Gheyath K Nasrallah1, Rola Salem2, Sahar Da'as3, Ola Loay Ahmad Al-Jamal2, Mark Scott4, Ibrahim Mustafa5. 1. Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar; Biomedical Research Centre, Qatar University, Doha, Qatar. 2. Biomedical Research Centre, Qatar University, Doha, Qatar. 3. Sidra Medical and Research Centre, Doha, Qatar; Hamad bin Khalifa University, Doha, Qatar. 4. Centre for Blood Research, University of British Columbia, Vancouver, Canada. 5. Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar. Electronic address: ibrahim.mustafa@qu.edu.qa.
Abstract
OBJECTIVES: Clinically approved iron chelators are effective in decreasing significant transfusional iron accumulation. Starch-Deferoxamine (S-DFO), a novel high molecular weight iron chelator, was produced to increase binding capacity to iron and reduce toxicity. Although its efficacy was established in one small cohort clinical trial, its potential adverse effect was not adequately addressed. METHODS: We utilized zebrafish model to assess S-DFO toxicity using following assays: mortality, teratogenicity, hatching rate, tail flicking, Acridine Orange staining for apoptosis detection, o-dianisidine staining for hemoglobin synthesis, and the level of Hsp70 as a general stress indicator. Embryos were exposed to different concentrations of S-DFO, Zinc Oxide nanoparticle (ZnO) (positive control), along with untreated control (UC). RESULTS: S-DFO showed no significant mortality nor deformities at all tested concentrations (0.0-1000 μM). Thus, the LC50 is expected to >1000 μM. 100 μM S-DFO treatment did not affect embryo development (as judged by hatching rate); neuromuscular activity (as judged by tail flicking); and hemoglobin synthesis. Neither apoptosis, nor increase in Hsp70 level was noticed upon S-DFO treatment. CONCLUSION: Our assays demonstrate that S-DFO does not induce cellular or biochemical stress and has no adverse effect on organ development of zebrafish embryos, suggesting its safe use as an iron chelator.
OBJECTIVES: Clinically approved iron chelators are effective in decreasing significant transfusional iron accumulation. Starch-Deferoxamine (S-DFO), a novel high molecular weight iron chelator, was produced to increase binding capacity to iron and reduce toxicity. Although its efficacy was established in one small cohort clinical trial, its potential adverse effect was not adequately addressed. METHODS: We utilized zebrafish model to assess S-DFOtoxicity using following assays: mortality, teratogenicity, hatching rate, tail flicking, Acridine Orange staining for apoptosis detection, o-dianisidine staining for hemoglobin synthesis, and the level of Hsp70 as a general stress indicator. Embryos were exposed to different concentrations of S-DFO, Zinc Oxide nanoparticle (ZnO) (positive control), along with untreated control (UC). RESULTS:S-DFO showed no significant mortality nor deformities at all tested concentrations (0.0-1000 μM). Thus, the LC50 is expected to >1000 μM. 100 μM S-DFO treatment did not affect embryo development (as judged by hatching rate); neuromuscular activity (as judged by tail flicking); and hemoglobin synthesis. Neither apoptosis, nor increase in Hsp70 level was noticed upon S-DFO treatment. CONCLUSION: Our assays demonstrate that S-DFO does not induce cellular or biochemical stress and has no adverse effect on organ development of zebrafish embryos, suggesting its safe use as an iron chelator.
Authors: Nadin Younes; Bana S Alsahan; Asmaa J Al-Mesaifri; Sahar I Da'as; Gianfranco Pintus; Amin F Majdalawieh; Gheyath K Nasrallah Journal: Toxicol Res (Camb) Date: 2021-12-21 Impact factor: 3.524