Biochemical Marker Assessment of Chronic Carbamazepine Exposure at Environmentally Relevant Concentrations in Juvenile Common Carp (Cyprinus carpio)

Abstract

Worldwide, the anticonvulsant drug carbamazepine (CBZ) is the most frequently identified pharmaceutical residue detected in rivers. Reported chronic effects of CBZ in non-target freshwater organisms, particularly fish, include oxidative stress and damage to liver tissues. Studies on CBZ effects in fish are mostly limited to zebrafish and rainbow trout studies. Furthermore, there are only a few chronic CBZ studies using near environmental concentrations. In this study, we provide data on subacute effects of CBZ exposure (28 days) to common carp (Cyprinus carpio), employing a set of biochemical markers of damage and exposure. CBZ was found to induce a significant change in the hepatic antioxidant status of fish subjected to 5 µg/L. Moreover, with increasing concentrations, enzymatic and non-enzymatic biomarkers of oxidative defence (catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), DNA strand breaks)), toxicant biotransformation (ethoxyresorufin-o-demethylase (EROD), glutathione-S-transferase (GST)), and organ and tissue damage (lactate dehydrogenase (LDH), cetylcholinesterase (AChE)) were altered. The AChE, LDH, and lipid peroxidation (LPO) results indicate the occurrence of apoptotic process activation and tissue damage after 28 days of exposure to CBZ. These findings suggest significant adverse effects of CBZ exposure to common carp at concentrations often found in surface waters.

Chronic Effects of Carbamazepine, Progesterone and Their Mixtures at Environmentally Relevant Concentrations on Biochemical Markers of Zebrafish (Danio rerio)

“…Similar to the zebrafish findings, when common carp (Cyprinus carpio) are exposed to environmentally relevant concentrations (1-100 µg/L) of CBZ, there are alterations in several enzymes related to oxidative stress (CAT, SOD, GR, DNAsb), toxicant biotransformation (EROD, GST), and organ and tissue damage (LDH, AChE). In the same study, vitellogeninlike protein levels were found to increase following CBZ exposure, supporting the assumption that CBZ may have endocrine-disrupting effects [27]. Li et al [28] demonstrated elevated lipid peroxidation in the brain tissues of rainbow trout (Oncorhynchus mykiss) accompanied by inhibition in the activity of SOD and GR, with glutathione peroxidase and CAT showing a non-linear response in the function of time, with an increase followed by a reduction in their activities after CBZ exposure.…”

“…GST did not show increased activity after the first seven days of CBZ exposure, then it increased significantly after the second and remained significantly elevated during the fourth exposure week. In previous studies, GST was also shown to increase in Cyprinus carpio , Carassius carassius, and Danio rerio after exposure to environmentally relevant concentrations (1–100 µ/L) of CBZ [ 8 , 27 , 48 ]. Regarding the effect of P4 on GST, only the lowest applied exposure concentration (1 ng/L) triggered a significant change in GST activity, most probably due to a hormetic response.…”

“…Homogenization and biochemical determinations were performed as described by Liang et al [ 27 ]. More detailed procedures are described in Supplement S1 .…”

“…All data were analyzed as described by Liang et al [ 27 ], with the exception of categorical predictor factors, which was the treatment (control, 1, 5, 50, 100 µg/L, 1, 5, 50, 100 ng/L, or MIX1, MIX2, MIX3) in this study.…”

“…As CBZ and P4 often co-occur in the environment, this study aims to evaluate their chronic toxicological effects in zebrafish ( Danio rerio ) at environmentally relevant concentrations of these compounds, individually and in binary mixtures. To determine the toxicological effects, we focused on a suite of molecular biomarkers which are widely applied in pharmaceutical toxicity studies with fish and include: the biotransformation enzymes (7-ethoxyresorufin O-deethylase (EROD), glutathione-S-transferase (GST)), antioxidant enzymes (catalase (CAT), superoxide dismutase (SOD), glutathione peroxidases (GPxSe and GPxTOT), glutathione reductase (GR)), and markers of damage (DNA strand breaks (DNAsb), lactate dehydrogenase (LDH), lipid peroxidation (LPO), and vitellogenin-like proteins (VTG)) [ 27 , 33 , 34 , 47 , 48 ]. These biomarkers were selected to screen for and identify any mechanistic effects of oxidative stress and damage, alterations in xenobiotic metabolism, nervous effects, and endocrine disruption.…”