Impact of the Antidiabetic Drug Metformin and Its Transformation Product Guanylurea on the Health of the Big Ramshorn Snail (Planorbarius corneus)

Abstract

Pharmaceuticals can enter surface waters via sewage treatment plants. In the environment, the substances and their transformation products, formed by the degradation of the parent compounds, can affect aquatic wildlife, including freshwater invertebrates. However, research on pharmaceutical-induced effects in wild freshwater organisms other than fish is still scarce. In our study, we 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) by analysing its biochemical and cellular stress responses and apical parameters. The snails were exposed to different concentrations of the drug (0, 0.01, 0.1, 1, and 10 mg/L) and its transformation product (0, 0.1, 10, and 100 mg/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 mg/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 observed 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 a major concern that metformin and guanylurea could pose a risk to the big ramshorn snail in the environment.

Effects of the Antidepressants Citalopram and Venlafaxine on the Big Ramshorn Snail (Planorbarius corneus)

“…Yet, no studies exist in literature regarding histopathology in invertebrates and antidepressants. However, effects similar to those found in the present study, in response to citalopram, have been detected in Marisa cornuarietis exposed to platinum, copper, and lithium, as well as in P. corneus exposed to the metformin transformation product guanylurea [42][43][44]. Furthermore, irregular compartmentation of digestive cells was been reported for Xeropicta derbentina, Cernuella virgata, and Theba pisana after heat stress, as well as in Lymnea stagnalis exposed to the endosulfan-based pesticide Thiodan ® [45,101].…”

“…Therefore, the chemicals metabolized by the hepatopancreas could have an impact on its integrity. Histological effects in the hepatopancreas of snails resulting from exposure to organic chemicals or metals have been described by several authors [42][43][44][45][46][47][48]. Commonly, histological effects in the hepatopancreas are accepted as indicators for the general health status of the exposed organisms.…”

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

“…The biochemical analyses of lipid peroxides and stress proteins did not reveal any influences of guanylurea on these stress parameters in larval and juvenile brown trout. Likewise, in big ramshorn snails ( Planorbarius corneus ) exposed to 0.1–100 mg/L guanylurea for 21 days, lipid peroxides and stress proteins were not changed by guanylurea (Jacob et al, 2019). Thus, one explanation could be that guanylurea does not induce proteotoxic or oxidative stress at all.…”

Salient to Whom? The Positioning of German Political Parties on Agricultural Pollutants in Water Bodies

“…Micropollutants occur at very small concentrations, with a maximum of around one microgram per liter, which differentiates them from other pollutants [62]. They can be traced back to a diverse set of entry points from many different sectors, including agriculture, energy (mainly heavy metals from coal energy [63][64][65][66]), or the pharmaceutical industry (through communal wastewater [67][68][69][70][71][72][73]). When designing policies to ensure water protection and improve water quality, these sectors must be addressed as well in order to find effective and sustainable solutions.…”