Toxicity of the 3,4- methylenedioxymethamphetamine (MDMA) and its enantiomers to Daphnia magna, after isolation by semipreparative chromatography
Costa, Ana Rita Fernandes Miranda da
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Psychoactive substances (PAS) have been frequently documented in aquatic systems causing oncern for their potential to interfere with biochemical, cellular, physiological,and behavioural mechanisms of non-target organisms. 3,4-Methylenedioxymethamphetamine (MDMA) is among the most consumed PAS in theworld. However, the United States Food and Drugs Administration (USFDA) recentlyapproved a trial to assess its pharmacological potential in patients with post-traumaticstress disorder. MDMA is a chiral substance, sold on the illicit market exclusively as a racemate (R,SMDMA).After consumption, human metabolism is enantioselective, S(+)-MDMA undergo preferential metabolism over R(−)-MDMA, which leads to enrichment of the R(−)-enantiomer in excretions. Its occurrence in the environment arises from directdisposal of sewage, clandestine laboratories or ischarges of effluents from Wastewater Treatment Plants (WWTPs) due to the ineficciency of WWTP to complete eliminatedrugs residues. Studies on the toxicity of this compound in non-target organisms are scarce and lack of information on enantioselectivity. Thus, the objective of this work was to evaluate the enantioselective potential on MDMA toxicity using Daphnia magna as a freshwater animal model. For this, the MDMA enantiomers were separated by semi-preparativechromatography using a semi-preparative column with amylose tris-3,5-dimethylphenylcarbamate adsorbed on minopropyl silica (APS-Nucleosil - 500 Å, 7 μm; 20% g/ g). Enantiomers were obtained with an enantiomeric purity > 97% and used inecotoxicity assay. The sub-chronic assay was initiated with neonates (< 24 h, day 0) through day 8, using three concentrations for the racemate, 0.1, 1.0 and 10.0 μg/L, two concentrations for the enantiomers (0.1 and 1.0 μg/L) and a control group. Each experimental unit consisted of a group of 15 organisms and 5 replicates for each concentration or control and morphophysiological, behavioural, reproductive and biochemical parameters were determined at different stages of the organism'sdevelopment. Changes were observed for some of the analyzed parameters as well as enantioselectivity. For example, an increase in body size was observed in organisms exposed to (R,S)-MDMA at day 8 (adults) and an enantioselective effect with significantly reduced body growth in organisms xposed to the S(+)-enantiomer also at day 8 (adults). Changes in ii swimming behaviour were observed with increasing swimming speed and total distance travelled in organisms exposed to (R,S)-MDMA at all concentrations. On the contrary, a decrease in the total distance travelled was observed in organisms exposed to the enantiomers but enantioselective effects were not observed. No reproductive or biochemical changes were observed in either racemate or enantiomer exposure except for acetylcholinesterase and catalase activity, whose activity decreased in organisms exposed to the highest concentration of (R,S)-MDMA (10 μg/L). This study demonstrated that MDMA can affect the development and swimming behaviour of daphnia including at environmental concentrations and that these effects may be enantioselective, but no reproductive and biochemical changes were observed for the majority of the parameters analysed. However, it is essential to carry out additional studies to complement the resultsobtained, for an accurate assessment of the potential environmental risks of thissubstance.