Fateme Hajialiani1, Delavar Shahbazzadeh2, Fatemeh Maleki3, Taher Elmi4, Fatemeh Tabatabaie5, Zahra Zamani6. 1. Department of Medical Parasitology, School of Medicine-International Campus, Iran University of Medical Sciences, Tehran, Iran. 2. Department of Medical Biotechnology, Laboratory of Venom and Bio Therapeutics Molecules, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran. 3. Department of Parasitology, Faculty of Para Medical Sciences, Iran University of Medical Sciences, Tehran, Iran. 4. Department of Laboratory Science, Islamic Azad University, Babol Branch, Babol, Iran. 5. Department of Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. tabatabaei.f@iums.ac.ir. 6. Biochemistry Department, Pasteur Institute of Iran, Pasteur Avenue, Tehran, Iran. zamani@pasteur.ac.ir.
Abstract
BACKGROUND: The use of venom fractions from the Iranian cobra could be useful adjunct treatments of malaria with chloroquine. A metabolomic investigation with 1HNMR spectroscopy was conducted on an effective fraction tested earlier using Plasmodium berghei as an experimental murine model. PURPOSE: We sought to ascertain both safety and anti-parasitic effects of experimental therapies. METHODS: After purification of the venom fractions, 25 mice were infected, then treated for 4 days with 0.2 ml of 5 mg/kg, 2.5 mg/kg and 1 mg/kg of the effective fraction, chloroquine, and a drug vehicle. An ED50 was obtained using Giemsa staining and real-time PCR analysis. The toxicity tests inspecting both liver and kidney tissues were performed. RESULTS: A clear inhibitory effect on parasitaemia was observed (with 75% inhibition with 5 mg/kg and 50% reduction when 2.5 mg/kg dosage used). ED50 obtained 2.5 mg/kg. The metabolomics were identified as differentiation of aminoacyl-t-RNA biosynthesis, valine, leucine, isoleucine biosynthesis and degradation pathways were observed. CONCLUSION: Upon therapeutic effects of cobra venom fraction, further optimization of dose-dependent response of pharmacokinetics would be worthwhile for further exploration in adjunct experimental venom therapies.
BACKGROUND: The use of venom fractions from the Iranian cobra could be useful adjunct treatments of malaria with chloroquine. A metabolomic investigation with 1HNMR spectroscopy was conducted on an effective fraction tested earlier using Plasmodium berghei as an experimental murine model. PURPOSE: We sought to ascertain both safety and anti-parasitic effects of experimental therapies. METHODS: After purification of the venom fractions, 25 mice were infected, then treated for 4 days with 0.2 ml of 5 mg/kg, 2.5 mg/kg and 1 mg/kg of the effective fraction, chloroquine, and a drug vehicle. An ED50 was obtained using Giemsa staining and real-time PCR analysis. The toxicity tests inspecting both liver and kidney tissues were performed. RESULTS: A clear inhibitory effect on parasitaemia was observed (with 75% inhibition with 5 mg/kg and 50% reduction when 2.5 mg/kg dosage used). ED50 obtained 2.5 mg/kg. The metabolomics were identified as differentiation of aminoacyl-t-RNA biosynthesis, valine, leucine, isoleucine biosynthesis and degradation pathways were observed. CONCLUSION: Upon therapeutic effects of cobra venom fraction, further optimization of dose-dependent response of pharmacokinetics would be worthwhile for further exploration in adjunct experimental venom therapies.
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