Journal of Drug Metabolism & Toxicology
Open Access
ISSN: 2157-7609
+44-77-2385-9429
ISSN: 2157-7609
+44-77-2385-9429
Javier del Pino1, Paula Moyano1, MarÃ?Âa JesÃ?ºs DÃ?Âaz1, MarÃ?Âa JosÃ?© AnadÃ?³n1, Margarita Lobo1, Jimena GarcÃ?Âa2, Miguel AndrÃ?©s Capo1 and MarÃ?Âa Teresa Frejo1
1Complutense University, Spain 2Alfonso X University, Spain
Posters-Accepted Abstracts: J Drug Metab Toxicol
Amitraz is a formamidine pesticide widely used as an insecticide and acaricide. Many amitraz poisoning cases in humans have been reported worldwide and still being described up today, which is a cause of concern for health authorities. The amitraz has been reported to be a neurotoxic compound inducing convulsion among other effects. The alpha-2 adrenergic agonist and/or local anesthetic-like properties of these compounds have been reported as likely responsible for the seizure enhancing effects. Moreover, other mechanism could be implicated. In this regard Amitraz it is an inhibitor of H1 receptor and the inhibition of histamine H1 receptor has also been implicated in seizure induction. Amitraz seizure induction could be mediated by some of the mechanism commented through a dysfunctions on GABAergic systems. To confirm if amitraz disrupt GABAergic transmission by local anesthetic-like action, inhibition of H1 receptor and activation of alpha-2 receptor, we evaluated, in primary hippocampal neurons, the effect of amitraz (0.01�¼M 100 �¼M) with or without idazoxan (1 �¼M) and/or n-methylhistaprodifen (30�¼M) and lidocaine (20mM) co-treatment on 4-aminobutyrate aminotransferase (GABAT), Glutamate Decarboxylase 65 (GAD65), succinate-semialdehyde dehydrogenase (SSADH) gene expression and GABA levels after 24 h treatment. We observed that amitraz alter GABAergic transmission disrupting the expression of GAD 65 and thus GABA levels. These effects were mediated partially by H1 and alpha-2 receptors suggesting that other mechanism could be implicated. These data help to explain the way amitraz induce seizures and a way to protect against this effect in the cause of poisoning.
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 2012 he got a position as Assistant Professor of Toxicology at the Complutense University of Madrid.
Email: jdelpino@pdi.ucm.es