The Metabolomic Profiles of Sera of Mice Infected with Plasmodium berghei and Treated by Effective Fraction of Naja naja oxiana Using 1H Nuclear Magnetic Resonance Spectroscopy.

Abstract

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. We sought to ascertain both safety and anti-parasitic effects of experimental therapies. After purification of the venom fractions, 25 mice were infected, then treated for 4days with 0.2ml of 5mg/kg, 2.5mg/kg and 1mg/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. A clear inhibitory effect on parasitaemia was observed (with 75% inhibition with 5mg/kg and 50% reduction when 2.5mg/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. 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.