Assessment of the neurotoxic potential and acute toxicity of copaiba

O óleo-resina de copaíba obtido do gênero Copaifera L., Fabaceae, é largamente utilizado na medicina popular como antiinflamatório, antimicrobiano e antitumoral. Porém, informações sobre seu potencial tóxico são escassos na literatura. O objetivo deste estudo foi estabelecer a toxicidade oral aguda e os possíveis efeitos neurotóxicos relacionados à ingestão do óleo-resina de Copaifera reticulata Ducke, Fabaceae, em ratas Wistar. O estudo foi conduzido com quinze ratas nulíparas distribuídas nos grupos de doses 300 e 2000 mg/kg pc de óleo-resina administrado por gavagem. Os resultados obtidos mostraram que nestas doses não houve sinais clínicos de toxicidade ou neurotoxicidade, alteração no consumo de ração ou alteração no peso corpóreo. A dose letal aguda foi estimada como maior que 2000 mg/kg pc e classificada como categoria 5, segundo o Guia OECD 423. Estes resultados indicam que existe uma relativa margem de segurança para o uso do óleo-resina de copaíba como agente terapêutico, embora estudos toxicológicos adicionais sejam ainda necessários, principalmente com a administração repetida de baixas doses.Copaiba oil-resin obtained from Copaifera L. genus, Fabaceae, is largely used in popular medicine as antinflammatory, antimicrobial and antitumoral. Information concerning the potential toxicity of this oil is limited in the literature. The goal of this study was to investigate the acute toxicity and the possible neurotoxic effects related to the ingestion of Copaifera reticulata Ducke, Fabaceae, oil-resin using female Wistar rats. Fifteen nulliparous rats were used and distributed in the experimental groups orally exposed to doses of 300 e 2000 mg/kg bw of oil-resin (gavage). No overt clinical signs of toxicity or neurotoxicity, alteration of food consumption or body weight were observed in the animals at the tested doses. The lethal oral toxicity was estimated to be higher than 2000 mg/kg bw, classified as category 5 according to OECD Guide 423. These results indicate that there is a certain safety margin associated with the use of copaiba as therapeutic agent, although additional toxicological studies are still necessary, mainly using repeated low doses

HPLC-FLD method for itraconazole quantification in poly lactic-co-glycolic acid nanoparticles, plasma and tissue

Itraconazol, um antifúngico de amplo espectro, possui muitos efeitos colaterais e o uso de nanossistemas para a entrega de fármacos tem sido proposto como um método para otimizar a farmacocinética da droga e reduzir os efeitos colaterais. Um procedimento de cromatografia líquida de alta performance (HPLC) utilizando detecção fluorimétrica foi desenvolvido para a determinação de itraconazol em nanopartículas do copolímero de ácido láctico e glicólico, plasma e tecidos. A linearidade, limites de detecção e quantificação, recuperação, precisão, seletividade e estabilidade do método foram estabelecidas. O método desenvolvido foi testado na detecção e quantificação de itraconazol na biodistribuição de nanopartículas administrados intraperitonealmente em camundongos fêmeas Balb/C. Neste estudo foi desenvolvido um método analítico de HPLC com detecção fluorimétrica para quantificação de itraconazole em nanopartículas poliméricas, tecidos e plasma, sendo ele sensível, de baixo custo, viável para uso de rotina e com potencial para aplicação na biodistribuição e estudos farmacocinéticos de itraconazole em nanossistemas.Itraconazole, a broad-spectrum anti-fungal, has many side effects, and nanosystems for drug delivery have been proposed as a method to optimize the drug's pharmacokinetics and reduce side effects. An high performance liquid chromatography (HPLC) procedure using fluorometric detection was developed for determination of itraconazole in polymeric poly(lactic-co-glycolic acid) nanoparticles, plasma and tissue. Linearity, limits of detection and quantification, recovery, precision, selectivity and stability were established. The developed method was tested in itraconazole detection and quantification of biodistribution of nanoparticles administered intraperitoneally to Balb/C female mice. This study developed an analytical method for HPLC with fluorometric detection for quantification of itraconazole in polymeric nanoparticles, tissue and plasma, which is sensitive, low cost, viable for routine usage and with potential for application in itraconazole biodistribution and pharmacokinetics studies

Evaluation of the Genotoxic and Antigenotoxic Effects of Andiroba ( Carapa guianensis

The Carapa guianensis (andiroba) oil is commonly used by the Amazon population for medicinal purposes. The objective of this study was to determine the genotoxic and antigenotoxic potential of the andiroba oil (AO) and nanoemulsion (AN) using Swiss mice. Therefore, we used the comet assay and micronucleus test. The AO predominant compounds were oleic (39.13%), palmitic (33.22%), and linoleic (16.86%) acids. AN composition obeyed the surfactant/oil ratio of 0.69, and the Tween 80/Span 80 ratio was held at 0.9. Our results showed no cytotoxicity or genotoxicity in the mice treated with AO and AN alone. However, there was a significant reduction in the polychromatic erythrocytes (PCEs) numbers in all groups treated with doxorubicin (DOX), including those pretreated with AO and AN. Thus, the samples tested did not protect against DOX. On the other hand, our results showed a large increase in micronucleus (MN) formation when the mice were treated with DOX alone; these numbers were reduced when the animals were pretreated with AO and AN. The results indicate a protective effect of andiroba on MN formation and show no evidence of genotoxicity in mice

Comet and cytogenetic tests as tools for evaluating genomic instability in seeds of Oryza sativa L. and Phaseolus vulgaris L. from gene banks

This study aimed to assess the feasibility of comet and cytogenetic tests as tools for evaluating genomic instability in seeds of Oryza sativa L. (rice) and Phaseolus vulgaris (beans) L. from gene banks. Rice and beans were exposed to methyl methanesulfonate (MMS) as a reference DNA damaging agent. Seeds of two accessions of rice and beans were obtained from Embrapa Rice and Beans - Brazil. Seed groups were imbibed in three concentrations of MMS for three periods of time to carry out cytogenetic tests, and for one period for the comet test. At concentrations of 10 and 15 mg/L, MMS induced cytotoxic and/or mutagenic effects in the meristematic cells of roots from all the accessions of both species. In the comet test, MMS induced genotoxic effects at all the concentrations in the evaluated accessions of rice and beans, except in one accession of beans at the lowest concentration (5 mg/L). Both species showed sensitivity to MMS. The comet test can be proposed for the measurement of genomic instability in accessions of rice and beans in gene banks, as being more sensitive than the cytogenetic tests used

Experimental Investigation of the Coprecipitation Method: An Approach to Obtain Magnetite and Maghemite Nanoparticles with Improved Properties

Iron oxides that exhibit magnetic properties have been widely studied not only from an academic standpoint, but also for numerous applications in different fields of knowledge, such as biomedical and technological research. In this work, magnetite and maghemite nanoparticles were synthesized by chemical coprecipitation of FeCl2·4H2O and FeCl3·6H2O (proportion of 1 : 2) in three different cases using two bases (sodium hydroxide and hydroxide ammonium) as precipitants. The chemical coprecipitation method was selected for its simplicity, convenience, reproducibility, and low cost in the use of glassware. The nanostructured materials were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD) and magnetometry (VSM). The objective of this work is to study the variation in the morphological characteristics and physical properties of nanoparticles magnetic as a function of the different production processes. As observed by TEM, the materials obtained from the precipitating agent NH4OH are more uniform than those obtained with NaOH. From XRD pattern analysis, it appears that the obtained materials correspond to magnetite and maghemite and, from magnetometry VSM analysis, show high magnetization as a function of the magnetic field at room temperature, indicating that these materials are superparamagnetic

Exposure to tricyclic antidepressant nortriptyline affects early-life stages of zebrafish (Danio rerio)

Psychiatric drugs are among the leading medications prescribed for humans, with their presence in aquatic environments raising concerns relating to potentially harmful effects on non-target organisms. Nortriptyline (NTP) is a selective serotonin-norepinephrine reuptake inhibitor antidepressant, widely used in clinics and found in environmental water matrices. In this study, we evaluated the toxic effects of NTP on zebrafish (Danio rerio) embryos and early larval stages. Developmental and mortality analyses were performed on zebrafish exposed to NTP for 168 h at concentrations ranging from 500 to 46,900 µg/L. Locomotor behaviour and acetylcholinesterase (AChE) activity were evaluated by exposing embryos/larvae to lower NTP concentrations (0.006–500 µg/L). The median lethal NTP concentration after 168 h exposure was 2190 µg/L. Although we did not identify significant developmental changes in the treated groups, lack of equilibrium was already visible in surviving larvae exposed to ≥ 500 µg/L NTP. The behavioural analyses showed that NTP was capable of modifying zebrafish larvae swimming behaviour, even at extremely low (0.006 and 0.088 µg/L) environmentally relevant concentrations. We consistently observed a significant reduction in AChE activity in the animals exposed to 500 µg/L NTP. Our results highlight acute toxic effects of NTP on the early-life stages of zebrafish. Most importantly, exposure to environmentally relevant NTP concentrations may affect zebrafish larvae locomotor behaviour, which in turn could reduce the fitness of the species. More studies involving chronic exposure and sensitive endpoints are warranted to better understand the effect of NTP in a more realistic exposure scenario

Avaliação da toxicidade aguda e potencial neurotóxico do óleo-resina de copaíba (Copaifera reticulata Ducke, Fabaceae)

O óleo-resina de copaíba obtido do gênero Copaifera L., Fabaceae, é largamente utilizado na medicina popular como antiinflamatório, antimicrobiano e antitumoral. Porém, informações sobre seu potencial tóxico são escassos na literatura. O objetivo deste estudo foi estabelecer a toxicidade oral aguda e os possíveis efeitos neurotóxicos relacionados à ingestão do óleo-resina de Copaifera reticulata Ducke, Fabaceae, em ratas Wistar. O estudo foi conduzido com quinze ratas nulíparas distribuídas nos grupos de doses 300 e 2000 mg/kg pc de óleo-resina administrado por gavagem. Os resultados obtidos mostraram que nestas doses não houve sinais clínicos de toxicidade ou neurotoxicidade, alteração no consumo de ração ou alteração no peso corpóreo. A dose letal aguda foi estimada como maior que 2000 mg/kg pc e classificada como categoria 5, segundo o Guia OECD 423. Estes resultados indicam que existe uma relativa margem de segurança para o uso do óleo-resina de copaíba como agente terapêutico, embora estudos toxicológicos adicionais sejam ainda necessários, principalmente com a administração repetida de baixas doses

Multi-level toxicity assessment of the antidepressant venlafaxine in embryos/larvae and adults of zebrafish (Danio rerio)

Abstract The toxic effects of venlafaxine (VLX) on aquatic organisms have already been verified and therefore are a proven matter of concern. Herein, we evaluated zebrafish embryos/adults after acute exposure to VLX. Embryos/larvae were exposed to different concentrations of VLX (100-1000 mg/L; 1.33 as a dilution factor), to evaluate mortality/developmental changos and to analyze biomarkers (0.002-100 mg/L). For adults, mortality, genotoxicity, and biomarkers were assessed in five different concentrations of VLX (1-100 mg/L). The median lethal concentration (LC50-168h) was 274.1 mg/L for embryos/larvae, and >100 mg/L for adults (LC50-96h). VLX decreased the heart rate frequency and caused premature hatching and lack of equilibrium in embryos/larvae exposed to different concentrations ranging from 100 to 562.5 mg/L. The activity of acetylcholinesterase (AChE) was inhibited in larvae exposed to 1, 25 and 100 mg/L. Glutathione-S-transferase (GST) activity was reduced in both larvae and adults after exposure to different concentrations, mainly at 25 mg/L. For both larvae and adults, lactate dehydrogenase (LDH) activity increased after 100 mg/L of VLX exposure. No DNA damage was observed in peripheral erythrocytes. Exposure to VLX may cause adverse effects on zebrafish in their early and adult life stages, interfering with embryo-larval development, and can induce physiological disturbances in adults

Effects of AgNPs on the Snail Biomphalaria glabrata: Survival, Reproduction and Silver Accumulation

Silver nanoparticles (AgNPs) are used intensively in medical and industrial applications. Environmental concerns have arisen from the potential release of this material into aquatic ecosystems. The aims of this research were to evaluate the potential accumulation of silver in the whole body of organisms and analyze the effects of AgNPs on the survival and reproduction of the snail Biomphalaria glabrata. Results show slow acute toxicity with a 10-day LC50 of 18.57 mg/L and an effective decrease in the eggs and egg clutches per organism exposed to tested concentrations. Based on these data, the No Observed Effect Concentration (NOEC) observed was <1 mg/L for snail reproduction. For silver accumulation, we observed that uptake was faster than elimination, which was very slow and still incomplete 35 days after the end of the experiment. However, the observed accumulation was not connected with a concentration/response relationship, since the amount of silver was not equivalent to a higher reproductive effect. The data observed show that AgNPs are toxic to B. glabrata, and suggest that the snail has internal mechanisms to combat the presence of Ag in its body, ensuring survival and reduced reproduction and showing that the species seems to be a potential indicator for Ag presence in contaminated aquatic ecosystems