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Cadmium (Cd) and zinc (Zn) toxicity causes physiological disorders and harms plants, interfering with the rehabilitation of areas affected by mining activities. This study evaluated how the exposure to Zn and/or Cd affects the growth of native andropogon grass (Andropogon gayanus Kunth) plants originally found in areas contaminated with Cd and/or Zn due to zinc mining activities. Plants were cultivated for 7 weeks in a nutrient solution treated with Zn (142.3-854.0 μM) or Cd (0.9-13.3 μM) separately or combined with a molar ratio of 64:1 (Zn:Cd). A control treatment was grown in a complete Hoagland and Arnon solution (without Cd). Plant height, stem diameter, internode length, dry weight, Cd and Zn concentration, and accumulation in shoots/roots, as well as ultrastructure of roots and leaves were analyzed at the end of the experiment. The root dry weight was not significantly affected by the addition of the metals. Moreover, Zn provided higher shoot dry weight (up to 160%) relative to control. Andropogon grass tolerated both metals better separately than when applied together. Transmission electron microscopy analyses showed modifications such as vesiculation and vacuolation in the ultrastructure of andropogon tissues by Cd and/or Zn. The andropogon grass was tolerant to the doses tested, evidencing that it has potential for recovering areas contaminated with Zn and/or Cd.

Cancer treatment is challenging, mainly due to high levels of drug toxicity and the resistance of tumours to chemotherapy. Hydroxamic acid derivatives have recently aroused attention due to their potential to treat malignancies. In the present study, we sought to investigate the anticancer effects of a new series of synthetic acetohydroxamates. The in vitro cytotoxic and antiproliferative effects of 11 synthetic acetohydroxamates were evaluated against the melanoma cell line A375. Apoptosis, cell cycle, and autophagy assays were employed to elucidate the cell death pathways induced by the compounds. The in vivo pharmacokinetic profiles of the most promising compounds were determined in CD-1 mice, while the in vivo antitumour efficacies were evaluated using the A375 melanoma xenograft model in nude mice. MTT assays revealed that all compounds presented concentration-dependent cytotoxicity against the A375 cell line. AKS 61 produced the most favourable antiproliferative activity according to the sulphorhodamine B and clonogenic assays. AKS 61 treatment resulted in decreased mitochondrial membrane potential and increased apoptosis and autophagy in the A375 cell line. However, AKS 61 failed to prevent in vivo tumour growth in a melanoma xenograft, whereas compound AKS 7 was able to inhibit tumour growth when administered orally. These in vivo findings may be explained by a more favourable pharmacokinetic profile presented by AKS 7 when compared to AKS 61. Taken together, these results suggest that acetohydroxamates have potential anticancer effects and will guide future optimisation of these molecules to allow for further non-clinical development.

Rotenone exposure in rodents provides an interesting model for studying mechanisms of toxin-induced dopaminergic neuronal injury. However, several aspects remain unclear regarding the effects and the accuracy of rotenone as an animal model of Parkinson's disease (PD). In order to counteract these limitations, this study characterized a precise neurotoxin-delivery strategy employing the bilateral intranigral administration protocol of rotenone as a reliable model of PD. We performed bilateral intranigral injections of rotenone (12 μg) and subsequent general activity (1, 10, 20, and 30 days after rotenone) and cognitive (7, 8, 15, and 30 days after rotenone) evaluations followed by neurochemical and immunohistochemical tests. We have observed that rotenone was able to produce a remarkable reduction on the percentage of tyrosine hydroxylase immunoreactive neurons (about 60%) within the substantia nigra pars compacta. Dopamine (DA) was severely depleted at 30 days after rotenone administration, similarly to its metabolites. In addition, an increase in DA turnover was detected at the same time-point. In parallel, striatal serotonin and its metabolite were found to be increased 30 days after the neurotoxic insult, without apparent modification in the serotonin turnover. Besides, motor behavior was impaired, mainly 1 day after rotenone. Furthermore, learning and memory processes were severely disrupted in different time-points, particularly at the training and test session (30 days). We now provide further evidence of a time-dependent neurodegeneration associated to cognitive impairment after the single bilateral intranigral administration of rotenone. Thus, it is proposed that the current rotenone protocol provides an improvement regarding the existing rotenone models of PD.