# N-Acetylcysteine-Amide Protects Against Acute Acrylamide Neurotoxicity in Adult Zebrafish

## TL;DR

N-Acetylcysteine-amide (AD4) protects zebrafish brains from acrylamide toxicity by restoring glutathione levels and improving behavior.

## Contribution

This study demonstrates AD4's neuroprotective efficacy in a novel zebrafish model of acute acrylamide-induced neurotoxicity.

## Key findings

- AD4 fully reversed acrylamide-induced brain glutathione depletion in zebrafish.
- AD4 rescued deficits in short-term habituation of the acoustic startle response caused by acrylamide.
- Acrylamide exposure did not alter neurotransmitter levels or gene expression related to redox or myelination.

## Abstract

Acrylamide (ACR) is a potent neurotoxicant that disrupts cellular redox homeostasis by depleting reduced glutathione (GSH) and inducing oxidative stress. Despite its well-characterized mechanism, no effective treatments for ACR-induced neurotoxicity currently exist. This study evaluates the therapeutic efficacy of N-acetylcysteine-amide (AD4), a blood–brain barrier (BBB)-permeable derivative of N-acetylcysteine, in a novel severe acute ACR neurotoxicity model in adult zebrafish. Adult zebrafish received a single intraperitoneal (i.p.) injection of ACR (800 μg/g), followed by AD4 (400 μg/g i.p.) or PBS 24 h later. ACR exposure reduced brain GSH levels by 51% reduction at 48 h, an effect fully reversed by AD4 treatment. Behavioral analyses showed that AD4 rescued ACR-induced deficits in short-term habituation of the acoustic startle response (ASR). Surprisingly, ACR exposure did not alter the neurochemical profile of key neurotransmitters or the expression of genes related to redox homeostasis, synaptic vesicle recycling, regeneration, or myelination. These results demonstrate AD4’s neuroprotective effects against acute ACR-induced brain toxicity, highlighting its therapeutic potential and validating adult zebrafish as a translational model for studying neurotoxic mechanisms and neuroprotective interventions.