Multi-level biomarker responses in the marine mussel Mytilus galloprovincialis exposed to a mixture of Dexamethasone and Acetylsalicylic Acid

The increasing prevalence of pharmaceutical residues in coastal ecosystems represents a critical challenge for the health of marine organisms, which are frequently exposed to complex contaminant mixtures. This study investigated the toxicological effects of single and combined exposure to Acetylsalicylic Acid (ASA, 0.1 μg/L) and Dexamethasone (DESA, 4 ng/L) in the marine bivalve Mytilus galloprovincialis over a 14-day period. A multi-tier approach was adopted, integrating transcriptional expression, biochemical markers, and histopathological analysis. Due to the functional relevance of the target tissues, molecular and biochemical responses were assessed in pooled gill and digestive gland samples, while structural alterations were evaluated separately via histology. Individual exposures triggered moderate antioxidant responses and localized molecular shifts; however, combined ASA + DESA exposure resulted in pronounced alterations. This group was characterized by a coordinated modulation of detoxification-related genes ( abcb, cyp4y1 ), a reduction in Total Antioxidant Capacity (TAC), and changes in the expression of genes associated with apoptotic processes ( casp-2 and casp-8 ). These biochemical shifts were associated with structural changes, including lamellar hyperplasia in the gills and tubular atrophy in the digestive gland. Principal Component Analysis (PCA) confirmed that the co-exposure group represents a distinct toxicological phenotype, primarily driven by lipid peroxidation and markers of metabolic strain. While further research is needed to formally define the nature of the interaction, these findings indicate that the combined presence of non-steroidal anti-inflammatory drugs and glucocorticoids can significantly alter the physiological homeostasis of marine mussels. The study underscores the importance of considering the cumulative impact of pharmaceutical cocktails in environmental risk assessments for coastal environments.