Interactions between genes altered during cardiotoxicity and neurotoxicity in zebrafish revealed using induced network modules analysis

Abstract

As the manufacturing and development of new synthetic compounds increase to keep pace with the expanding global demand, adverse health effects due to these compounds are emerging as critical public health concerns. Zebrafish have become a prominent model organism to study toxicology due to their genomic similarity to humans, optical clarity, well-defined developmental stages, short generation time, and cost-effective maintenance. It also provides a shorter time frame for in vivo toxicology evaluation compared to the mammalian experimental systems. Here, we used meta-analysis to examine the alteration in genes during cardiotoxicity and neurotoxicity in zebrafish, caused by chemical exposure of any kind. First, we searched the literature comprehensively for genes that are altered during neurotoxicity and cardiotoxicity followed by meta-analysis using ConsensusPathDB. Since constant communication between the heart and the brain is an important physiological phenomenon, we also analyzed interactions among genes altered simultaneously during cardiotoxicity and neurotoxicity using induced network modules analysis in ConsensusPathDB. We observed inflammation and regeneration as the major pathways involved in cardiotoxicity and neurotoxicity. A large number of intermediate genes and input genes anchored in these pathways are molecular regulators of cell cycle progression and cell death and are implicated in tumor manifestation. We propose potential predictive biomarkers for neurotoxicity and cardiotoxicity and the major pathways potentially implicated in the manifestation of a particular toxicity phenotype.