Avaliação ecotoxicológica do fumarato de tenofovir desoproxila sobre Biomphalaria glabrata, in vivo e in vitro.

Abstract

Tenofovir Disoproxil Fumarate (TDF) is a drug commonly used in the treatment of human immunodeficiency virus (HIV). Due to its resistance to metabolism by biological systems, up to 80% of the drug dose can be eliminated unchanged in the urine within 72 hours after administration. It is known that TDF is present in surface water bodies and that conventional sewage treatment is inefficient in eliminating this drug and its metabolites. Even so, little information about the environmental impact of this drug is available in the scientific literature. Thus, the objective of this work was to evaluate the potential in vitro and in vivo cytotoxic effects of TDF on the snail Biomphalaria glabrata and its hemocytes. To perform the assay, an in vitro analysis was initially performed, in which the hemocytes were exposed to different concentrations of the drug, for 1 hour, and evaluated for its viability, metabolic activity and cellular phagocytosis. Subsequently, an in vivo evaluation was performed, where 30 snails per group were exposed to the same concentrations in vitro, for 72 hours (acute exposure) and 21 days (chronic exposure). During exposure, they were monitored daily and evaluated for mortality and behavioral changes. After exposure, the snails were sacrificed and their hemolymph collected to assess nitric oxide production, metabolic and phagocytic activity and hemocyte viability. The results obtained by the in vitro assay showed that TDF is capable of significantly stimulating the phagocytic and metabolic activity of hemocytes when compared to the control, at concentrations higher than 30 µg/L. Likewise, from the in vivo assay, this same stimulus was observed at concentrations above 30 mg/L, in addition to an increase in nitric oxide production. However, due to the persistence of this stimulus, an increase in nonviable hemocytes and a reduction in their concentration in the hemolymph was observed after 21 days of exposure. On the other hand, at all concentrations tested, it was not possible to observe an increase in snail mortality, only behavioral changes. From the data obtained by this study, it was possible to observe the TDF residue at concentrations of 300 mg/L, 30 mg/L and 3 mg/L it is toxic to the snail in the long term. Furthermore, the evaluation of hemolymph revealed that this exposure causes a significant reduction in the concentration and viability of circulating hemocytes.