A candidate short-term toxicity test using Ampelisca brevicornis to assess sublethal responses to pharmaceuticals bound to marine sediments

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

A conjugate of the lytic peptide Hecate and gallic acid: structure, activity against cervical cancer, and toxicity

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Determination of estrogenic mycotoxins in environmental water samples by low-toxicity dispersive liquid-liquid microextraction and liquid chromatography-tandem mass spectrometry

A novel, simple, rapid and eco-friendly method based on dispersive liquid-liquid microextraction using a bromosolvent was developed to determine six estrogenic mycotoxins (zearalenone, zearalanone, alpha-zearalanol, beta-zearalanol, alpha-zearalenol and beta-zearalenol) in water samples by liquid chromatography-electrospray ionization tandem mass spectrometry in the negative mode (LC-ESI-MS/MS). The optimal conditions for this method include the use of 100 mu L bromocyclohexane as an extraction solvent (using a non-dispersion solvent), 10 mL of aqueous sample (adjusted to pH 4), a vortex extraction time of 2 min, centrifugation for 10 min at 3500 rpm and no ionic strength adjustment. The calibration function was linear and was verified by applying the Mandel fitting test with a 95% confidence level. No matrix effect was observed. According to the relative standard deviations (RSDs), the precision was better than 13% for the repeatability and intermediate precision. The average recoveries of the spiked compounds ranged from 81 to 118%. The method limits of detection (LOD) and quantification (LOQ) considering a 125-fold pre-concentration step were 4-20 and 8-40 ng L-1, respectively. Next, the method was applied to the analysis of the environmental aqueous samples, demonstrating the presence of beta-zearalanol and zearalanone in the river water samples. (C) 2015 Elsevier B.V. All rights reserved.

Poloxamer-based binary hydrogels for delivering tramadol hydrochloride: sol-gel transition studies, dissolution-release kinetics, in vitro toxicity, and pharmacological evaluation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Use, development and improvements in the protocol of whole-sediment toxicity identification evaluation using benthic copepods

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Teflubenzuron as a tool for control of trichodinids in freshwater fish: Acute toxicity and in vivo efficacy

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Acute and subacute (28 days) oral toxicity assessment of the oil extracted from Acrocomia aculeata pulp in rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Surface engineering of silica nanoparticles for oral insulin delivery: characterization and cell toxicity studies

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Acute toxicity and determination of the active constituents of aqueous extract of uncaria tomentosa bark in hyphessobrycon eques

Uncaria tomentosa is a medicinal plant used in folk medicine by Amazon tribes. In this study the constituents of aqueous extract of U. tomentosa bark were quantified by chromatographic technique and its lethal concentration 50 (48 h) in Hyphessobrycon eques was determined. The chromatography showed high levels of oxindole alkaloids, quinovic acid glycosides, and low molecular weight polyphenols. The CL50 48 h was 1816 mg/L. Fish showed behavior changes at concentrations above 2000 mg/L, accompanied by a significant decrease of dissolved oxygen. At the highest concentration 100% mortality was observed attributed to oxygen reduction by the amount of oxindole alkaloids, polyphenols accumulation of the extract in the gills, and the interaction of these compounds with dopamine. In conclusion, the aqueous extract of U. tomentosa did not alter the chemical components and it was shown that U. tomentosa has low toxicity to H. eques; therefore, it can be used safely in this species.

Assessment of cytotoxicity and AhR-mediated toxicity in tropical fresh water sediments under the influence of an oil refinery

Oil refinery effluents contain many chemicals at variable concentrations. Therefore, it is difficult to predict potential effects on the environment. The Atibaia River (SP, Brazil), which serves as a source of water supply for many municipalities, receives the effluents of one of the biggest oil refinery of this country. The aim of this study was to identify the (eco)toxicity of fresh water sediments under the influence of this oil refinery through neutral red (cytotoxicity) and ethoxyresorufin-O-deethylase (EROD) assays (AhR-mediated toxicity) in RTL-W1 cells (derived from fish liver). Once the refinery captures the waters of Jaguarí River for the development of its activities and discharges its effluents after treatment into the Atibaia River, which then flows into Piracicaba River, sediments from both river systems were also investigated. The samples showed a high cytotoxic potential, even when compared to well-known pollution sites. However, the cytotoxicity of samples collected downstream the effluent was not higher than that of sediments collected upstream, which suggested that the refinery discharges are not the main source of pollution in those areas. No EROD activity could be recorded, which could be confirmed by chemical analyses of polycyclic aromatic hydrocarbons (PAHs) that revealed a high concentration of phenanthrene, anthracene, fluoranthene, and pyrene, which are not EROD inducers in RTL-W1 cells. In contrast, high concentrations of PAHs were found upstream the refinery effluent, corroborating cytotoxicity results from the neutral red assay. A decrease of PAHs was recorded from upstream to downstream the refinery effluent, probably due to dilution of compounds following water discharges. On the other hand, these discharges apparently contribute specifically to the amount of anthracene in the river, since an increase of anthracene concentrations could be recorded downstream the effluent. Since the extrapolation of results from acute toxicity to specific toxic effects with different modes of action is a complex task, complementary bioassays covering additional specific effects should be applied in future studies for better understanding of the overall ecotoxicity of those environments.

Lack of reproductive toxicity in adult male rats exposed to interferon-alpha

Interferon-alpha (IFN- α ), a type I IFN, is a protein with antiviral, antiproliferative, and immunoregulatory activities, widely used in the treatment of several types of cancers as well as hepatitis B and C. Decrease of libido and erectile dysfunction are commonly reported by male patients during treatment of chronic hepatitis C with IFN- α . However, IFN therapy-associated underlying factors attributed to sexual dysfunction are still not well defined. Currently, there are few studies investigating the effects of IFN on male reproductive system functions. Given that, the aim of the present investigation was to examine effects of subchronic exposure to IFN- α (5 × 10(4) U/kg and 10 × 10(4) U/kg, 30 d) on serum hormones, sperm parameters, fertility, and testicular and epididymal hystopathology and morphometry in adult male Wistar rats. None of the evaluated parameters was markedly altered by IFN- α . Thus, our results suggest that exposure to IFN- α , in this experimental design, did not adversely affect sperm quality and fertile capacity of male rats.

Evaluation of the anti-mycobacterium tuberculosis activity and in vivo acute toxicity of annona sylvatic

Background The recent emergence of extensively multidrug-resistant Mycobacterium tuberculosis strains has further complicated the control of tuberculosis. There is an urgent need for the development of new molecular candidates antitubercular drugs. Medicinal plants have been an excellent source of leads for the development of drugs. The aim of this study was to evaluate the in vitro activity of 28 alcoholic extracts and essential oils of native and exotic Brazilian plants against Mycobacterium tuberculosis and to further study these extracts through chemical fractionation, the isolation of their constituents, and an evaluation of the in vivo acute toxicity of the active extracts. To the best of our knowledge this is the first chemical characterization, antituberculosis activity and acute toxicity evaluation of Annona sylvatica. Methods The anti-mycobacterial activity of these extracts and their constituent compounds was evaluated using the resazurin reduction microtiter assay (REMA). To investigate the acute toxicity of these extracts in vivo, female Swiss mice were treated with the extracts at doses of 500, 1000 and 2000 mg · kg-1 of body weight. The extracts were characterized by LC-MS, and the constituents were isolated and identified by chromatographic analysis of spectroscopic data. Results Of the 28 extracts, the methanol extract obtained from the leaves of Annona sylvatica showed anti-mycobacterial activity with an minimal inhibitory concentration (MIC) of 184.33 μg/mL, and the ethyl acetate fraction (EAF) resulting from liquid-liquid partitioning of the A. sylvatica extract showed an MIC of 115.2 μg/mL. The characterization of this extract by LC-MS identified flavonoids and acetogenins as its main constituents. The phytochemical study of the A. sylvatica EAF resulted in the isolation of quercetin, luteolin, and almunequin. Conclusions Among the compounds isolated from the EAF, luteolin and almunequin were the most promising, with MICs of 236.8 μg/mL (827.28 μM) and 209.9 μg/mL (328.48 μM), respectively. The acute administration of the EAF fraction in doses of 500, 1000, and 2000 mg · kg-1 of body weight did not cause signs of toxicity in the treated animals.

Toxicity and loss of mitochondrial membrane potential induced by Alkyl Gallates in Trypanosoma cruzi

American trypanosomiasis or Chagas disease is a debilitating disease representing an important social problem that affects, approximately, 10 million people in the world. The main aggravating factor of this situation is the lack of an effective drug to treat the different stages of this disease. In this context, the search for trypanocidal substances isolated from plants, synthetic or semi synthetic molecules, is an important strategy. Here, the trypanocidal potential of gallates was assayed in epimastigotes forms of T. cruzi and also, the interference of these substances on the mitochondrial membrane potential of the parasites was assessed, allowing the study of the mechanism of action of the gallates in the T. cruzi organisms. Regarding the preliminary structure-activity relationships, the side chain length of gallates plays crucial role for activity. Nonyl, decyl, undecyl, and dodecyl gallates showed potent antitrypanosomal effect (IC50 from 1.46 to 2.90 μM) in contrast with benznidazole (IC50 = 34.0 μM). Heptyl gallate showed a strong synergistic activity with benznidazole, reducing by 105-fold the IC50 of benznidazole. Loss of mitochondrial membrane potential induced by these esters was revealed. Tetradecyl gallate induced a loss of 53% of the mitochondrial membrane potential, at IC50 value.

Subacute toxicity assessment of diflubenzuron, an insect growth regulator, in adult male rats

Difubenzuron (DFB), an insecticide and acaricide insect growth regulator, can be used in agriculture against insect predators and in public health programs, to control insects and vectors, mainly Aedes aegypti larvae. Due to the lack of toxicological assessments of this compound, the objective of the present study was to evaluate the toxicological effects of subacute exposure to the DFB insecticide in adult male rats. Adult male rats were exposed (gavage) to 0, 2, 4, or 8 mg/kg of DFB for 28 days. No clinical signs of toxicity were observed in the DFB-treated animals of the experimental groups. However, there was an increase in serum levels of alanine aminotransferase in the group that received 8 mg/Kg/DFB/day and urea at doses of 4 and 8 mg/Kg/DFB/day, without altering other biochemical or hematological parameters. The subacute exposure to the lowest dose of DFB caused significant decrease in testis weight, daily sperm production, and in number of sperm in the epididymis in relation to the control group. However, no alterations were observed in the sperm morphology, testicular, epididymis, liver and kindney histology, or testosterone levels. These findings unveiled the hazardous effects of DFB on male reproduction after the subacute exposure and special attention should be addressed to the effects of low doses of this pesticide.