Evaluation and comparison of the mitochondrial and developmental toxicity of three strobilurins in zebrafish embryo/larvae

Strobilurin fungicides have been frequently detected in aquatic environments and can induce mitochondrial toxicity to non-target aquatic organisms. However, the derived toxicity and subsequent mechanisms related to their adverse effects are not fully elucidated. In the present study, we compared the mitochondrial and developmental toxicity of azoxystrobin, pyraclostrobin, and trifloxystrobin using zebrafish embryo/larvae. The results showed that all three strobilurins inhibited mitochondrial and non-mitochondrial respiration (the potency is pyraclostrobin approximate to trifloxystrobin > azoxystrobin). Behavioral changes indicated that sublethal doses of pyraclostrobin and azoxystrobin caused hyperactivity of zebrafish larvae in dark cycles, whereas trifloxystrobin resulted in hypoactivity of zebrafish larvae. In addition, pyraclostrobin exposure impaired the inflation of swim bladder, and caused down-regulation of annexin A5 (anxa5) mRNA levels, and up-regulated transcript levels of pre-B-cell leukemia homeobox 1a (pbx1a); conversely, azoxystrobin and trifloxystrobin did not cause detectable effects with swim bladder inflation. Molecular docking results indicated that azoxystrobin had higher interacting potency with iodotyrosine deiodinase (IYD), prolactin receptor (PRLR), antagonistic conformation of thyroid hormone receptor beta (TR beta) and glucocorticoid receptor (GR) compared to pyraclostrobin and trifloxystrobin; pyraclostrobin and azoxystrobin were more likely to interact with the antagonistic conformation of TR beta and GR, respectively. These results may partially explain the different effects observed in behavior and swim bladder inflation, and also point to potential endocrine disruption induced by these strobilurins. Taken together, our study revealed that all three strobilurins alter mitochondrial bioenergetics and cause developmental toxicity. However, the toxic phenotypes and underlying mechanisms of each chemical may differ, and this requires further investigation. Pyraclostrobin showed higher mitochondrial toxicity at lethal doses and higher developmental toxicity at sublethal doses compared to the two other strobilurins tested. These results provide novel information for toxicological study as well as risk assessment of strobilurin fungicides. (C) 2020 Elsevier Ltd. All rights reserved.

Automated summary

Strobilurin fungicides have been found in aquatic environments and can induce mitochondrial toxicity in non-target aquatic organisms. The three strobilurins tested in this study all inhibit mitochondrial and non-mitochondrial respiration, with varying effects on behavior and swim bladder inflation in zebrafish larvae. Further investigation is needed to understand the toxic phenotypes and underlying mechanisms of each chemical. Pyraclostrobin showed higher mitochondrial toxicity at lethal doses and higher developmental toxicity at sublethal doses compared to the other two strobilurins.