The underestimated local effects of Micrurus corallinus venom revealed by gene expression and histopathological alterations.

The mechanisms of action of elapid neurotoxins have been widely studied; however, the pathophysiological effects of these venoms, particularly from coral snakes, have not been extensively investigated. To gain a deeper understanding of the mechanisms involved in the local and systemic toxicity of Micrurus corallinus venom and their genomic responses, we injected mice with 2.70 μg of venom, corresponding to a sub-lethal dose (50 % of the LD50), and evaluated the effects using transcriptomic and histopathological approaches. mRNA was extracted from the liver, spleen, kidney, heart, brain, diaphragm, and both right and left gastrocnemius muscles of control and treated animals and subjected to RNA sequencing (RNA-Seq) to perform functional analyses of differentially expressed genes (DEGs). In the right gastrocnemius, the site of venom injection, we observed significant histopathological changes characterized by a pronounced local inflammatory response. Consistent with these findings, enrichment analyses revealed 2454 DEGs in the right gastrocnemius, mostly involved in inflammatory pathways. Systemically, the liver emerged as the most affected non-local organ, showing over 400 DEGs containing several up-regulated genes involved in the production of acute phase proteins. These results underscore that inflammation possibly induced by the sub-lethal amounts of venom typically injected during human envenomation, and not only the neurotoxicity, could be a potentially deleterious effect of venom and should not be ruled out when diagnosing envenomation caused by coral snakes.