Longitudinal Metabolomics and Lipidomics Analyses Reveal Alterations Associated with Envenoming by Bothrops asper and Daboia russelii in an Experimental Murine Model

Toxins (Basel). 2022 Sep 23;14(10):657. doi: 10.3390/toxins14100657.

Abstract

Longitudinal metabolomics and lipidomics analyses were carried out on the blood plasma of mice injected intramuscularly with venoms of the viperid species Bothrops asper or 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 of metabolic pathways that showed those with the greatest change included aminoacyl tRNA synthesis and amino acid biosynthesis and metabolism pathways. With regard to lipid metabolism, there was an increase in triglycerides and some acyl carnitines and a concomitant 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.

Keywords: Bothrops asper; Daboia russellii; envenoming; lipidomics; metabolomics; snake venoms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism
  • Animals
  • Antivenins / pharmacology
  • Bothrops* / metabolism
  • Crotalid Venoms* / metabolism
  • Crotalid Venoms* / toxicity
  • Daboia* / metabolism
  • Disease Models, Animal
  • Heme / metabolism
  • Hydrocortisone
  • Lipidomics
  • Mice
  • Purines / metabolism
  • Pyrimidines / metabolism
  • RNA, Transfer / metabolism
  • Triglycerides / metabolism
  • Venoms / metabolism

Substances

  • Hydrocortisone
  • Venoms
  • Amino Acids
  • Purines
  • Heme
  • Triglycerides
  • Pyrimidines
  • RNA, Transfer
  • Crotalid Venoms
  • Antivenins

Grants and funding

This research and the APCs were funded by the Office of Research Core Administration, University of Virginia School of Medicine, Virginia, USA, and by Vicerrectoría de Investigación (Universidad de Costa Rica).