Long-term exposure of marine mussels to paracetamol: is time a healer or a killer?

Abstract

Pharmaceuticals pose a major threat to the marine environment, and several studies have recently described their negative effects on marine organisms. Pharmaceutical compounds are constantly being released into aquatic ecosystems, and chronic exposure, even at low concentrations, may have a major impact on marine organisms. The purpose of the present study is to evaluate the biological changes induced by one of the most widely used pharmaceuticals-paracetamol-in the blue mussel Mytilus edulis, after a long-term exposure at environmentally relevant concentrations. We present our data alongside and in comparison with results from a previous short-term exposure, to demonstrate the significance of exposure period on the effects of paracetamol in adult blue mussels. After 24 days of laboratory exposure, seven potential target genes were selected to examine toxicological effects in mussels' gonads and possible disruptive effects on reproductive processes. The results show the modulation of some important reproduction-related genes: estrogen receptor-2 (ER2), vitelline envelope zona pellucida domain-9 (V9), and vitellogenin (VTG). Variations in mRNA expression of four other genes involved in apoptosis (HSP70, CASP8, BCL2, and FAS) are also highlighted. Histopathological alterations caused by paracetamol, together with neutral red retention time response in mussels' hemocytes, are presented herein. Overall, this study highlights the exacerbated effects of low concentration of paracetamol after chronic exposure, similar to the damage induced by higher concentrations in a short exposure scenario, thus emphasizing the importance of length of exposure period when studying the effects of this substance. Additionally, this study also discusses the potential of paracetamol to inflict several major changes in the reproductive system of mussels and thus possibly affect the survival of populations.

Metals in green mussels: is there any effect on their reproduction? A preliminary study of Muara Angke, Jakarta Bay

“…Atresia, a degenerative process with subsequent elimination and resorption of oocytes [43], was observed as the pathology with the highest occurrence in this study. This is similar to results from several recent studies [44,45], which documented high occurrences of atresia in mussels even at low levels of paracetamol exposure. Also worth mentioning here is that the lower incidence of hemocytic infiltration and inflammatory foci compared to atresia might indicate that metal contamination is more directly related to degenerative effects than to inflammatory conditions in the mussels' reproductive organs.…”

Paracetamol (Acetaminophen) and the Developing Brain

“…Changes in development, behavior, enzyme activities, and DNA methylation patterns have been observed in zebrafish larvae and embryos exposed for several days to paracetamol at concentrations as low as 5 µg/L [91]. In small planktonic crustaceans of the genus Daphnia (water flea), paracetamol at 40 µg/L was found to alter glutathione S-transferase activity and behavior (swimming distance) [92], while sea mussels (Mytilus edulis) show altered gene expression patterns even at 40 ng/L [93]. While these observations bear little direct relevance for the developing human brain, they demonstrate that minute amounts of paracetamol may exert biological responses in evolutionary distant species.…”

Sex and gametogenesis stage are strong drivers of gene expression in Mytilus edulis exposed to environmentally relevant plasticiser levels and pH 7.7

“…Genes for superoxide dismutase ( sod ) and catalase ( cat ) were chosen as part of the antioxidant enzyme system due to their coordinated roles in reducing superoxide anion O 2 − , a reactive oxygen species (ROS, Regoli and Giuliani 2014 ). Heat shock protein 70 ( hsp70 ) was selected as a biomarker of stress responsive to environmental perturbation (Encomio and Chu 2005 ; Lewis et al 1999 ) and xenobiotic exposure (Franzellitti and Fabbri 2005 ; Koagouw et al 2021 ). Genes coding for carbonic anhydrase 2 ( CA2 ), oestrogen-related receptor (ERR, MeER1 ) and oestrogen receptor (ER, MeER2 ) were chosen as they are associated with biomineralisation, pH homeostasis and reproductive cycle, whose expression can be affected by oestrogenic compounds (Balbi et al 2016 ; Ciocan et al 2010 ; Nagasawa et al 2015 ).…”