BackgroundParkinson’s disease (PD) is the second most common neurodegenerative disorder. In addition to its highly debilitating motor symptoms, non-motor symptoms may precede their motor counterparts by many years, which may characterize a prodromal phase of PD. A potential pharmacological strategy is to introduce neuroprotective agents at an earlier stage in order to prevent further neuronal death. N-acetylcysteine (NAC) has been used against paracetamol overdose hepatotoxicity by restoring hepatic concentrations of glutathione (GSH), and as a mucolytic in chronic obstructive pulmonary disease by reducing disulfide bonds in mucoproteins. It has been shown to be safe for humans at high doses. More recently, several studies have evidenced that NAC has a multifaceted mechanism of action, presenting indirect antioxidant effect by acting as a GSH precursor, besides its anti-inflammatory and neurotrophic effects. Moreover, NAC modulates glutamate release through activation of the cystine-glutamate antiporter in extra-synaptic astrocytes. Its therapeutic benefits have been demonstrated in clinical trials for several neuropsychiatric conditions but has not been tested in PD models yet.MethodsIn this study, we evaluated the potential of NAC to prevent the damage induced by 6-hydroxydopamine (6-OHDA) on motor, optomotor and morphological parameters in a PD model in larval zebrafish.ResultsNAC was able to prevent the motor deficits (total distance, mean speed, maximum acceleration, absolute turn angle and immobility time), optomotor response impairment and morphological alterations (total length and head length) caused by exposure to 6-OHDA, which reinforce and broaden the relevance of its neuroprotective effects.DiscussionNAC acts in different targets relevant to PD pathophysiology. Further studies and clinical trials are needed to assess this agent as a candidate for prevention and adjunctive treatment of PD.

We report on the effect of different coatings (dextran, chitosan, polyethylene glycol, carboxy-silane, and silica) in the toxicity elicited by superparamagnetic iron oxide nanoparticles (SPIONs) in the developing zebrafish (Danio rerio). Animals were exposed to nanoparticle concentrations ranging from 0.125 to 8.0 mM of Fe during the first 5 days after fertilization. Embryotoxicity parameters (survival, hatching rate, and the incidence of anatomical malformations) and behavioral patterns (locomotion during the exploration of a new environment, thigmotaxis, and the escape response to an aversive stimulus) were evaluated. Exposed embryos hatched between 48 and 72 hpf, as expected for the species, but tendencies of either acceleration or delay were observed, depending on the nanoparticle coating. Malformations in exposed and control groups were similar, independent of the coating. Mortality rates were also not significantly affected by exposure to most of the coated SPIONs, except for animals treated with chitosan-coated nanoparticles, which induced 100% mortality at concentrations higher than 2 mM. A similar trend was observed in the behavioral parameters, in which significant adverse effects were mostly caused by chitosan-coated nanoparticles even at low concentrations. The higher toxicity observed for chitosan-coated particles raises concern and deserves further mechanistic investigations, considering the ample use of this compound in pharmaceutical and biomedical applications.

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