Avaliação dos efeitos neurotóxicos do ferro in vivo em caenorhabditis elegans

Abstract

Iron (F e) is an important metal to the organism homeostasis and exists abundantly in the environment. Moderate levels of Fe obtained from food are necessary for normal cell physiology; however, abnormally high levels of Fe(II)/Fe(III) can be cytotoxic effects via reducing H2O2 to the highly cytotoxic hydroxyl radical (OH•) (Fenton catalysis). Consequently leading to oxidative stress. Fe is ubiquitous toxicant in the environment and also widely used in food products, however its effects to the nervous system is not well understood. Seeking for alternative experimental models that may substitute and offer new possibilities to assay xenobiotics toxicity, the nematode Caenorhabditis elegans has been found favorable as a valuable bioindicator organism. Hence, this study evaluated the toxic effects of Fe using C. elegans and investigating different parameters in order to contribute to the investigation of Fe-induced toxicity and to validate this model aiming, ultimately, the search for therapeutic targets that are more effective than those currently used. Our study depicted that the Fe LD50 in acute exposure (30min) was 1.2 mM, as we verified that worms can uptake this metal. Furthermore, sublethal Fe concentrations decreased significantly the worms lifespan and brood size compared to non-exposed worms. We also observed that animals exposed to Fe showed decreased locomotor activity and decreased mechanic sensitivity, which suggests possible dysfunction of the nervous system. In agreement, we found cholinergic and dopaminergic alterations in the worms. In summary, we suggest that iron exposure leads to damage of certain neurons, which could be the cause of altered behavior and of the defects of reproduction.