Oxidative pathways of chemical toxicity and oxidative stress biomarkers in marine organisms

Abstract

The antioxidant system of marine organisms consists of low molecular weight scavengers and antioxidant enzymes which interact in a sophisticated network. Environmental pollutants can unbalance this system through closely related mechanisms, indirect relationships and cascade effects acting from pre-transcriptional to catalytic levels. Chemically-mediated pathways have the potential to greatly enhance intracellular formation of reactive oxygen species (ROS); at the same time, excessive levels of oxyradicals down-regulate xenobiotics metabolism, with important environmental implications for organisms exposed to chemical mixtures. Interactions between different classes of chemicals, generation of ROS and onset of oxidative stress conditions are partly modulated by changes in levels and functions of redox-sensitive signaling proteins and transcription factors. The Nrf2-Keap1 pathway still remains largely unexplored in marine organisms, despite the elevated degree of identity and similarity with homolog transcripts and proteins from different species. Recent evidences on transcriptional up-regulation of this system are consistent with the capability to provide a prolonged expression of ARE-regulated cytoprotective genes, and to efficiently switch off this mechanism when oxidative pressure decreases. Although gene expression and catalytic activities of antioxidants are often measured as alternative biomarkers in monitoring biological effects of contaminants, conflicting results between molecular and biochemical responses are quite frequent. The links between effects occurring at various intracellular levels can be masked by non-genomic processes affecting mRNA stability and protein turnover, different timing for transcriptional and translational mechanisms, metabolic capability of tissues, post-transcriptional modifications of proteins, bi-phasic responses of antioxidant enzymes and interactions occurring in chemical mixtures. In this respect, caution should be taken in monitoring studies where mRNA levels of antioxidants could represent a snapshot of cell activity at a given time, not an effective endpoint of environmental pollutants.

Keywords: Antioxidants; Environmental pollutants; Marine organisms; Nrf2; Oxidative stress; ROS; Transcription factors.