Improvement of non-motor and motor behavioral alterations associated with Parkinson-like disease in Drosophila melanogaster: Comparative effects of treatments with hesperidin and L-dopa.

Non-motor alterations such as anxiety and memory deficit may represent early indications of Parkinson's disease (PD), and therapeutic strategies that reduce non-motor alterations are promising alternatives for the treatment. Therefore, the search for natural compounds that act on motor and non-motor complications is highly relevant. In this sense, we demonstrated the role of hesperidin (Hsd) as a citrus flavonoid and its pharmacological properties as an antioxidant and neuroprotective agent. Our objective was to evaluate Hsd in developing motor and non-motor alterations in a Drosophila melanogaster model of Parkinson-like disease induced by iron (Fe) exposure. The flies were divided into six groups: control, Hsd (10 µM), L-dopa (positive control, 1 mM), Fe (1 mM), Fe + Hsd, and Fe + L-dopa. Motor coordination tests, memory assessment through aversive phototaxy, and anxiety-like behaviors characterized in flies, such as grooming and aggressiveness, were performed. The Hsd attenuated motor and non-motor alterations, such as motor coordination, memory deficits and anxiety-like behaviors, attenuated monoaminergic deficits, and lowered Fe levels in the head of flies. In addition, Hsd prolonged the life of the flies, thereby standing out from the L-dopa-treated group. Thus, Hsd can protect the dopaminergic system from insults caused by Fe, preventing non-motor alterations in PD; Hsd also reduced Fe levels in the flies' heads, suggesting that iron chelation may represent an important mechanism of action, in addition to its antioxidant action.

Iron overload during the embryonic period develops hyperactive like behavior and dysregulation of biogenic amines in Drosophila melanogaster.

Iron (Fe) is used in various cellular functions, and a constant balance between its uptake, transport, storage, and use is necessary to maintain its homeostasis in the body. Changes in Fe metabolism with a consequent overload of this metal are related to neurological changes and cover a broad spectrum of diseases, mainly when these changes occur during the embryonic period. This work aimed to evaluate the effect of exposure to Fe overload during the embryonic period of Drosophila melanogaster. Progenitor flies (male and female) were exposed to ferrous sulfate (FeSO4) for ten days in concentrations of 0.5, 1, and 5 â€‹mM. After mating and oviposition, the progenitors were removed and the treatment bottles preserved, and the number of daily hatches and cumulative hatching of the first filial generation (F1) were counted. Subsequently, F1 flies (separated by sex) were subjected to behavioral tests such as negative geotaxis test, open field test, grooming, and aggression test. They have evaluated the levels of dopamine (DA), serotonin (5-HT), octopamine (OA), tryptophan and tyrosine hydroxylase (TH), acetylcholinesterase, reactive species, and the levels of Fe in the progenitor flies and F1. The Fe levels of F1 flies are directly proportional to what is incorporated during the period of embryonic development; we also observed a delay in hatching and a reduction in the number of the hatch of F1 flies exposed during the embryonic period to the 5mM Fe diet, a fact that may be related to the reduction of the cell viability of the ovarian tissue of progenitor flies. The flies exposed to Fe (1 and 5 â€‹mM) showed an increase in locomotor activity (hyperactivity) and a significantly higher number of repetitive movements. In addition to a high number of aggressive encounters when compared to control flies. We can also observe an increase in the levels of biogenic amines DA and 5-HT and an increase in TH activity in flies exposed to Fe (1 and 5 â€‹mM) compared to the control group. We conclude that the hyperactive-like behavior demonstrated in both sexes by F1 flies exposed to Fe may be associated with a dysregulation in the levels of DA and 5-HT since Fe is a cofactor of TH, which had its activity increased in this study. Therefore, more attention is needed during the embryonic development period for exposure to Fe overload.

Are there feasible strategies for determining bromine and iodine in human hair using interference-free plasma based-techniques?

An effective analytical method for bromine and iodine determination in human hair using interference-free inductively coupled plasma mass spectrometry (ICP-MS) was developed. Human hair was digested based on combustion reaction to obtain compatible solutions with ICP-MS analysis. Using microwave-induced combustion (MIC), masses of human hair ranging from 50 to 300 mg were efficiently digested. Only a diluted alkaline solution (100 mmol L-1 NH4OH) was used for the absorption of both analytes, which was fully compatible with ICP-MS analysis. Using these conditions low limits of detection were obtained (LOD of 0.01 µg g-1 for Br and 0.004 µg g-1 for I). Recovery tests at two levels (50% and 100%) using a standard solution or mixtures of the sample with certified reference materials (CRMs) were carried out to evaluate the suitability of proposed method and recoveries between 94% and 102% were always obtained. Accuracy was evaluated by analysis of a human hair CRM, and the Br and I concentrations obtained by the proposed method did not differ significantly from those described in the certificate. Repeatability (RSDs ≤ 4%) and reproducibility (RSDs ≤ 7%) of the results using proposed method were always very suitable. The digests obtained using the MIC method were fully compatible with ICP-MS and the interferences currently found using conventional digestion methods were completely eliminated. Ultra-trace concentrations of Br and I were determined in human hair, demonstrating that the proposed method is a suitable strategy, and it presents several advantages compared to others published in the literature.

7-chloro-4-(phenylselanyl) quinoline prevents dopamine depletion in a Drosophila melanogaster model of Parkinson's-like disease.

Neurodegeneration in Parkinson's disease appears to be caused by multiple factors, including oxidative damage and an increase in acetylcholinesterase expression that can culminate in loss of dopaminergic neurons. A selenium-containing quinoline derivative, 7-chloro-4-(phenylselanyl) quinoline (4-PSQ), shows important pharmacological actions mainly attributed to its antioxidant and anticholinesterase properties. Thus, this study investigated the neuroprotective effect of 4-PSQ in a model of Parkinson's-like disease induced by rotenone (ROT) in Drosophila melanogaster and verified whether these effects are related to selenium levels. Adult flies were divided into: [1] control, [2] 4-PSQ (25 µM), [3] ROT (500 µM), and [4] 4-PSQ (25 µM) + ROT (500 µM) groups and exposed to a diet containing ROT and/or 4-PSQ for 7 days, according to their respective groups. Survival, behavioral, and ex vivo analyses were performed. Dopamine levels, reactive species levels (RS), lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) activity, and proteic thiol (PSH) and non-proteic thiol (NPSH) content in the head region were analyzed, while acetylcholinesterase (AChE) activity and selenium levels in the head and body regions were analyzed. 4-PSQ was able to reverse the ROT-induced deficits in flies, reestablish dopamine and selenium levels, reverse cholinergic deficits, improve motor function, and ameliorate mortality. Furthermore, 4-PSQ also reduced RS levels and LPO, and restored the activities of the antioxidant enzymes, SOD and CAT. Interestingly, a positive relationship between dopamine and selenium levels could be seen. Our results demonstrate the neuroprotective effect of 4-PSQ, and we suggest that the compound may act via different mechanisms, such as improving antioxidant defenses and consequently reducing oxidative damages, as well as having an anticholinesterase action, which together can prevent dopamine depletion, as these actions were correlated with the presence of selenium in the 4-PSQ molecule.