Abstract
Pharmaceuticals can enter surface waters via sewage treatment plants. In the environment, the substances and their transformation products, formed by degradation of the parent compounds, may affect aquatic wildlife including freshwater invertebrates. However, research on pharmaceutical-induced effects in feral freshwater organisms other than fish is still scarce to date. In our study, we therefore investigated the impact of the highly consumed antidiabetic drug metformin and its main transformation product guanylurea on the health of a freshwater gastropod – the big ramshorn snail (Planorbarius corneus) with respect to biochemical and cellular stress responses and apical parameters. The snails were exposed to different concentrations of the drug (0, 10, 100, 1000, 10 000, 100 000 µg/L) and its transformation product (0, 100, 10 000, 100 000 µg/L). The examined parameters were mortality, weight, tissue integrity of the hepatopancreas and the levels of stress proteins and lipid peroxides. Mortality and the levels of stress proteins and lipid peroxides were not influenced by the two substances. In response to the highest concentrations of both chemicals, the weight of the snails was slightly but not significantly reduced. The histopathological investigation of the hepatopancreas revealed a significant effect of guanylurea at a concentration of 100 000 µg/L with an increased number of symptoms of cellular responses in the tissue (e.g. dilated lumen, disturbed compartmentation of the digestive cells, nucleus deformation, hyperplasia and hypertrophy of crypt cells). For the parent compound, a similar trend was also revealed for the highest concentration. Overall, the observed effects did not occur at environmentally relevant concentrations, but at concentrations which were 10 000 times higher than these. Thus, the results did not give rise to major concern that metformin and guanylurea may pose a risk to the big ramshorn snail in the environment.
Highlights
The antidiabetic drug metformin, which is used to treat type 2 diabetes, is one of most prescribed pharmaceuticals worldwide (Gong et al, 2012; Scheurer et al, 2012)
The aim of our study was to investigate whether the two substances can influence the health of the big ramshorn snail (Planorbarius corneus) by: (1) investigating mortality and body weight, (2) analysing stress proteins in the hepatopancreas and the lipid peroxide level in the foot, and (3) examining the histopathological effects in the hepatopancreas
There was a trend of reduced body weight in the exposure groups with 0.1–10 mg/L metformin and 10 and 100 mg/L guanylurea
Summary
The antidiabetic drug metformin, which is used to treat type 2 diabetes, is one of most prescribed pharmaceuticals worldwide (Gong et al, 2012; Scheurer et al, 2012). The hepatic metabolism of metformin is negligible (Scheen, 1996) and ∼52% of the drug is excreted in the urine after 48 h in humans (Pentikäinen et al, 1979). It can enter sewage treatment plants at concentrations of 101– 129 μg/L (Scheurer et al, 2009). Caldwell et al (2019) showed that the geometric average of the no observed effect concentrations (NOEC) of five OECD 211 chronic reproduction tests with Daphnia magna was 45.2 mg/L for metformin. To the best of our knowledge, no study so far has focussed on the effects of metformin and guanylurea on freshwater gastropods. The aim of our study was to investigate whether the two substances can influence the health of the big ramshorn snail (Planorbarius corneus) by: (1) investigating mortality and body weight, (2) analysing stress proteins in the hepatopancreas and the lipid peroxide level in the foot, and (3) examining the histopathological effects in the hepatopancreas
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