Acute and long-term metabolic consequences of early developmental Bisphenol A exposure in zebrafish (Danio rerio).

Bisphenol A (BPA) is an estrogenic contaminant linked to metabolic disruption. Developmental BPA exposure is of particular concern, as organizational effects may irreversibly disrupt metabolism at later life-stages. While BPA exposures in adult fish elicit metabolic perturbations similar to effects described in rodents, the metabolic effects of developmental BPA exposure in juvenile fish remain largely unknown. Following embryonic zebrafish exposure to BPA (0.1, 1 and 4 mg/L) and EE2 (10 ng/L) from 2 to 5 dpf, we assessed the metabolic phenotype in larvae (4-6 dpf) and juveniles (43-49 dpf) which had been divided into regular-fed and overfed groups at 29 dpf. Developmental BPA exposure in larvae dose-dependently reduced food-intake and locomotion and increased energy expenditure. Juveniles (29 dpf) exhibited a transient increase in body weight after developmental BPA exposure and persistent diet-dependent locomotion changes (43-49 dpf). At the molecular level, glucose and lipid metabolism-related transcript abundance clearly separated BPA exposed fish from controls and EE2 exposed fish at the larval stage, in juveniles on a regular diet and, to a lesser extent, in overfed juveniles. In general, the metabolic endpoints affected by BPA exposure were not mimicked by EE2 treatment. We conclude that developmental BPA exposure elicits acute metabolic effects in zebrafish larvae and fewer transient and persistent effects in juveniles and that these metabolic effects are largely independent of BPA's estrogenicity.

Tetracycline antibiotics as PI3K inhibitors in the Nrf2-mediated regulation of antioxidative stress in zebrafish larvae.

Scientific concern about veterinary antibiotics (VAs) residues in the aquatic environment has increased in recent years. However, little is known about the underlying molecular mechanism of antioxidative stress caused by VAs in fish. In this study, zebrafish larvae were exposed to two representatives of VAs, chlortetracycline (CTC) and oxytetracycline (OTC), for 48 h. The oxidative stress responses and possible molecular mechanism of action were investigated. The results showed that the activities of CAT, SOD and GPx were significantly inhibited and the contents of GSH and MDA increased after CTC exposure. Moreover, SOD and CAT activity were parallel to their mRNA and protein levels. Under OTC exposure, CAT and GST activity were inhibited, while GPx activity was induced, and MDA content decreased significantly. After treatment with CTC and OTC, glucose levels and Nrf2 mRNA and protein levels in zebrafish larvae were significantly downregulated. Further molecular docking and molecular dynamics simulations revealed that CTC and OTC are capable of docking into the binding pocket of zebrafish PI3K, an important molecule in the activation of Nrf2, and can form stable interactions through hydrogen bonds. The overall results indicated that CTC and OTC significantly induced oxidative stress responses in zebrafish larvae, and both CTC and OTC act as inhibitors of PI3K to inhibit the activation of the Nrf2/ARE signaling pathway, thus reducing the antioxidant capacity of fish.