Effects of guanylurea, the transformation product of the antidiabetic drug metformin, on the health of brown trout (Salmo trutta f. fario)

PeerJ. 2019 Jul 11:7:e7289. doi: 10.7717/peerj.7289. eCollection 2019.

Abstract

Background: Guanylurea is the main transformation product of the antidiabetic drug metformin, which is one of the most prescribed pharmaceuticals worldwide. Due to the high rate of microbial degradation of metformin in sewage treatment plants, guanylurea occurs in higher concentrations in surface waters than its parent compound and could therefore affect aquatic wildlife. In this context, data for fish are scarce up to now which made us investigate the health of brown trout (Salmo trutta f. fario) in response to guanylurea.

Methods: In two experiments, eggs plus developing larvae and juvenile brown trout were exposed to three different concentrations of guanylurea (10, 100 and 1,000 µg/L) and, as a negative control, filtered tap water without this compound. Low internal concentrations were determined. The investigated parameters were mortality, length, weight, condition factor, tissue integrity of the liver and kidney, levels of stress proteins and lipid peroxides, as well as behavioural and developmental endpoints. It was found that guanylurea did not significantly change any of these parameters in the tested concentration range.

Results: In conclusion, these results do not give rise to concern that guanylurea could negatively affect the health or the development of brown trout under field conditions. Nevertheless, more studies focusing on further parameters and other species are highly needed for a more profound environmental risk assessment of guanylurea.

Keywords: Brown trout; Histopathology; Lipid peroxides; Pharmaceutical; Stress proteins; Swimming behaviour; Transformation product.

Grants and funding

This study is funded by the Ministry for Science, Research and Arts of Baden- Württemberg (Grant No. 33-5733-25-11t32/2). Minor parts of the project were financed by the German Excellence Initiative commissioned by the German Research Foundation (DFG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.