AND IP ADMINISTRATION

OCHRATOXIN A EXPOSURE INDUCES BEHAVIORAL CHANGES IN MICE AFTER ORAL AND IP ADMINISTRATION

M. Serrano1 , E. Beraza1, M. Izco2, E. González-Peñas3, A. López de Cerain1,3, A. Vettorazzi1, 3, L. Álvarez-Erviti2 1 Department of Pharmacology and Toxicology, Research Group MITOX, School of Pharmacy and Nutrition, Universidad de Navarra, Pamplona, Spain 2 Laboratory of Molecular Neurobiology, Center for Biomedical Research of La Rioja (CIBIR), Logroño, Spain 3 Department of Pharmaceutical Technology and Chemistry, Research Group MITOX, School of Pharmacy and Nutrition, Universidad de Navarra, Pamplona, Spain 4 IdiSNA, Navarra Institute for Health Research, Pamplona, Spain avettora@unav.es Ochratoxin A (OTA) is a mycotoxin that contaminates a great variety of crops. The main concern is its genotoxicity/carcinogenicity. Although poorly explored, OTA has also showed some neurotoxic effects. On the other hand, etiological factors for Parkinson’s disease (PD) are still unknown. PD is characterized by the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies which contain aggregates of alpha-synuclein (α-syn). There is increasing evidence that the transmission of the pathology between neurons plays a central role in disease progression. Braak hypothesis proposes that Lewy body pathology may arise in the periphery/enteric nervous system, possibly in the gastrointestinal (GI) tract, and transfer to the brain stem via the glossopharyngeal and vagus nerves. The aim of the present study was to evaluate if OTA induced behavioral changes in mice and to check if the observations are dependent of the route of administration. The oral route was selected to mimic human e xposure to OTA, while intraperitoneal (ip) was selected in order to avoid the GI tract. Animals were administered daily for 28 days either with vehicle or with two different OTA doses (0.21 or 0.5 mg/kg bw). Behavioral tests (wire hang, negative geotaxis and rotarod) were carried out during the administration and for 6 months after the last administration. Clinical changes, body weight and OTA levels were also monitored. OTA induced behavioral alterations with both routes of administration, although with some differences in the timeframe. No clinical signs of toxicity were observed during the studies. After oral administration, OTA was detectable after the 28 days of administration in plasma and brain but was undetectable in both tissues 6 months after the last administration. OTA analysis is still ongoing for the ip administration. Our results point to a potential neurodegenerative effect of OTA.

Funding: European Regional Development Fund (FEDER) "A way to make Europe" (6FRSABC008), “Ministerio de Economia, Industria y Competitividad, Agencia Estatal de Investigacion” of the Spanish Government (AGL2017-85732-R) (MINECO/AEI/FEDER, UE) and ¨Gobierno de Navarra” (2019-project 43). Keywords: Ochratoxin A, neurodegeneration, neurotoxicity, Parkinson´s disease, mice

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