Longitudinal metabolomics and lipidomics analyses reveal markers of envenoming by Bothrops asper and Daboia russelii in an experimental murine model

Longitudinal metabolomics and lipidomics analysis was carried out in the blood plasma of mice injected intramuscularly with venoms of the viperid species Bothrops asper and Daboia russelii. Blood samples were collected 1, 3, 6 and 24 h after venom injection, and a control group of non-envenomed mice was included. Significant perturbations in metabolomics and lipidomics were observed at 1, 3 and 6 h, while values returned close to those of control mice by 24 h, hence reflecting a transient pattern of metabolic disturbance. Both venoms induced significant changes in amino acids, as well as in several purines and pyrimidines, and in some metabolites of the tricarboxylic acid cycle. KEGG analysis identified metabolic pathways that showed the highest changes, i.e., aminoacyl tRNA synthesis and amino acid biosynthesis and metabolism pathways. Regarding lipid metabolism, there was an increase of triglycerides and some acyl carnitines, concomitantly with a drop in the levels of some phospholipids. In addition, envenomed mice had higher levels of cortisol, heme and some oxidative stress markers. The overall pattern of metabolic changes in envenomed mice bears similarities with the patterns described in several traumatic injuries, thus underscoring a metabolic response/adaptation to the injurious action of the venoms.