Multilevel assessment of carbamazepine effects: An integrative approach using zebrafish early-life stages.

Autor: Silva, Muriel Lopes da1 (AUTHOR), Andrade, Thayres Sousa2 (AUTHOR), Villacis, Rolando André Rios1 (AUTHOR), Sousa-Moura, Diego1 (AUTHOR), Domingues, Inês3 (AUTHOR), Lisboa, Carolina Almeida1 (AUTHOR), Camargo, Níchollas Serafim1 (AUTHOR), Pic-Taylor, Aline1 (AUTHOR), Oliveira, Rhaul de4 (AUTHOR), Grisolia, Cesar Koppe1 (AUTHOR) grisolia@unb.br
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Zdroj: Chemosphere. May2024, Vol. 355, pN.PAG-N.PAG. 1p.
Abstrakt: Carbamazepine (CBZ) is the most commonly used drug in epilepsy treatment, and its metabolites are commonly detected among persistent pharmaceuticals in the aquatic environment. This study aimed to investigate CBZ effects on early-life-stage zebrafish (Danio rerio) (from 2 to 168 hpf) by employing of an integrative approach linking endpoints from molecular to individual level: (i) development; (ii) locomotor activity; (iii) biochemical markers (lactate dehydrogenase, glutathione-S-transferase, acetylcholinesterase and catalase) and (iv) transcriptome analysis using microarray. A 168 h - LC 50 of 73.4 mg L−1 and a 72 h - EC 50 of 66.8 mg L−1 for hatching were calculated while developmental effects (oedemas and tail deformities) were observed at CBZ concentrations above 37.3 mg L−1. At the biochemical level, AChE activity proved to be the most sensitive parameter, as evidenced by its decrease across all concentrations tested (∼25% maximum reduction, LOEC (lowest observed effect concentration) < 0.6 μg L−1). Locomotor behaviour seemed to be depressed by CBZ although this effect was only evident at the highest concentration tested (50 mg L−1). Molecular analysis revealed a dose-dependent effect of CBZ on gene expression. Although only 25 genes were deregulated in organisms exposed to CBZ when compared to controls, both 0.6 and 2812 μg L−1 treatments impaired gene expression related to development (e.g. crygmxl1 , org , klf2a , otos , stx16 and tob2) and the nervous system (e.g. Rtn3 , Gdf10 , Rtn3), while activated genes were associated with behavioural response (e.g. prlbr and taar). Altogether, our results indicate that environmentally relevant CBZ concentrations might affect biochemical and genetic traits of fish. Thus, the environmental risk of CBZ cannot be neglected, especially in a realistic scenario of constant input of domestic effluents into aquatic systems. [Display omitted] • Carbamazepine toxicity was evaluated at different biological levels. • Developmental anomalies were detected at concentrations above 37.3 mg L−1. • Acetylcholinesterase activity was inhibited suggesting neurotoxicity. • Analysis of gene expression identified alterations in diverse functional categories. • Down regulated genes were linked with phenotypic and behavioural responses. [ABSTRACT FROM AUTHOR]
Databáze: GreenFILE