55 research outputs found
Sex differences on the feeding of the gobiid fish Bathygobius soporator in tide pools of Maiandeua Island, ParĂĄ, Brazil
Spatial, seasonal and ontogenetic changes in food resource use by a piscivore fish in two Pantanal lagoons, Brazil
Examination of the Cytotoxic and Embryotoxic Potential and Underlying Mechanisms of Next-Generation Synthetic Trioxolane and Tetraoxane Antimalarials
Semisynthetic artemisinin-based therapies are the first-line treatment for P. falciparum malaria, but next-generation synthetic drug candidates are urgently required to improve availability and respond to the emergence of artemisinin-resistant parasites. Artemisinins are embryotoxic in animal models and induce apoptosis in sensitive mammalian cells. Understanding the cytotoxic propensities of antimalarial drug candidates is crucial to their successful development and utilization. Here, we demonstrate that, similarly to the model artemisinin artesunate (ARS), a synthetic tetraoxane drug candidate (RKA182) and a trioxolane equivalent (FBEG100) induce embryotoxicity and depletion of primitive erythroblasts in a rodent model. We also show that RKA182, FBEG100 and ARS are cytotoxic toward a panel of established and primary human cell lines, with caspase-dependent apoptosis and caspase-independent necrosis underlying the induction of cell death. Although the toxic effects of RKA182 and FBEG100 proceed more rapidly and are relatively less cell-selective than that of ARS, all three compounds are shown to be dependent upon heme, iron and oxidative stress for their ability to induce cell death. However, in contrast to previously studied artemisinins, the toxicity of RKA182 and FBEG100 is shown to be independent of general chemical decomposition. Although tetraoxanes and trioxolanes have shown promise as next-generation antimalarials, the data described here indicate that adverse effects associated with artemisinins, including embryotoxicity, cannot be ruled out with these novel compounds, and a full understanding of their toxicological actions will be central to the continuing design and development of safe and effective drug candidates which could prove important in the fight against malaria
Habitat simplification affects nuclear-follower foraging association among stream fishes
Colonization of the CorumbĂĄ Reservoir (CorumbĂĄ River, ParanĂĄ River Basin, GoiĂĄs State, Brazil) by the "lambari" Astyanax altiparanae (Tetragonopterinae; Characidae)
Uso de recursos alimentares por peixes imaturos e adultos de espĂ©cies piscĂvoras em uma planĂcie de inundação neotropical
InfluĂȘncia do ambiente no conteĂșdo calĂłrico e na condição fisiolĂłgica de duas espĂ©cies migradoras de peixes neotropicais
Longitudinal use of feeding resources and distribution of fish trophic guilds in a coastal Atlantic stream, southern Brazil
Longitudinal gradient in limnological variables in the Upper ParanĂĄ River: a brief description and the importance of undammed tributaries
Anatomia Funcional e Morfometria do Intestino no Teleostei (Pisces) de Ăgua Doce Surubim (Pseudoplatystoma coruscans- Agassiz, 1829)
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