6^th Global Summit on Toxicology and Applied Pharmacology October 17-19, 2016 (10 Plenary Forums - 1 Event)
Houston, Texas, USA

Javier Del Pino received his PharmD degree at the University Complutense University of Madrid in 2004. He has two Masters in Sciences 2009 and 2010. He specialized in neurotoxicology and neurodevelopmental toxicology and received his PhD in Toxicology in 2009. In 2010 he worked in Institute of Health Carlos III in the National Center of Environmental Health. From 2010 to 2012 he was Associated Researcher at University of Massachusetts (UMASS) working in Sandra Petersen´s Lab in a National Institute of Health (NIH) project on developmental effects of TCDD endocrine disruptor on sexual differentiation. In 2016 he got a position as Associated Professor of Toxicology at the Complutense University of Madrid.

4-Aminopyridine (4-AP) is a potassium channel blocker used for the treatment of neuromuscular disorders. Otherwise, it has been described to produce a large number of adverse effects among them cell death mediated mainly by blockage of K+ channels. Specifically, 4-AP has been reported to produce cell death in central nervous system on hippocampal cells. However, a protective effect against cell death has also been described. On the other hand, Kv channel interacting protein 1 (KChIP1) is a neuronal calcium sensor protein that is predominantly expressed at GABAergic synapses and it has been related with modulation of K+ channels, GABAergic transmission and cell death. According to this KChIP1 could play a key role in the protective or toxic effects induced by 4-AP. We evaluated, in wild type and KChIP1 silenced primary hippocampal neurons, the effect of 4-AP (0.25 mM to 2 mM) with or without semicarbazide (0.3 M) co-treatment after 24 h and after 14 days 4-AP alone exposure on cell viability. 4-AP induced cell death after 24 h (from 1 mM) and after 14 days treatment, which was modulated by KChIP1 through GABAergic transmission. These data might help to explain protective and toxic effects observed after overdose and long term exposure.

Javier Del Pino received his PharmD degree at the University Complutense University of Madrid in 2004. He has two Masters in Sciences 2009 and 2010. He specialized in neurotoxicology and neurodevelopmental toxicology and received his PhD in Toxicology in 2009. In 2010 he worked in Institute of Health Carlos III in the National Center of Environmental Health. From 2010 to 2012 he was Associated Researcher at University of Massachusetts (UMASS) working in Sandra Petersen´s Lab in a National Institute of Health (NIH) project on developmental effects of TCDD endocrine disruptor on sexual differentiation. In 2016 he got a position as Associated Professor of Toxicology at the Complutense University of Madrid.

Chlorpyrifos (CPF) is an organophosphate insecticide reported to induce both after acute and repeated exposure learning and memory dysfunctions, although the mechanism is not completely known. CPF produces basal forebrain cholinergic neuronal loss, involved on learning and memory regulation, which could be the cause of such cognitive disorders. Otherwise, neuronal dendritic spines were reported to be also involved on learning and memory process regulation and their alteration could also contribute to this effect. In this regard, CPF has been reported to induce an alteration in the dendritic spines density in the prefrontal cortex and hippocampus after acute and repeated exposure to subclinical doses respectively, thus their alteration in basal forebrain cholinergic neurons could also mediate cognitive disorders. Accordingly, we hypothesized that CPF induces basal forebrain cholinergic dendritic spine alteration at low concentrations and at higher concentrations produces cell death. We evaluated in septal SN56 basal forebrain cholinergic neurons, the CPF effect after 24 h and 14 days exposure on dendritic spines. This study shows that CPF induces after acute and long-term exposure an alteration of dendritic spines at lower concentrations than which induces cell death. Evaluation of genes related to dendritic spine plasticity revealed that some of them are altered at lower concentrations than which produces the effects observed and below the No Observed Adverse Effect (NOAEL). The present finding suggests that the use of gene expression profile could be a more sensitive and accurate way to determine the NOAEL

Maralise Perígolo de Oliveira has completed her Master from University Grenoble Alpes and PhD from Pernambuco Federal University (Brazil) in 2014. Since 2015, her postdoctoral research in medicinal chemistry is developed in Belo Horizonte (Brazil) through collaboration from Pernambuco Federal University and Federal University of Minas Gerais.

Abasic sites are probably the most common lesions in DNA. They result from the hydrolytic cleavage of glycosidic bonds that can occur spontaneously and during the repair processes of damaged nucleic bases produced by anticancer alkylating agents and radiotherapy. If not repaired, the abasic site can be mutagenic or lethal. Thus, compounds able to specifically bind and react to abasic sites have attracted much attention for therapeutic and diagnostic purposes. Here, we report on the efficient cleavage activity of natural aminoglycosides (AG) antibiotic drugs at abasic sites. Neomycin B appeared to be the most efficient compound (EC50=0.1μM). This cleavage activity could be related to the aminoglycoside toxicity but could also find medicinal applications through potentiation of cancer radiotherapy and chemotherapy with alkylating drugs.