Developmental anomalies and oxidative stress responses in zebrafish (danio rerio) following embryonic exposure to human pharmaceuticals

Adeolu O. Aderemi*, Colin Hunter, Ole Pahl, Joanne Roberts, Xinhua Shu

*Corresponding author for this work

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The discharge of human pharmaceuticals via wastewater treatment plants represents a major threat to non-target aquatic organisms since they are continually exposed throughout their lifespan. The individual effects of the anaesthetic, lidocaine; the cytostatics, ifosfamide and cyclophosphamide; and the antimicrobials, sulfamethoxazole, amoxicillin and erythromycin on 24 hpf (hours post fertilization) zebrafish (Danio rerio) following a 96-h exposure was investigated by evaluating embryonic development, catalase (CAT) enzyme activity, and the gene expressions of CAT, cytosolic superoxide dismutase (SOD1), and mitochondrial superoxide dismutase (SOD2). Lidocaine, cyclophosphamide and sulfamethoxazole induced neurotoxicity (scoliosis, tail malformation) and cardiotoxicity (pericardial edema, bradycardia) in the zebrafish which correlate with their adverse effects in mammals. These observations were linked to oxidative stress as indicated by the significant alteration of CAT activity and amounts of transcripts of SOD1, SOD2, and CAT. The CAT activity and gene expressions of the antioxidants were significantly upregulated at sublethal and levels of ifosfamide, lidocaine, cyclophosphamide, and erythromycin non-toxic to embryonic development in this study which suggest that these antioxidants may play a role in the prevention of teratogenicity in the larvae. The multi-level effect approach adopted in this study provides a better understanding of the mechanisms of toxicity employed by lidocaine, cyclophosphamide and sulfamethoxazole towards zebrafish. This study shows the importance of evaluating stress biomarkers and emphasizes the need for chronic studies in assessing pharmaceutical effects on aquatic organisms.

Original languageEnglish
Pages (from-to)109-125
Number of pages17
JournalInternational Journal of Toxicology and Environmental Health
Issue number1
Publication statusPublished - 31 Jul 2020


  • zebrafish
  • pharmaceuticals
  • developmental toxicity
  • antioxidants
  • biomarkers
  • gene expression


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