BRAIN MITOCHONDRIAL DYSFUNCTION AND CHANGES IN NITRIC OXIDE METABOLISM INDUCED BY LEVOCABASTINE ADMINISTRATION

A.G. KARADAYIAN; S. LORES-ARNAIZ; G. RODRÍGUEZ DE LORES ARNAIZ; A. GUTNISKY

Buenos Aires

Congreso; Primer Congreso de Ciencias Biomédicas; 2017

SAIC-SAFE-SAB-SAFIS

Mitochondrial function is modified by nitric oxide (NO). Levocabastine, an antagonist for low affinity neurotensin receptor (NTS2), alters NO metabolism in synaptosomal membrane fractions devoided of mitochondria. The purpose of the present study was to evaluate the potential involvement of NTS2 receptor activity in mitochondrial function and NO metabolism. Wistar rats were injected with levocabastine (50 μg/kg, i.p.) or vehicle (saline solution) and decapitated 30 min or 18 hours later. Oxygen consumption and total NO levels were evaluated in crude mitochondrial fractions. Enzymatic activities of mitochondrial respiratory complexes, monoamine oxidase (MAO) and nitric oxide synthase (NOS), as well as neuronal NOS (nNOS) protein expression were evaluated in purified mitochondria. Crude mitochondrial fractions were capable of generating NO, as detected by flow cytometry. Assays of oxygen consumption showed no response to oligomycin or FCCP additions in levocabastine-treated rats. Mitochondrial respiration assays in the presence of malate-glutamate or succinate showed that levocabastine decreased mitochondrial respiratory controls assayed ex vivo and in vitro. The activity of mitochondrial complexes I-III, II-III and IV decreased 60%, 63% and 42%, at 30 min after levocabastine administration and 83%, 82% and 74%, at 18 hours after the treatment respectively (p