ABSTRACT:In the present study, the effects of sub-lethal sub-chronic doses of ibuprofen, diclofenac, and carbamazepine alone, and in combination (concentration range 0.02-60 µg/l), on the early life stages of tench (Tinca tinca) were investigated. The lower concentrations of pharmaceuticals tested (0.02, 0.2, 2 µg/l) represent the concentration values of these substances commonly present in surface waters or effluents from wastewater treatment plants. Multiple biomarkers of biotransformation, antioxidant defence systems, and lipid peroxidation were determined in fish after 35 days of exposure. The evaluated pharmaceuticals induced oxidative stress in fish both alone and in combination with each other. Generally, 60 µg/l of each single pharmaceutical influenced the activity of antioxidant enzymes significantly (P < 0.05), whereas the same concentration of these pharmaceuticals in combination (1 : 1 : 1) did not have any impact on the activity of these enzymes. However, changes in biotransformation and antioxidant enzymes were apparent if lower concentrations of these pharmaceuticals were administered in the mixture. Significant changes (P < 0.05) in the activities of glutathione reductase, glutathione peroxidase, and glutathione-S-transferase were observed even at environmental concentration ranges. A significant effect (P < 0.05) on lipid peroxidation levels was found only in the experimental group exposed to carbamazepine.
Keywords: antioxidant defence system; lipid peroxidationList of abbreviations ANC = acid-neutralising capacity, CAT = catalase, CBZ = carbamazepine, COD Mn = chemical oxygen demand, COX = cyclooxygenase, DCF = diclofenac, DMSO = dimethylsulfoxide, GPx = glutathione peroxidase, GR = glutathione reductase, GSH = reduced active form of glutathione, GSSG = oxidised inactive form of glutathione, GST = glutathione-S-transferase, IBU = ibuprofen, LC = liquid chromatography, LC-MS/MS = liquid chromatography with tandem mass spectrometry, LPO = lipid peroxidation level, NSAIDs = non-steroidal anti-inflammatory drugs, ROS = reactive oxygen species Pharmaceutical mixtures that contaminate water sources are currently a problem worldwide. Ibuprofen (IBU), diclofenac (DCF), and carbamazepine (CBZ) are among the most frequently detected drugs in aquatic ecosystems. Their concentrations in surface water range from ng/l to tens of µg/l. Higher concentrations have been detected in developing countries due to the direct discharge of untreated wastewater from residences and hospitals into surface waters (Tran et al. 2014).