Dietary exposure to the food preservative tert-Butylhydroquinone (tBHQ) impairs zebrafish (Danio rerio) survival, growth, organ development, and gene expression in Nrf2a-dependent and independent ways

Abstract

Tert-Butylhydroquinone (tBHQ), a preservative used to prevent oxidative deterioration of oil, fat, and meat products, has been linked to both chemoprotective and adverse effects. This study investigates the impact of dietary tBHQ consumption on survival, growth parameters, organ development, and gene expression in zebrafish (Danio rerio). As tBHQ activates the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2a), a zebrafish line with a mutation in the DNA-binding domain of Nrf2a was used to identify Nrf2a-dependent vs independent effects. Homozygous Nrf2a wildtype (wt) and mutant (m) larvae were fed a diet containing 5% tBHQ or a control diet. Survival and growth parameters were assessed at 15 days and at 5 months, and samples were collected for RNA sequencing at 5 months. Dietary exposure to tBHQ throughout the larval and juvenile periods negatively impacted growth and survival. RNA-seq analysis found differentially expressed genes related to growth and development and upregulation of several immune system-related pathways. The findings herein demonstrate that dietary tBHQ exposure may impair growth and survival in both Nrf2a dependent and independent manners.

Keywords: Antioxidant defenses; Embryonic development; Nrf2; Pancreatic islet; Redox; Tert-Butylhydroquinone (tBHQ).