Effects of a chronic exposure to gemfibrozil in Carassius auratus

Lipid regulators, such as fibrates, are pharmaceuticals manufactured to treat dyslipidaemias in humans. Their constant use and discard combined to their environmental persistence and poor removal rates from wastewater makes of these emergent contaminants ubiquitous in aquatic systems, with gemfibrozil (GEM) being the most commonly detected fibrate in water. The present study aimed to describe the effects of a 28day waterborne exposure to both an environmentally relevant concentration (1.5 µg/L) and a spiked concentration (15 mg/L) of GEM, in adult individuals of the model organism Carassius auratus (goldfish). To this end, bioaccumulation of this compound in liver and muscle, as well as variations on haematological parameters, plasma biochemistry endpoints, and the expression of relevant target genes in the liver were investigated. The results indicated that, following exposure to the highest concentration of GEM, this compound accumulated in both liver and muscle. Similarly, significant increases were observed in haemoglobin levels, and mean corpuscular haemoglobin concentrations in individuals exposed to 15 mg/L of GEM. The biochemical profiling of plasma revealed significant decreases of cortisol and glucose levels, as well as a significant increase in the total antioxidant capacity (TAC) together with significant upregulations of gene transcripts related to antioxidant defences (gpx, gst) and lipid metabolism (apoa1). However, no changes were observed between treatments in the relative expression of key pro-inflammatory markers (il1β, il6 and il8) nor genetic markers of lipid metabolism (pparα pparβ and pparγ) or plasma levels of cholesterol and triglycerides. Overall, the results suggest that bioaccumulation of GEM in C. auratus triggers mild antioxidant responses at high doses but not at environmentally relevant ones.