days post-fertilization (dpf) for viability and morphology. Toxicity was recorded in terms of mortality, hatching delay, phenotypic defects and metal accumulation. Around 5 dpf was found to be the optimum developmental stage for evaluation. Results: The present study aimed to conclusively prove the presence of NPs in all high dilutions of homeopathic drugs. Embryonic zebrafish were exposed to three homeopathic drugs with two potencies (30CH, 200CH) during early embryogenesis. The resulting morphological and cellular responses were observed. Exposure to these potencies produced no visibly significant malformations, pericardial edema, and mortality and no necrotic and apoptotic cellular death. Conclusion: Our findings clearly demonstrate that no toxic effects were observed for these three homeopathic drugs at the potencies and exposure times used in this study. The embryonic zebrafish model is recommended as a well-established method for rapidly assessing the toxicity of homeopathic drugs.
Abstract
Objectives: Advancements in nanotechnology have led to nanoparticle (NP) use in various fields of medicine. Although the potential of NPs is promising, the lack of documented evidence on the toxicological effects of NPs is concerning. A few studies have documented that homeopathy uses NPs. Unfortunately, very few sound scientific studies have explored the toxic effects of homeopathic drugs. Citing this lack of high-quality scientific evidence, regulatory agencies have been reluctant to endorse homeopathic treatment as an alternative or adjunct treatment. This study aimed to enhance our insight into the impact of commercially-available homeopathic drugs, to study the presence of NPs in those drugs and any deleterious effects they might have, and to determine the distribution pattern of NPs in zebrafish embryos (Danio rerio). Methods: Homeopathic dilutions were studied using high-resolution transmission electron microscopy with selected area electron diffraction (SAED). For the toxicity assessment on Zebrafish, embryos were exposed to a test solution from 4 - 6 hours post-fertilization, and embryos/larvae were assessed up to 5 days post-fertilization (dpf) for viability and morphology. Toxicity was recorded in terms of mortality, hatching delay, phenotypic defects and metal accumulation. Around 5 dpf was found to be the optimum developmental stage for evaluation. Results: The present study aimed to conclusively prove the presence of NPs in all high dilutions of homeopathic drugs. Embryonic zebrafish were exposed to three homeopathic drugs with two potencies (30CH, 200CH) during early embryogenesis. The resulting morphological and cellular responses were observed. Exposure to these potencies produced no visibly significant malformations, pericardial edema, and mortality and no necrotic and apoptotic cellular death. Conclusion: Our findings clearly demonstrate that no toxic effects were observed for these three homeopathic drugs at the potencies and exposure times used in this study. The embryonic zebrafish model is recommended as a well-established method for rapidly assessing the toxicity of homeopathic drugs.
참고문헌 (31)
- Bellavite P, "A scientific reappraisal of the ‘principle of similarity’", Med Hypotheses, 49(3), pp.203~212 (1997)
- Bellavite P, "The emerging science of homeopathy", pp.424~ (2002), North Atlantic
- Teixeira MZ, "Paradoxical strategy for treating chronic diseases’: a therapeutic model used in homeopathy for more than two centuries", Homeopathy, 94(4), pp.265~266 (2005)
- Roduner E, "Size matters: why nanomaterials are different", Chem Soc Rev, 35(7), pp.583~592 (2006)
- Chikramane PS, "Extreme homeopathic dilutions retain starting materials: a nanoparticulate perspective", Homeopathy, 99(4), pp.231~242 (2010)
- Sharma A, "Identification of medicinally active ingredient in ultradiluted Digitalis purpurea: fluorescence spectroscopic and cyclic-voltammetric study", J Anal Methods Chem, 2012 (2012)[DOI]
- Bellavite P, "The emerging science of homeopathy: complexity, biodynamics and nanopharmacology", pp.424~ (1995), North Atlantic Books
- Dantas F, "Do homeopathic medicines provoke adverse effects? a systematic review", Br Homeopath J, 89(S1), pp.S35~S38 (2000)
- Posadzki P, "Adverse effects of homeopathy: a systematic review of published case reports and case series", Int J Clin Pract, 66(12), pp.1178~1188 (2012)
- Vickers AJ, "Independent replication of pre-clinical research in homoeopathy: a systematic review", Forsch Komplementarmed, 6(6), pp.311~320 (2004)
- Barve R, "Size-dependent in vivo", in vitro results of homoeopathic herbal extracts, 2013, pp.3(1), 18~
- Goldsmith P, "Zebrafish as a pharmacological tool: the how, why and when", Curr Opin Pharmacol, 4(5), pp.504~512 (2004)
- Rubinstein AL, "Zebrafish assays for drug toxicity screening", Expert Opin Drug Metab Toxicol, 2(2), pp.231~240 (2006)
- Winter MJ, "Validation of a larval zebrafish locomotor assay for assessing the seizure liability of early-stage development drugs", J Pharmacol Toxicol Methods, 57(3), pp.176~187 (2008)
- Postlethwait JH, "Zebrafish comparative genomics and the origins of vertebrate chromosomes", Genome Res, 10(12), pp.1890~1902 (2000)
- Redfern WS, "Zebrafish assays as early safety pharmacology screens: paradigm shift or red herring", J Pharmacol Toxicol Methods, 58(2), pp.110~117 (2008)
- Parng C, "Zebrafish : a preclinical model for drug screening", Assay Drug Dev Technol, 1(1), pp.41~48 (2002)
- Shaukat Ali, "Large-Scale Assessment of the Zebrafish Embryo as a Possible Predictive Model in Toxicity Testing", PLoS ONE, 6(6), pp.e21076~ (2011), Public Library of Science (PLoS)[DOI]
- McGrath P, "Zebrafish: a predictive model for assessing drug-induced toxicity", Drug Discov Today, 13(9-10), pp.394~401 (2008)
- Bell IR, "Nanoparticle characterization of traditional homeopathically- manufactured silver (Argentum metallicum) medicines and placebo controls", Journal of Nanomedicine & Nanotechnology, 06(04) (2015), OMICS Publishing Group[DOI]
- Westerfield M, "A guide for the laboratory use of zebrafish danio (brachydanio) rerio" (2000), University of Oregon Press
- "Test no. 236: fish embryo acute toxicity (FET) test" (2016)[URL]
- Hu YL, "Toxicity evaluation of biodegradable chitosan nanoparticles using a zebrafish embryo model", Int J Nanomedicine, 6, pp.3351~3359 (2011)
- Chikramane PS, "Why extreme dilutions reach non-zero asymptotes: a nanoparticulate hypothesis based on froth flotation", Langmuir, 28(45), pp.15864~15875 (2012)
- Upadhyay RP, "Homeopathy emerging as nanomedicine", International Journal of High Dilution Research, 10(37), pp.299~310 (2011)
- Demangeat JL, "NMR relaxation evidence for solute- induced nanosized superstructures in ultramolecular aqueous dilutions of silica–lactose", J Mol Liq, 155(2-3), pp.71~79 (2010)
- Rajendran ES, "Field emission scanning electron microscopic (FESEM) and energy dispersive spectroscopic (EDS) studies of centesimal scale potencies of the homeopathic drug Lycopodium clavatum", AJHM, 108(1), pp.9~18 (2015)
- Konovalov A, "Highly diluted aqueous solutions: formation of nano-sized molecular assemblies (nanoassociates)", Geochem Int, 52(13), pp.1207~1226 (2014)
- Linde K, "Critical review and meta-analysis of serial agitated dilutions in experimental toxicology", Hum Exp Toxicol, 13(7), pp.481~492 (1994)
- Makri A, "Children’s susceptibility to chemicals : a review by developmental stage", J Toxicol Environ Health, Part B, 7(6), pp.417~435 (2004)
- "Fun with homeopaths and meta-analyses of homeopathy trials" (2008)[URL]