Embryonic exposure to butylparaben and propylparaben induced developmental toxicity and triggered anxiety‐like neurobehavioral response associated with oxidative stress and apoptosis in the head of zebrafish larvae

Abstract

Parabens are synthetic antimicrobial compounds used as a preservative for extending the shelf life of food, pharmaceutical and cosmetic products. The alkyl chain length of the paraben esters positively correlates with their antimicrobial property. Hence, long-chain paraben esters, namely butylparaben and propylparaben, are used in combination as they have better solubility and antimicrobial efficacy. Extensive use of parabens has now resulted in the ubiquitous presence of these compounds in various human and environmental matrices. During early life, exposure to environmental contaminants is known to cause oxidative-stress mediated apoptosis in developing organs. The brain being one of the high oxygen-consuming, metabolically active and lipid-rich organ, it is primarily susceptible to reactive oxygen species (ROS) and lipid peroxidation (LP) induced neuronal cell death. The primary cause for the impairment in cognitive and emotional neurobehvioural outcomes in neurodegenerative disease was found to be associated with neuronal apoptosis. The present study aimed to study butylparaben and propylparaben's effect on zebrafish during early embryonic stages. Besides this, the association between alteration in anxiety-like neurobehavioral response with oxidative stress and antioxidant status in head region was also studied. The study results showed variation in the toxic signature left by butylparaben and propylparaben on developmental parameters such as hatching rate, survival and non-lethal malformations in a time-dependent manner. Data from the light-dark preference test showed embryonic exposure to butylparaben and propylparaben to trigger anxiety-like behavior in zebrafish larvae. In addition, a significant increase in intracellular ROS and LP levels correlated with suppressed antioxidant enzymes: superoxide dismutases (SOD), catalases (CAT), Glutathione peroxidase (GPx), glutathione S-transferase (GST), and Glutathione (GSH) activity in the head region of the zebrafish larvae. Acetylcholinesterase (AChE) activity was also suppressed in the exposed groups, along with increased nitric oxide production. The overall observations show increased oxidative stress indices correlating with upregulated expression of apoptotic cells in a dose-dependent manner. Collectively, our findings reveal butylparaben and propylparaben as an anxiogenic neuroactive compound capable of inducing anxiety-like behavior through a mechanism involving oxidative-stress-induced apoptosis in the head of zebrafish larvae, which suggests a potential hazard to the early life of zebrafish and this can be extrapolated to human health as well.