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

Background: The use of venom fractions from the Iranian cobra could be useful adjunct treatments of malaria with chloroquine. A metabolomic investigation with HNMR 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.