Behavioral and Biochemical Effects of N-Acetylcysteine in Zebrafish Acutely Exposed to Ethanol

Abstract

Alcohol hangover refers to unpleasant symptoms experienced as a direct consequence of a binge drinking episode. The effects observed in this condition are related to the increase in alcohol metabolites and imbalance in oxidative status. N-acetylcysteine (NAC) is a mucolytic agent and an antidote for paracetamol overdose. Preclinical and clinical studies have shown that NAC is a multi-target drug acting through neuroprotective, antioxidant and neurotrophic mechanisms as well as a glutamate modulator. The aim of this study was to investigate the effects of NAC in zebrafish acutely exposed to ethanol (EtOH). Animals pretreated or not with NAC (1 mg/L, 10 min) were exposed for 60 min to standard tank water (EtOH-) or to 1% EtOH (EtOH+) to evaluate anxiety-like behavior and locomotion in the novel tank test and oxidative damage in the brain. Zebrafish (Danio rerio) exposed to EtOH displayed a decrease in the distance traveled, crossings, entries and time spent in the top area in the novel tank test. Exposure to EtOH also caused oxidative damage, shown by increased lipid peroxidation, decreased non-protein thiols and increased production of reactive oxygen species (DCF assay). NAC prevented both the behavioral alterations and the oxidative stress observed in EtOH+ animals. Given the effects of NAC in preventing the acute behavioral and biochemical effects of EtOH, additional studies are warranted to further investigate the basis of its anecdotal use to prevent hangover.

Peer Review #3 of "Repeated ethanol exposure increases anxiety-like behaviour in zebrafish during withdrawal (v0.2)"

“…Another possible explanation is the difference in strain of zebrafish used; AB strain (Mathur and Guo, 2011) compared to wild-type in our study and others (ex. Rosemberg, 2012;Mocelin et al, 2018;Müller et al, 2017). After 8 days of exposure to 1% ethanol for 20 minutes per day, social…”

“…Manuscript to be reviewed longer durations of ethanol exposure (1 hour) the anxiolytic effect on behaviour seems to change to an anxiogenic state (Rosemburg et al, 2012;Mocelin et al, 2018). Studies examining chronic ethanol exposure in zebrafish have reported inconsistent results, possibly due to the many different exposures times, duration of exposure, duration of withdrawal, and concentration of ethanol used (da Silva Chaves et al, 2018).…”

N-acetylcysteine protects against motor, optomotor and morphological deficits induced by 6-OHDA in zebrafish larvae

“…The medium was not changed until 3 dpf. NAC concentration was determined in a pilot study as well as in our previous studies ( Mocelin et al, 2015 , 2017 ).…”

Anxiolytic and anti-stress effects of acute administration of acetyl-L-carnitine in zebrafish

“…The upper zone of the tank corresponds in rats and mice protocols to the periphery region of the open-field test. Alterations in time spent and number of crossings to this zone are frequently used as a parameter of anxiety in zebrafish ( Mocelin et al, 2015 ; Giacomini et al, 2016 ; Marcon et al, 2016 ; Mocelin et al, 2017 ; Marcon et al, 2018 ).…”

“…Samples were collected and prepared as previously reported by Mocelin et al (2018) . Specifically, after the ACS fish were anesthetized by immersion in cold water and euthanized by decapitation.…”