ASSESSMENT OF THE TOXIC EFFECTS OF ROTENONE IN CAENORHABDITIS ELEGANS: A FUNCTIONAL RELEVANCE FOR THE METABOLISM OF TOXIC ALDEHYDES?

FERNANDEZ HUBEID, LE; ALBRECHT P.A.; DEZA-PONZIO R; VIRGOLINI MB

Rosario

Congreso; Second Latin American C. elegans Meeting. Rosario, Argentina, Febrero de 2020.; 2020

Instituto de Biologia Celular y Molecular de Rosario

ASSESSMENT OF THE TOXIC EFFECTS OF ROTENONE IN CAENORHABDITIS ELEGANS: A FUNCTIONAL RELEVANCE FOR THE METABOLISM OF TOXIC ALDEHYDES?Lucía Fernandez-Hubeid, Paula A. Albrecht, Romina Deza-Ponzio, Miriam B. VirgoliniIFEC-CONICET. Depto. de Farmacología. Facultad de Ciencias Químicas. Universidad Nacional de Córdoba. Haya de la Torre esq. Medina Allende, Córdoba, CP 5000, Argentina.luciahubeid@gmail.comThe NAD+-dependent ALDH superfamily is associated with physiological and pathological processes. These enzymes play a key role in toxic aldehydes disposition, not only of oxidative stress and ethanol metabolism bioproducts but also those resultant of biogenic amines degradation, including DOPAL (3, 4-dihidroxyphenylacetaldehyde), dopamine (DA) first metabolite. In this respect, a new body of research suggests that ALDH2 dysfunction may contribute to a variety of human conditions, including neurodegenerative diseases. In this line rotenone, a NAD+ reoxidation disruptor by complex I inhibition has been associated with the environmental etiology of Parkinson?s disease. Thus, in the present study, we sought to describe the potential toxicity of the pesticide rotenone in the model organism Caenorhabditis elegans. Wild type N2 worms were maintained in agar plates in the presence of OP50 E. coli and exposed to rotenone at 0, 2, 4, 6, 8 and 10 µM concentrations during 24 h to evidence the survival rate and morphological changes. The results demonstrated that the doses selected failed to evidence lethality, although a reduction in the worm?s size was observed. In the same line, an alteration in the basal slowing response, a DA-dependent behavior was observed. Overall, we propose rotenone as a useful tool to modulate ALDH functionality and thereby toxic aldehydes accumulation which may have important implications for the catecholaldehydic hypothesis of the neurodegenerative diseases.Funded by: MinCyT, CONICET and SeCyT-UNC, Argentina.BibliographyGoldstein DS, Sullivan P, Cooney A, Jinsmaa Y, Kopin IJ, Sharabi Y. Rotenone decreases intracellular aldehyde dehydrogenase activity: implications for the pathogenesis of Parkinson´s disease. Journal of Neurochemistry. 2015 Apr; 133 (1): 14-25.Casida JE, Ford B, Jinsmaa Y, Sullivan P, Cooney A, Goldstein DS. Benomyl, Aldehyde Dehydrogenase, DOPAL, and the Catecholaldehyde Hypothesis for the Pathogenesis of Parkinson?s disease. Chemical research in toxicology 2014 Aug; 27(8): 1359-61.Maulik M, Mitra S, Bult-Ito A, Taylor BE, Vayndorf EM. Behavioral Phenotyping and Pathological Indicators of Parkinson?s disease in C. elegans Models. Frontiers in genetics. 2017 Jun; 13: 8-77.