Salinity Influence on Mytilus galloprovincialis Exposed to Antineoplastic Agents: A Transcriptomic, Biochemical, and Histopathological Approach.

Nowadays, aquatic species face a variety of environmental risks associated with pharmaceutical consumption. More specifically, the increased number of cancer patients has been accompanied by an increased consumption of antineoplastic drugs, such as ifosfamide (IF) and cyclophosphamide (CP). These drugs have been found in aquatic ecosystems, raising concerns about their impact, especially on estuarine species, as marine waters are the final recipients of continental effluents. Simultaneously, organisms may be threatened by predicted climatic changes, such as salinity shifts. Considering this, the present research intends to investigate the combined effects of IF and CP, and salinity shifts. For this, a transcriptomic, biochemical, and histopathological assessment was made using the bivalve species Mytilus galloprovincialis exposed for 28 days to IF and CP (500 ng/L), individually, at different salinity levels (20, 30, and 40). IF and CP up-regulated metabolism-related gene cyp3a1, with CP also affecting abcc gene, showing minimal salinity impact and highlighting the importance of these metabolic routes in mussels. Salinity shifts affected the transcription of genes related to apoptosis and cell cycle growth, such as p53, as well as the aerobic metabolism (ETS), the antioxidant (CAT, SOD, GSH) and biotransformation mechanisms (GST activity). These findings indicate mussels' high metabolic adaptability to osmotic stress. Under CP exposure and low salinity, mussels exhibited increased LPO levels and histopathological effects in digestive gland tubules, revealing detrimental effects towards M. galloprovincialis, and suggesting that a metabolic slowdown and activation of antioxidant mechanisms helped prevent cellular damage at control and high salinities. Overall, results reinforce the need for antineoplastics ecotoxicological risk assessment, especially under foreseen climate change scenarios.

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Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☐ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests