Integrated molecular and metabolomic assessment of copper hydroxide nanopesticide toxicity in zebrafish


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Aksakal F. I., Gür C., Şişman T., Özli S., Şenol O., Aksakal Ö.

Fish Physiology and Biochemistry, cilt.52, sa.3, 2026 (SCI-Expanded, Scopus) identifier identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 52 Sayı: 3
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1007/s10695-026-01701-4
  • Dergi Adı: Fish Physiology and Biochemistry
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Zoological Record, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Earth, Atmospheric, & Aquatic Science Collection (ProQuest), Health Research Premium Collection (ProQuest), Pharma Collection (ProQuest)
  • Anahtar Kelimeler: Apoptosis, Copper homeostasis, Cu(OH)(2) nanopesticide, Endoplasmic reticulum stress, Metabolomics
  • Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
  • Atatürk Üniversitesi Adresli: Evet

Özet

Copper hydroxide (Cu(OH)2) nanopesticides [Cu(OH)2 NP] are increasingly applied in agriculture, raising concerns about their potential risks to non-target aquatic organisms. In this study, we investigated the toxic effects of Cu(OH)2 NP exposure in zebrafish (Danio rerio) larvae and adults using an integrated gene expression and metabolomic approach. Zebrafish embryos were exposed to sublethal concentrations of Cu(OH)2 NP until 96 h post-fertilization, while adults were subjected to a 14-day sub-chronic exposure. Cu(OH)2 NP significantly altered the expression of genes involved in copper homeostasis and redox regulation (cox16, atp7a, ccs, and gclm), accompanied by activation of endoplasmic reticulum stress (atf6, perk, and ire1) and apoptosis-related pathways (casp3, casp9, bax, and bcl2). These responses were dose-dependent and more pronounced in zebrafish larvae and adult liver tissue. Metabolomic analysis revealed substantial metabolic reprogramming, particularly affecting energy metabolism, amino acid pathways, and glutathione metabolism. In adult zebrafish, significant changes in hepatosomatic index (HSI) indicated disrupted energy balance and hepatic stress. Integrated analysis suggests that Cu(OH)2 NP toxicity is associated with disruption of copper homeostasis and activation of cellular stress-response pathways. Overall, these findings improve our understanding of the molecular and metabolic responses of zebrafish to Cu(OH)2 NP exposure and highlight potential ecological risks of nano-enabled agrochemicals.