Transcriptome-Guided Characterization of the Environmental Toxicity of Metformin: Disruption of Energy Homeostasis and Inhibition of Embryonic Development of Zebrafish at Environmentally Relevant Concentrations
Ziyu Zhang, Haochun Shi, Kun Zhang, Ruiqi An, Congcong Wang, Peng Wang, Shen-An Chan, Yue Song, Jiayin Dai, Yanbin Zhao
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引用次数: 0
Abstract
Metformin has been widely detected in aquatic ecosystems, yet the knowledge of its impact on aquatic organisms, particularly at environmentally relevant concentrations, remains limited. In the present study, we characterized the developmental toxicity of metformin in zebrafish, utilizing a transcriptome-guided toxicological assessment framework. Transcriptomic analysis conducted at metformin concentrations within the μg/L range revealed significant disruptions in biological processes associated with nucleotide, hydrocarbon, and amino acid metabolism, suggesting a significant disturbance in energy homeostasis. This observation was corroborated by energy-targeted metabolomic analysis, wherein a considerable number of metabolites involved in purine metabolism, pyrimidine metabolism, and the citrate cycle displayed significant alterations. Notably, most intermediates in the citrate cycle such as acetyl-CoA exhibited remarkable decreases. Additionally, our study identified significant impediments in zebrafish embryonic development, including decreased yolk extension progress, spontaneous contraction and body length, and increased yolk sac area and yolk/while body lipid content ratio, at metformin concentrations as low as 0.12 μg/L. Furthermore, the disruption of energy homeostasis by metformin was observed to persist into adulthood even after a prolonged recovery period. The present findings highlighted the disruptive effects of metformin on energy homeostasis and embryonic development in teleost at environmentally relevant concentrations, thereby prompting a reevaluation of its environmental risk to nontarget aquatic organisms.
期刊介绍:
Environmental Science & Technology (ES&T) is a co-sponsored academic and technical magazine by the Hubei Provincial Environmental Protection Bureau and the Hubei Provincial Academy of Environmental Sciences.
Environmental Science & Technology (ES&T) holds the status of Chinese core journals, scientific papers source journals of China, Chinese Science Citation Database source journals, and Chinese Academic Journal Comprehensive Evaluation Database source journals. This publication focuses on the academic field of environmental protection, featuring articles related to environmental protection and technical advancements.