ALDH2 Activity Recovery by nicotinamide adenine dinucleotide (NAD+) Treatment In Neuroblastoma SH-SY5Y Cells Exposed To Lead And Ethanol

DEZA PONZIO, ROMINA; CEJAS, ROMINA B; ALBRECHT, PAULA A.; FERNANDEZ HUBEID, LUCIA E; CANCELA, LILIANA M.; IRAZOQUI, FERNANDO J; VIRGOLINI, MIRIAM B.

Maceio

Congreso; 51st Annual Congress. Sociedad Brasilera de Farmacología y Terapéutica; 2019

Sociedad Brasilera de Farmacologia y Terapia

INTRODUCTION: Several evidences demonstrate that the neurotoxicant lead (Pb) induces neurobehavioral alterations, including an altered response to drugs. We have previously reported that perinatally-Pb-exposed rats showed elevated ethanol (EtOH) intake. It is known that EtOH metabolism determines its motivational properties. In fact, centrally-formed acetaldehyde (ACD) promotes EtOH consumption, while peripheral ACD accumulation induces aversive effects. In both cases, aldehyde dehydrogenase (ALDH) is responsible for ACD oxidation to acetic acid. In the Pb-exposed rats, the elevated EtOH intake seems to be mediated by brain ACD accumulation, probably due to a reduced mitochondrial ALDH (ALDH2) activity and expression evidenced in these animals. METHODS: In search of a mechanistic approach, in vitro experiments were performed in SH-SY5Y cells, aimed to evaluate ALDH2 activity in a brain like-environment. Neuroblastoma cells were exposed to Pb (5-200µM), EtOH (100-200 mM) or Pb + EtOH (10µM/200mM) for 24 h. RESULTS AND CONCLUSION: The results resembled the in vivo data showing that Pb alone (5µM and 10µM) or in combination with EtOH inhibited ALDH2 activity in SH-SY5Y cells. Concomitant supplementation with 1Mm of nicotinamide adenine dinucleotide (NAD+) seems to recover the enzyme activity. Current studies are focalized in the assessment of ALDH2 expression and mitochondrial functionality in this model to explore the mechanisms that modulate ALDH2 function and ACD toxicity in the presence of Pb and EtOH.