Oxidative stress as a potential mechanism by which guanylurea disrupts the embryogenesis of Danio rerio.

Abstract

Metformin is one the most prescribed drug to treat type 2 diabetes. In wastewater treatment plants, this drug is bacterially transformed to guanylurea, which occurs at higher concentrations in the aquatic environments than its parent compound. Since there is a huge knowledge gap about the toxicity of this metabolite on aquatic organ- isms, we aimed to investigate the impact of guanylurea on the embryonic development and oxidative stress bio- markers of zebra!sh (Danio rerio). For this effect, zebra!sh embryos (4 h post fertilization) were exposed to 25, 50, 100, 200, 250, 25,000, 50,000, 75,000 !g/L guanylurea until 96 h post fertilization. Guanylurea led to a signif- icant delay in the hatching process in all exposure groups. Furthermore, this transformation product affected the embryonic development of !sh, inducing severe body alterations and consequently leading to their death. The most pronounced malformations were malformation of tail, scoliosis, pericardial edema, yolk deformation and craniofacial malformation. Concerning oxidative stress response, we demonstrated that guanylurea induced the antioxidant activity of superoxide dismutase, catalase, and glutathione peroxidase in zebra!sh embryos. In addition, the levels of lipid peroxidation, protein carbonyl and hydroperoxide content were also increased in the embryos exposed to this transformation product. However, the integrated biomarker response (IBR) analysis carried out in this study demonstrated that oxidative damage biomarkers got more in"uence over the embryos than antioxidant enzymes. Thus, we can conclude that guanylurea induces oxidative stress in zebra!sh embryos, and that this transformation product impair the normal development of this freshwater organism.