Mancozeb (MZ), a manganese- and zinc-containing ethylene-bis-dithiocarbamate, is a broad-spectrum fungicide. Harmful effects of this fungicide have been reported in nontarget organisms via a not fully understood mechanism. Drosophila melanogaster has provided remarkable contributions for toxicological studies. This work was aimed at evaluating the biochemical targets and implication of oxidative stress in MZ-mediated toxicity in drosophilas. Exposure of flies for fifteen days to MZ at 5 and 10 mg/mL through the diet impaired locomotor performance and induced fly mortality. In parallel, it caused lipid peroxidation and reactive oxygen species (ROS) formation and Mn overload. MZ inhibited superoxide dismutase and inducted catalase and glutathione S-transferase activities. Nitric oxide and reduced glutathione levels were significantly decreased by MZ. Heat shock proteins (HSP70 and HSP83) and Nrf2 mRNA levels were significantly augmented in MZ-exposed flies. Our study reinforced the use of Drosophila melanogaster as a reliable model for the study of biochemical targets of pesticides, and based on our data, MZ induced oxidative damage and Mn accumulation in a concentration-dependent manner. An adaptative cellular state was inducted by the lower concentration of pesticide, possibly contributing to the slighter damage observed.

Taking together, these results suggest that the antiulcer activity of CCRE is dependent of NO and prostaglandin pathways possibly due to its ability to stimulate the synthesis of NO, and activation of endogenous prostaglandin production. Therefore, the use of CCRE in traditional Brazilian medicine against gastric disorders has a scientific basis.

Duguetia furfuracea is frequently used as a medicinal plant in Brazil. However, studies have evidenced its cytotoxic, bactericide, and antitumor activities. In the present study we aimed to evaluate the potential toxicity of hydroalcoholic leaves extracts of D. furfuracea (HEDF) in a Drosophila melanogaster model. Toxicity was assessed as changes in locomotor performance, mitochondrial activity, oxidative stress, MAPKs phosphorylation, and apoptosis induction after exposure to HEDF concentrations (1–50 mg/mL) for 7 days. The phytoconstituents of the plant were screened for the presence of alkaloids, tannins, xanthones, chalcones, flavonoids, aurones, and phenolic acids. Exposure of adult flies to HEDF caused mitochondrial dysfunction, overproduction of ROS, and alterations in the activity of detoxifying enzymes GST, SOD and CAT. Induction of ERK phosphorylation and PARP cleavage was also observed, indicating occurrence of HEDF-induced cell stress and apoptotic cell death. In parallel, alterations in cholinesterase activity and impairments in negative geotaxis behavior were observed. Our study draws attention to the indiscriminate use of this plant by population and suggests oxidative stress as a major mechanism underlying its toxicity.

Context: Croton campestris A.St.-Hil. (Euphorbiaceae) is a species native to Northeast Brazil used by traditional communities for the treatment of a variety of health problems. However, potential toxicological effects of this plant are unknown. Objective: The potential toxicity of the hydroalcoholic extract of C. campestris leaves on Drosophila melanogaster insect model, additionally with phytochemical constitution and cellular mechanisms mediating the action of extract were analysed in this study. Materials and methods: Constituents of the extract were evaluated by HPLC. In vitro antioxidant potential of extract was analysed by DPPH, ABTS and FRAP. Flies injected culture medium mixed with extract (0.1-50 mg/mL) for 72 h. After, ROS production was evaluated by DCF-DA oxidation. Phosphorylation of MAPK signalling pathway was investigated by Western blotting method. Activity of antioxidant enzymes was analysed in homogenates.Results: Major components of the extract include quercetin (38.11 ± 0.06 mg/g), caffeic acid (20.06 ± 0.17 mg/g) and kaempferol (15.45 ± 0.05 mg/g). Consumption of the extract impaired locomotor performance and induced fly death of flies (LC 50 of 26.51 mg/mL). Augmented ROS formation and SOD, CAT and GST activity were observed from 0.1 mg/mL. JNK and p38 kinases phosphorylation was modulated and Paraquat-induced toxicity was augmented by extract. Discussion and conclusion: Our data show important toxicological effects of C. campestris leading to increased mortality and impaired locomotor performance accompanied by induction of cell stress markers in flies. The study draws attention to the indiscriminate use of plant extracts. ARTICLE HISTORY

RESUMOO fruto Anacardium microcarpum é encontra em vários biomas da região NE do Brasil, seu fruto possui altos teores de vitamina C, açúcares, compostos fenólicos e minerais (cálcio, ferro e fósforo). Estudos prévios demonstraram o potencial biológico do suco de caju, dentre estes potencial antitumoral atribuído ao ácido anacárdico. Desta forma, o presente trabalho tem como objetivo avaliar a toxicidade e neuroproteção do extrato liofilizado de A. microcarpum em Drosophila Melanogaster no modelo de parkinsonismo induzido pelo inseticida Paraquat. Avaliaram-se a taxa de mortalidade, atividade locomotora, potencial citotóxico e a atividade antioxidante. Este estudo demonstra a baixa toxicidade in vivo do extrato do cajuizeiro, e seu potencial neuroprotetor no modelo de parkinsonismo em D. melanogaster, tal efeito pode estar associado em partes à ação antioxidante da planta. Este estudo ressalta o potencial biológico do cajuizeiro como um possível agente terapêutico em modelos de doenças neurodegenerativas, aliado a sua baixa toxicidade. Palavras-chave:Anacardium microcarpum, antioxidante, estresse oxidativo, neuroproteção, Parkinson e doenças neurodegenerativas. INTRODUÇÃOA Doença ou Mal de Parkinson (DP) é uma doença neurológica degenerativa progressiva do sistema nervoso central que atinge principalmente o sistema motor. Acredita-se que a geração de espécies reativas de oxigênio em condições de estresse oxidativo possui importante papel na causa da doença neurodegenerativa e na progressão da DP 1 . Nesse sentido, os antioxidantes destacam-se por prevenir a formação e a ação das espécies reativas de oxigênio e nitrogênio que se associam ao dano oxidativo 2 .