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| Author(s): |
Filipe Guilherme Andrade de Godoi
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB) |
| Defense date: | 2025-02-12 |
| Examining board members: |
Renata Guimarães Moreira Whitton;
Helena Cristina da Silva de Assis;
Rodrigo Hernán da Cuña;
Camilo Dias Seabra Pereira
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| Advisor: | Renata Guimarães Moreira Whitton; Fabiana Laura Lo Nostro |
| Abstract | |
The Non-steroidal anti-inflammatory drugs (NSAIDs) have been detected in the aquatic compartments and studies reported adverse biological effects among non-target species. Nevertheless, the knowledge of these impacts is limited for endemic aquatic species requesting additional data related to the NSAIDs effects and occurrence across the environments. Thus, the present scientific study aims to summarize the main scientific efforts in the literature concerning the occurrence of NSAIDs in Brazilian aquatic ecosystems, and to evaluate the physiological biomarkers in the native species Astyanax lacustris after diclofenac (DCF and ibuprofen (IBU) exposure using distinct concentrations and experimental periods. Moreover, the study investigated the effect of DCF using concentrations under environmental safety threshold (Environment Quality Standard (EQS)) in the ecological endpoints and transcriptomic data of Gammarus locusta species. After the literature search, the occurrence of NSAIDs across the Brazilian waters was described in 32 studies, the majority of the effects are related to oxidative stress and endocrine related biomarkers. In the acute exposure of 24 and 96h the DCF physiological effects and toxicity of DCF and IBU isolated and mixed (MIX), using females of the native freshwater teleost Astyanax lacustris was evaluated. NSAIDs bioavailability, the results showed absence of degradation of IBU and DCF after 7 days of exposure. IBU LC50 for A. lacustris was 137 mgL-1 and females exposed to IBU isolated increased thyroxine (T4) concentration at 24h and decreased after 96h; DCF exposure decreased triiodothyronine (T3) concentration at 96h. Circulating levels of 17-estradiol (E2), cortisol (F) and testosterone (T) were not affected by any treatment. The genes fsh, pomc and vtg were upregulated after 24h of IBU exposure, and dio2 was downregulated in the DCF fish exposed group after 96h compared to the mixture. Protein concentration was reduced in muscle and increased in the liver by DCF and MIX exposures at 24h;while liver lipids were increased in the mixture groups after 96h. In the 7 days experiment, animals were exposed to group control (CTL), 14 g L-1 (DCF); 16 g L-1 (IBU); and DCF 14 + IBU 16 g L-1 (MIX). After exposure, energetic substrates (protein, glycogen and lipid content), COX activity, endocrine gene expression and hormonal profile were evaluated. The results showed that T concentration was increased in fish exposed to IBU and Prostaglandin E2 (PGE2) concentration was reduced in fish from DCF and MIX groups. No changes were observed in the concentration of 17-estradiol (E2), cortisol (F), triiodothyronine (T3) and thyroxine (T4). Total COX activity, glycogen and protein content were not altered among the treatments compared to CTL, but hepatic lipid concentration was reduced in MIX. Also, dio2 was upregulated and pomc gene expression were downregulated after DCF exposure compared to CTL, but expression of lh, tsh, fsh remained unchanged. In the G. locusta exposure, the study investigated the ecological endpoints (survival, reproduction and growth) and molecular responses (gene transcription) of G. locusta parental generation (F0) exposed to nominal concentrations (0.05, 0.25,1.25, 6.25 ugL-1) of DCF. Given the findings of the first directly exposed generation (F0), the ecological endpoints in the subsequent non-exposed generations (F1) were also evaluated. In the F0 generation, there was a significant marginal reduction of fertility in the 1.25 ugL-1 treatment after 51 days of exposure and an increase in the 0.05 ugL-1 treatment compared to control. However, most ecological endpoints including survival, number of ovigerous females, growth, and sex ratio were not affected in either of the generations. Interestingly, despite the absence of marked effects in ecological endpoints, Transcriptomic analysis showed a total of 677 differentially expressed genes in the 0.05 ugL-1 treatment (EQS) which includes main endocrine and metabolic pathways as molting hormone, tyrosine metabolism. In summary, occurrences of NSAIDs have been elucidated in the Brazilian territory with distinct biological effects to native aquatic organisms. Additionally, the present study suggests that A. lacustris females display physiological changes according to concentrations in the exposures and experimental periods showing the NSAIDs impact in non-target organisms. Moreover, despite the marginal effects in the apical endpoints of G. locusta, the application of the transcriptome showed molecular alterations suggesting that sensitive species could be more susceptible and, therefore, future directions on NSAIDs investigations are requested using an integrative approach between environmental safety standards and human health at different environmental risk evaluations. (AU) | |
| FAPESP's process: | 20/01527-6 - Neuroendocrine and metabolic adjustments in the hypothalamic-pituitary-gonadal, interrenal and thyroid axes in Astyanax altiparanae females (Characiformes: Characidae) exposed to anti-inflammatory drugs |
| Grantee: | Filipe Guilherme Andrade de Godoi |
| Support Opportunities: | Scholarships in Brazil - Doctorate |