Molecular effectors in the chronic exposure to arsenic as early and sensitive biomarkers in developing Rhinella arenarum toads

MARDIROSIAN M.; CESCHIN D.G.; LASCANO CI; VENTURINO A

AQUATIC TOXICOLOGY

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2017 vol. 186 p. 19 - 27

0166-445X

Arsenic, a natural elementof ecological relevance, is one of the most toxic elements present in variousregions of the world. It can be found in natural water sources throughoutArgentina in concentrations between 0.01 and 15 mg L-1. The Argentineanautochthonous toad Rhinella arenarumwas selected to study the molecular mechanisms involved in the effects andresponse to the chronic As exposure along its embryonic and larval development.We evaluated the effects on MAPK signal transduction pathway and transcriptionfactors c-FOS and c-JUN, and the regulation of the expression at protein levelsof different antioxidant enzymes. Our results indicated that As is modulatingthe MAPK pathway, increasing MEK and ERK levels both in the nuclear and post-nuclearfraction along the embryonic development and mainly at the beginning of thelarval stage. Through this pathway, As can upregulate transcription factorslike c-FOS and c-JUN, impacting the antioxidant response of the exposed embryosand larvae through antioxidant enzymes and recycling of GSH. Arsenic triggeredspecifically the synthesis of antioxidant enzymes in exposed R. arenarum embryo and larvae. Inparticular, the expression levels of SOD, CAT and GST enzymes analyzed byWestern blot showed a similar behavior to their enzymatic activities in ourprevious work. This fact suggests that not only the synthesis of theseantioxidant enzymes but also their rapid degradation after inactivation wouldbe regulated in response to ROS levels. Antioxidant enzymes may show dualresponses of induction and inactivation followed by degradation depending onthe levels of oxidative stress and impact on ROS targets when the exposure issustained in time and intensity. We also performed a probability of exceedence analysisincluding our previous results to visualize a progression of the response intime and also established the best early-responding biomarkers at the lowest Asconcentrations. As a conclusion, the molecular biomarkers such as the MAPKs MEKand ERK and transcription factors c-FOS and c-JUN are early induced in theresponse of developing toad embryos exposed to very low As concentrations inwater. The advantage of counting with molecular biomarkers early responding tolow concentrations of As in a chronic exposure is that they may anticipate the irreversible damage at later developmental stages due to the constant oxidative challenge.