Adverse effects of two pharmaceuticals acetaminophen and oxytetracycline on life cycle parameters, oxidative stress, and defensome system in the marine rotifer Brachionus rotundiformis

Aquat Toxicol. 2018 Nov:204:70-79. doi: 10.1016/j.aquatox.2018.08.018. Epub 2018 Aug 27.

Abstract

To investigate the adverse effect of two widely used pharmaceuticals, paracetamol (acetaminophen [APAP]) and oxytetracycline (OTC) on the marine rotifer Brachionus rotundiformis (B. rotundiformis), the animals were exposed to various environmentally-relevant concentrations. Up to date, acetaminophen and oxytetracycline have been considered as toxic, if used above threshold concentration, i.e. overdosed. However, this study demonstrated these two pharmaceuticals even at low concentration (i.e., μg/L scale) elicited oxidative stress through the generation of reactive oxygen species (ROS) along with the increased glutathione S-transferase activity, despite no-observed effect in in-vivo population growth. To validate the adverse effects of the two pharmaceuticals at relatively low concentrations, mRNA expression analysis was performed of the entire set of genes encoding 26 cytochrome P450s (CYPs) of phase I and 19 glutathione S-transferases (GSTs) of phase II of the rotifer B. rotundiformis. The mRNA expression analysis suggested specific genes CYP3045A2 and GSTσ1, GSTσ4, and GSTω1 take part in detoxification of APAP and OTC, resulting in no significant changes in the population growth and undetermined no observed effect concentration (NOEC) in the marine rotifer B. rotundiformis.

Keywords: Acetaminophen; Brachionus rotundiformis; Defensome; Oxidative stress; Oxytetracycline; Rotifer.

MeSH terms

  • Acetaminophen / adverse effects*
  • Acetaminophen / chemistry
  • Animals
  • Antioxidants / metabolism
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Gene Expression Regulation, Enzymologic / drug effects
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism
  • Life Cycle Stages / drug effects*
  • Oxidative Stress / drug effects*
  • Oxytetracycline / adverse effects*
  • Oxytetracycline / chemistry
  • Reactive Oxygen Species / metabolism
  • Rotifera / drug effects
  • Rotifera / enzymology
  • Rotifera / growth & development*
  • Rotifera / immunology*
  • Toxicity Tests, Acute
  • Water Pollutants, Chemical / toxicity

Substances

  • Antioxidants
  • Reactive Oxygen Species
  • Water Pollutants, Chemical
  • Acetaminophen
  • Cytochrome P-450 Enzyme System
  • Glutathione Transferase
  • Oxytetracycline