Effects of Water Temperature Increase on Transcriptomic, Biochemical, and Histopathological Responses of the Bivalve Species Mytilus Galloprovincialis to the Antineoplastic Drug  5-Fluorouracil

Abstract

The present study aimed to assess the potential ecotoxicological effects of 5-fluorouracil (5-FU), an antineoplastic already found in aquatic ecosystems, towards the bivalve Mytilus galloprovincialis, considering actual and warming temperature scenarios. To this end, organisms were exposed for 28 days to increasing 5-FU concentrations (10, 100, and 500 ng/L) at control (17 ± 1.0 °C) and warming (21 ± 1.0 °C) temperatures. Transcriptomic of selected target genes, biochemical responses, and histopathological alterations were used to assess possible detrimental effects. Results showed an overall down-regulation of mRNA transcripts related to xenobiotic metabolization pathways and cell apoptosis in organisms exposed to 5-FU, especially at 21 ºC. While at 17 ºC, the antioxidant defenses were not enough to avoid cell damage caused by 5-FU, at 21 ºC the metabolic slowdown avoided further cell damage. However, histopathological alterations in the digestive gland at 21 ºC and high concentrations of 5-FU were observed. Overall, the present results indicate that the warming temperature may enhance the detrimental effects of 5-FU on this species, with metabolism being particularly affected.

Keywords: Anticancer drugs, Bivalves, climate change, Gene expression, Oxidative stress