Health impact assessment after Danio rerio long-term exposure to environmentally relevant concentrations of metformin and guanylurea

Abstract

The antidiabetic drug metformin (MET) and its metabolite guanylurea (GUA) have been frequently and ubiquitously detected in surface water. Consequently, there has been a consistent rise in studying the toxicity of MET and GUA in fish over the past decade. Nonetheless, it is noteworthy that no study has assessed the harmful effects both compounds might trigger on fish blood and organs after chronic exposure. Taking into consideration the data above, our research strived to accomplish two primary objectives: Firstly, to assess the effect of comparable concentrations of MET and GUA (1, 40, 100 μg/L) on the liver, gills, gut, and brain of Danio rerio after six months of flow-through exposure. Secondly, to compare the outcomes to identify which compound prompts more significant oxidative stress and apoptosis in organs and blood parameter alterations. Herein, findings indicate that both compounds induced oxidative damage and increased the expression of genes associated with apoptosis (bax, bcl2, p53, and casp3). Chronic exposure to MET and GUA also generated fluctuations in glucose, creatinine, phosphorus, liver enzymes, red and white blood count, hemoglobin, and hematocrit levels. The observed biochemical changes indicate that MET and GUA are responsible for inducing hepatic damage in fish, whereas hematological alterations suggest that both compounds cause anemia. Considering GUA altered to a more considerable extent the values of all endpoints compared to the control group, it is suggested transformation product GUA is more toxic than MET. Moreover, based on the above evidence, it can be inferred that a six-month exposure to MET and GUA can impair REDOX status and generate apoptosis in fish, adversely affecting their essential organs' functioning.