Molecular Mechanisms and Biomarker-Based Early-Warning Indicators of Heavy Metal Toxicity in Marine Fish
Andra Oros, Valentina Coatu, Nicoleta Damir, Diana Danilov, Elena Ristea, Luminița Lazăr
Abstract
Heavy metals are among the most persistent and bioaccumulative pollutants in marine ecosystems, posing significant toxicological threats to fish via complex molecular and cellular disruptions. This review synthesizes current knowledge on the cascade of mechanistic responses in marine fish following HM exposure, which includes oxidative stress, modulation of antioxidant responses, activation of detoxification systems, DNA damage, inflammation, apoptosis, neuroendocrine disruption, and ultimately, cellular energy imbalance. In addition to established pathways, the review highlights recent advances in mechanistic understanding and biomarker development, including cellular stress responses, epigenetic regulation, metal homeostasis mechanisms, and novel molecular indicators. These mechanisms support the development of an integrated biomarker framework that combines classical indicators (e.g., antioxidant enzymes, metallothionein) with next-generation endpoints (e.g., miRNA profiles, gene-level responses of metal transporters or stress chaperones, epigenetic alterations). The interpretation of biomarker responses requires consideration of the exposure context, environmental variables, and physiological status to ensure accurate assessment of sublethal toxicity in field settings. By bridging mechanistic understanding with biomonitoring relevance, this review provides a comprehensive foundation for advancing molecular tools in pollution monitoring and risk assessment. Special emphasis is placed on biomarkers specific to heavy metal exposure, enhancing their diagnostic value relative to general stress indicators.