Variação em biomarcadores bioquímicos de contaminação em Tilápias do Nilo (Oreochromis niloticus) de diferentes portes

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

Estudo do efeito de metais em esterases de zebrafish (Danio rerio)

Pós-graduação em Química - IBILCE

Avaliação de neurotoxicidade de formas enantioméricas de praguicidas organifosforados: estudos in vitro, in vivo e de neuroproteção

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

Identificação dos inibidores de acetilcolinesterase em Tetrapterys mucronata Cav. (Malpighiaceae) e comparação quali e quantitativa dos derivados triptamícos presentes na espécie em estudo e Ayahuasca

Pós-graduação em Química - IQ

Degradation, residual determination, and cholinesterase activity of triclorfon in Piaractus mesopotamicus Holmberg (Pacu) 1887

The aim of this study was to determine the no-observable-adverse-effect concentration (NOAEC) for trichlorfon, an antiparasitic agent used in aquaculture, in Piractus mesopotamicus (pacu) using acetylcholinesterase (AChE) activity as an end point. Fish were exposed 24 h/d for 15 d to different concentrations of trichlorfon in tanks of water for which a curve of dissipation was previously determined. Analysis of trichlorfon in water and fish plasma using gas chromatography with electron capture detection (GC-ECD) enabled measurement of limit of detection (LOD) and limit of quantification (LOQ), respectively, to be 3 and 10 ppb. Thirty-six hours after trichlorfon dilution in water, the concentration was below the LOD, and data showed that plasma concentrations did not exceed the LOQ. Apart from the 6.25 g/L, all concentrations of trichlorfon significantly inhibited plasma and brain AChE activity compared to controls. The AChE activity levels returned to control values in 7 d. These data may be useful to determine the concentration of trichlorfon that destroys parasites without producing adverse effects in fish.

Antifungal Compounds Produced by Colletotrichum gloeosporioides, an Endophytic Fungus from Michelia champaca

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

Effect of mixture of diazinon and benzo[a]pyrene in Glutathione S-transferase of Nile tilapia

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

Avaliação dos efeitos de concentrações subletais de dimetoato no cérebro e ventrículo de Apis mellifera africanizada

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Atrazine levels in the Jaboticabal water stream (Sao Paulo State, Brazil) and its toxicological effects on the pacu fish Piaractus mesopotamicus

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Metabolic effects of trichlorfon (Masoten (R)) on the neotropical freshwater fish pacu (Piaractus mesopotamicus)

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

Avaliação bioquímica e imunohistoquímica dos efeitos subletais do tiametoxam sobre Apis mellifera (Hymenoptera, Apidae)

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

Influência da temperatura nas respostas aos biocidas diazinon e carbaril em Dilocarcinus pagei Stimpson, 1861

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effects of a cyanobacterial extract containing-anatoxin-a(s) on the cardiac rhythm of Leurolestes circunvagans

This work presents the effects of an anatoxin-a(s)-containing extract on a cockroach semi-isolated heart preparation and the results supporting the extract s biological activity on acetylcholinesterase (purified from ell). The presence of the toxin in cyanobacterial strains Anabaena spiroides (ITEP-024, ITEP-025 and ITEP-026) isolated from the Tapacurá reservoir in Pernambuco, Brazil, was confirmed by means of liquid chromatography coupled to an ion-trap mass spectrometer. The anticholinesterase activity was assessed biochemically by the Ellman test and was confirmed by measuring the cockroach s heart rate. The concentration of the extract containing the tested anatoxin-a(s) (antx-a(s)) (10, 16 and 100 μg.μL-1) inhibited the eel acetylcholinesterase (AChE) by more than 90%. The cockroach cardiac frequency increased by a maximum of about 20% within 29 min after the addition of 2.5x10³ μg of extract containing antxa (s).g-1 bw (n=9, p<0.05). Our results strongly indicate that antx-a(s) is capable of exerting biological effects on cockroach, indicating that more research might be conducted to determine its role in the environment, especially on insects.

New Synthetic Polyamines as Multi-Target-Directed Ligands for the Treatment of Alzheimer's Disease and Cancer: Design, Synthesis and Biological Evaluation

Alzheimer's disease (AD) and cancer represent two of the main causes of death worldwide. They are complex multifactorial diseases and several biochemical targets have been recognized to play a fundamental role in their development. Basing on their complex nature, a promising therapeutical approach could be represented by the so-called "Multi-Target-Directed Ligand" approach. This new strategy is based on the assumption that a single molecule could hit several targets responsible for the onset and/or progression of the pathology. In particular in AD, most currently prescribed drugs aim to increase the level of acetylcholine in the brain by inhibiting the enzyme acetylcholinesterase (AChE). However, clinical experience shows that AChE inhibition is a palliative treatment, and the simple modulation of a single target does not address AD aetiology. Research into newer and more potent anti-AD agents is thus focused on compounds whose properties go beyond AChE inhibition (such as inhibition of the enzyme β-secretase and inhibition of the aggregation of beta-amyloid). Therefore, the MTDL strategy seems a more appropriate approach for addressing the complexity of AD and may provide new drugs for tackling its multifactorial nature. In this thesis, it is described the design of new MTDLs able to tackle the multifactorial nature of AD. Such new MTDLs designed are less flexible analogues of Caproctamine, one of the first MTDL owing biological properties useful for the AD treatment. These new compounds are able to inhibit the enzymes AChE, beta-secretase and to inhibit both AChE-induced and self-induced beta-amyloid aggregation. In particular, the most potent compound of the series is able to inhibit AChE in subnanomolar range, to inhibit β-secretase in micromolar concentration and to inhibit both AChE-induced and self-induced beta-amyloid aggregation in micromolar concentration. Cancer, as AD, is a very complex pathology and many different therapeutical approaches are currently use for the treatment of such pathology. However, due to its multifactorial nature the MTDL approach could be, in principle, apply also to this pathology. Aim of this thesis has been the development of new molecules owing different structural motifs able to simultaneously interact with some of the multitude of targets responsible for the pathology. The designed compounds displayed cytotoxic activity in different cancer cell lines. In particular, the most potent compounds of the series have been further evaluated and they were able to bind DNA resulting 100-fold more potent than the reference compound Mitonafide. Furthermore, these compounds were able to trigger apoptosis through caspases activation and to inhibit PIN1 (preliminary result). This last protein is a very promising target because it is overexpressed in many human cancers, it functions as critical catalyst for multiple oncogenic pathways and in several cancer cell lines depletion of PIN1 determines arrest of mitosis followed by apoptosis induction. In conclusion, this study may represent a promising starting pint for the development of new MTDLs hopefully useful for cancer and AD treatment.

Effect of oral donepezil on intraocular pressure in normotensive Alzheimer patients

Donepezil, a selective acetylcholinesterase (AChE) inhibitor, has been shown to reduce intraocular pressure (IOP) in ocular normotensive rabbit eyes. The aim of this investigation was to evaluate the effect of oral donepezil on IOP and pupil diameter after mid-term oral treatment in normotensive persons. Thirty-two newly diagnosed Alzheimer patients with normal IOP and no further antiglaucomatous treatment were included in the study. IOP and pupil diameter were evaluated before and 4 weeks after daily intake of 5 mg donepezil. IOP and pupil diameter were significantly lower/smaller after 4 weeks of treatment. The mean IOP of all 63 eyes was 14.1 mmHg before and 12.8 mmHg after treatment (8.8% reduction). Mean pupil diameter constricted from 3.9 to 3.6 mm (-7.4%). These findings show that donepezil, and, possibly, other selective AChE inhibitors, can potentially be used to treat glaucoma. They are also known to have neuroprotective effects in Alzheimer's, and, therefore, might have an additional therapeutic benefit.