n-Butyl acrylate-induced antioxidant system alteration through two generations in Oryzias latipes.

n-Butyl acrylate (nBA) is one of acrylate esters which has been applied to diverse industrial fields. For unveiling of xeno-estrogenic effects and oxidative stress induction by nBA under two-generational exposure regimen (17 weeks), the biomarkers relevant to an estrogenic effect and oxidative stress were analyzed. Acute toxicity value of nBA in Oryzias latipes was 7.2 mg/L (96 h-LC50). Over exposure time, the significant transcriptional change of cytochrome P450 19A (CYP19A) and vitellogenin 1/2 (VTG1/2) was not observed (one-way ANOVA, P < 0.05), meaning no estrogenic effect of nBA. Significant reduction of glutathione (GSH) content was observed in F0 male and female fish, while in F1 male, the content was increased (P < 0.05). Catalase (CAT) activity of male fish showed the significant decrease in both F0 and F1 fish, showing multi-generational suppressing effect of nBA on CAT activity. But in case of reactive oxygen species (ROS), expression level and glutathione S-transferase (GST) activity were not modulated in response to nBA. These findings suggest that nBA could affect an antioxidant system alteration through GSH depletion and inhibition of CAT activity which could be transferred to the next generation, whereas xeno-estrogenic effect would be questionable.

Metformin-induced endocrine disruption and oxidative stress of Oryzias latipes on two-generational condition.

Metformin has been treated for diabetes (type 2). Nowadays, this compound is frequently found in ambient water, influent/effluent of a wastewater treatment plant. To evaluate the metformin aquatic toxicity under a multi-generational exposure regimen, we exposed Oryzias latipes to metformin for two generations (133 d) and investigated its adverse effects. In the F0 generation, metformin significantly elevated gene expression for cytochrome P450 19a (CYP19a) and estrogen receptor α (ERα) in male fish; in female fish, the treatment decreased gene expression of vitellogenin (VTG2) and ERß1, suggesting endocrine disruption (one-way ANOVA, p < 0.05). Intersex occurrence of F0 female fish were found in a concentration-dependent manner, whereas no significant changes in fecundity and hatching rate were observed (p < 0.05). Metformin increased the reactive oxygen species (ROS) content, and decreased the glutathione (GSH) content in F0 male fish compared with those of the control (one-way ANOVA, p > 0.05). In F0 female fish, metformin increased catalase activity compared with that of the control (p > 0.05). The results demonstrated that metformin leads to oxidative stress and two-generation endocrine disruption in O. latipes. These results may be useful for better understanding metformin toxicity mechanism.