Avaliação do Potencial citotóxico e genotóxico do Fe (II) E FeSO4 em cultura de células mononucleares de sangue periférico humano: riscos versos segurança em suplementação prolongada

Abstract

Iron (Fe) is an indispensable trace element for human body homeostasis, and its plasma decrease competes for the establishment of relevant clinical conditions. The pharmacological therapy and feed enrichment conducts use iron-based salts to treat and prevent sideropenia. However, if not properly monitored, these conducts can generate hyperferremia conditions. Nevertheless, the literature exhaustively describes the induction of tissue damage caused by the excess of iron basing it with the increase of oxidative stress. Nonetheless, very little is known about the relationship between Fe concentrations and damages to the human genetic material. The objective of this study was to compare the cytotoxic, genotoxic and mutagenic effects of Fe (II) and FeSO4 in human peripheral blood mononuclear cells culture at 1, 2, 5 and 10 μg / mL concentrations, through cell viability analysis, cell proliferation, comet and micronucleus assay, as well as to indicate the concentration where the onset of lesions was observed. Both the Fe (II) and FeSO4 showed no cytotoxicity. On the other hand, the comet assay demonstrated that Fe (II) induced an increase in DNA damage of approximately 30-times to that observed for the negative control; while FeSO4 generated an even greater damage, around 60 times (p <0.001). In the micronucleus test, Fe (II) increased in the micronuclei frequency from 2.5 to 6 times the rate encountered for the negative control; while the increasing in the micronuclei frequency by FeSO4 ranged from 6 to 12 times (p<0.05). It can be noted that, for these last two trials, the lesions initiated at 1 μg / mL concentration, in other words, really close to the plasmatic peak (approximately 1,33 μg/mL) to a habitual therapeutic dose of FeSO4 (40 mg / day). These findings draw attention to the adequate clinical monitoring of people who require Fe-based supplementation, in detriment of injuries to their genetic material. It is suggested complementary studies to elucidate the mechanisms involved in the phenomena observed and evaluations with other cell types and in vivo assays (trials) to confirm the intensity of the lesions.