An ‘omics approach to investigate the growth effects of environmentally relevant concentrations of guanylurea exposure on Japanese medaka (Oryzias latipes)

Metformin Contamination in Global Waters: Biotic and Abiotic Transformation, Byproduct Generation and Toxicity, and Evaluation as a Pharmaceutical Indicator

“…GU is the most studied TP of metformin. ,,,− The predicted no-effect concentration of 0.16 mg/L for GU derived from multiple tests with algae, daphnia, and fish was much lower than that for metformin (1 mg/L) . GU was also found to induce a low immobilization effect toward Daphnia magna with a half-maximal effective concentration (EC 50 ) of 40 mg/L and slight weight loss and increased cellular response in the hepatopancreas tissue for Planorbarius corneus at 100 mg/L .…”

“…35,91 Likewise, GU could cause a significant decline in length and weight and alter some important pathways of metabolites, proteins, and genes in the growth of 28-day-old Japanese medaka at a low concentration of 1−100 ng/L. 36,92 These results show that GU could induce adverse effects, to a greater degree than metformin, in organisms at environmental concentrations. Thus, the biological transformation of metformin to GU and the ecotoxicity of GU require more attention and extensive investigations.…”

Environmental Metabolomics Promises and Achievements in the Field of Aquatic Ecotoxicology: Viewed through the Pharmaceutical Lens

“…For instance, our previous findings led to a hypothesis on carbamazepine MeOA through autophagy induction in M. galloprovin-cialis (as in humans) via inositol depletion or endoplasmic reticulum stress [23]. Similarly, Ussery et al, applied a multi-omics approach (metabolomics and proteomics) and thereby obtained further evidence on the impact of the MeOA of guanylurea (metformin degradation product) on the early life stages of Japanese medaka [32]. After 28-day exposure at 1 ng/L concentration, they suggested that guanylurea acts by a MeOA similar to that of metformin, i.e., by activation of the AMP protein kinase (AMPK), as supported by the modulation of acetyl-CoA carboxylase 2 and alteration of the fatty acid abundance (e.g., stearic and pantothenic acid) downstream of AMPK.…”

“…The 100 µg/L threshold was chosen as the upper environmental concentration, likely to occur in areas of the world where wastewater is untreated, whereas the most common concentrations in fresh or marine waters tend to be less than 1 µg/L [18,19]. Finally, 16 articles published between 2014 and 2022 were selected [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]. Substantial information was extracted from each of them and is summarized in Table S1, such as the studied PhAC and its therapeutic class, the exposure conditions (time and concentrations), the studied organism and its sex, the sample type (e.g., organ, whole organism, and biofluide), and the analytical method used (e.g., mass spectrometry combined with liquid or gas chromatography (LC/GC-MS), and protonic nuclear magnetic resonance spectroscopy ( 1 H NMR)), and significantly modulated metabolites and their associated metabolic pathways.…”

“…Hence, the combined use of metabolomics and other omics approaches (i.e., genomics, transcriptomics, and proteomics) is a key strategy for in-depth exploration of the MeOA of PhACs and other contaminants [39]. Studies already carried out using this strategy have demonstrated its high potential in this field [23,32,34]. In a previous study, we used both metabolomics and proteogenomics approaches to assess M. galloprovincialis digestive gland samples, and obtained very complementary information on the effects of carbamazepine (3-day exposure; 0.08 and 8 µg/L concentrations) on these mussels [23].…”