RESUMO
Human exposure to the natural environmental contaminant methylmercury (MeHg) has been associated to adverse health effects. Importantly, the mechanisms by which this organomercurial exerts its neurotoxicity have yet to be fully clarified. Therefore, the aim of this study was to evaluate whether exposure to MeHg alters dopamine (DA) and octopamine (OA) levels, acetylcholinesterase (AChE) activity and impacts both motor and non-motor behaviours. We studied the effect of MeHg by feeding 1-2 d old flies (male and females) with 25 and 50 µM MeHg for 4 d and determined effects on survival, motor and non-motor behaviours, oxidative stress, AChE and tyrosine hydroxylase (TH) activities, as well as DA and OA levels. We found that Drosophila melanogaster (D. melanogaster) exposed to MeHg showed a reduction in survival rate, associated with the inhibition of AChE and TH activities in head of flies and decreased DA and OA levels. These changes were accompanied by behavioural alterations, such as locomotor deficit and increased grooming behaviour, in addition to an increase in oxidative stress markers both in head and in body of flies, and an increase in glutathione-S-transferase (GST) activity in head of flies. Collectively, our data support the hypothesis that MeHg neurotoxicity is associated with altered OA and DA levels, AChE inhibition, which may serve, at least in part, as the underpinnings of both motor and non-motor behavioural changes.
Assuntos
Compostos de Metilmercúrio , Síndromes Neurotóxicas , Acetilcolinesterase/metabolismo , Animais , Colinérgicos/farmacologia , Dopamina , Drosophila melanogaster , Feminino , Humanos , Masculino , Compostos de Metilmercúrio/toxicidade , Estresse OxidativoRESUMO
Thimerosal (THIM) is a well-established antifungal and antiseptic agent widely used as a preservative in vaccines. Recent studies identified the neurotoxic effects of THIM, including malfunction of the monoaminergic system. However, the underlying cytotoxic mechanisms are not well understood. Here we used the fruit fly Drosophila melanogaster to investigate the mechanisms of THIM-induced neurotoxicity. We focused on the dopaminergic system, and the rate-limiting enzyme tyrosine hydroxylase (DmTyrH), to test the hypothesis that THIM can impair dopamine (DA) homeostasis and subsequently cause dysfunction. We studied the effect of THIM by feeding 1-2 day old flies (both sexes) food supplemented with 25 µM THIM for 4 days and determined THIM-induced effects on survival, oxidative stress, and metabolic activity based on MTT assay and acetylcholinesterase (AChE) activity. Our results demonstrate that D. melanogaster exposed to THIM present changes in DmTyrH expression and activity, together with altered DA levels that led to impaired motor behavior. These phenotypes were accompanied by an increase in oxidative stress, with a decrease in MTT reduction, in AChE activity, and also in survival rate. These findings suggest an initiating and primary role for THIM-mediated DmTyrH dysfunction that leads to impaired DA function and behavioral abnormalities, ultimately causing oxidative stress-related neurotoxicity.
Assuntos
Dopamina/metabolismo , Timerosal/farmacologia , Tirosina 3-Mono-Oxigenase/metabolismo , Animais , Drosophila melanogaster , Feminino , Glutationa Transferase/metabolismo , Masculino , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Tiorredoxina Dissulfeto Redutase/metabolismoRESUMO
Fly fruit Drosophila melanogaster (DM) has been extensively employed as an in vivo model system to study pesticides toxicity. Pesticide administration to the fly traditionally involves feeding in an agar-gelled feed fly's medium (AM). However, AM method has several limitations such as uncertainty regarding the bioavailability and amount of pesticides ingested. And also high manipulation of the treated flies. We developed a new method of exposure the flies to pesticides, called Continuous Liquid Feeding (CLF). This method successfully delivers food to the flies at much higher concentrations than the AM method, and requires little manipulation of flies under treatment.
Assuntos
Drosophila melanogaster/efeitos dos fármacos , Métodos de Alimentação , Praguicidas/toxicidade , Ágar/química , Animais , Drosophila melanogaster/fisiologia , Ingestão de Alimentos , Feminino , Glicina/análogos & derivados , Glicina/toxicidade , Locomoção/efeitos dos fármacos , Masculino , GlifosatoRESUMO
Extracts from the leaves of Bougainvillea glabra Choisy are used in traditional medicines, but their actions on the central nervous system have not been studied. In the present study, we investigated the potential neuroprotective effects of Bougainvillea glabra Choisy leaf extract (BG extract) against paraquat (PQ)-induced neurotoxicity. Male adult wild-type flies (1- 4days old) were exposed to PQ (3.5mM) and/or BG extract (120µg/mL) through food for 4days. PQ-fed flies had decreased locomotor capacity in negative geotaxis and crossing number assays and had a higher incidence of mortality than the control group. PQ neurotoxicity was also associated with a marked decrease in dopamine levels and increase in acetylcholinesterase (AChE) activity, reactive oxygen species (ROS) production and lipid peroxidation. Co-exposure to BG extract prevented mortality, and dopamine depletion, improved locomotor performance and decreased AChE activity, ROS production and lipid peroxidation. GC-MS and HPLC analyses of BG extract revealed the presence of many antioxidant compounds such as phytol, α,γ-tocopherol, squalene, stigmasterol, geranylgeraniol, quercetin, and caffeic, vanillic, coumaric, ferulic acids. Our results showed neuroprotective effects of BG extract, reflecting the presence of antioxidant compounds. Thus, we suggested that B. glabra leaves could be considered an effective agent in the prevention of neurological disorders, where dopamine depletion and/or oxidative stress are involved, as in Parkinson's disease (PD).