Effects of trimethoprim on life history parameters, oxidative stress, and the expression of cytochrome P450 genes in the copepod Tigriopus japonicus

Chemosphere. 2016 Sep:159:159-165. doi: 10.1016/j.chemosphere.2016.05.085. Epub 2016 Jun 9.

Abstract

Trimethoprim (TMP) is an antibiotic that has been detected in various environments including marine habitats; however, the toxic effects of TMP are poorly understood in non-target marine organisms. In this study, the effects of TMP on mortality, development, reproduction, intracellular reactive oxygen species (ROS) levels, and transcription levels of antioxidant and xenobiotic detoxification-related enzyme genes were investigated in the copepod Tigriopus japonicus. The TMP half lethal dose at 48 h (LC50-48 h) in nauplius and TMP LC50-96 h in adult T. japonicus copepods was determined as 156 mg/L and 200 mg/L, respectively. In TMP-exposed T. japonicus, delayed developmental time and impaired reproduction were observed as harmful effects on the life history parameters. Increased ROS levels were also shown in response to TMP exposure at the highest concentration (100 mg/L TMP) and the expression of antioxidant- (e.g. GST-kappa, GST-sigma) and xenobiotic detoxification (e.g. CYPs)-related genes were upregulated in a time and/or dose-dependent manner in response to TMP. Particularly, significant upregulation of three CYP genes (Tj-CYP3024A2, Tj-CYP3024A3 and Tj-CYP3027C2) were examined, suggesting that these CYP genes are likely playing an important role in the TMP detoxification metabolism in T. japonicus. In summary, we found that TMP induced oxidative stress via the transcriptional regulation of antioxidant- and xenobiotic detoxification-related genes, leading to changes in life history parameters such as developmental delay and reproduction impairment. Three Tj-CYP genes (Tj-CYP3024A2, Tj-CYP3024A3 and Tj-CYP3027C2) could be useful as potential T. japonicus biomarkers in response to antibiotics.

Keywords: Biomarker; Copepod; Cytochrome P450; Oxidative stress; Reactive oxygen species; Tigriopus japonicus; Trimethoprim.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / toxicity*
  • Biomarkers / metabolism
  • Copepoda / drug effects*
  • Copepoda / genetics
  • Copepoda / growth & development
  • Copepoda / physiology
  • Cytochrome P-450 Enzyme System / genetics
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects
  • Life Cycle Stages / drug effects
  • Oxidation-Reduction
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / metabolism
  • Reproduction / drug effects
  • Trimethoprim / toxicity*
  • Water Pollutants, Chemical / toxicity*

Substances

  • Anti-Bacterial Agents
  • Biomarkers
  • Reactive Oxygen Species
  • Water Pollutants, Chemical
  • Cytochrome P-450 Enzyme System
  • Trimethoprim