Combined effects of a pharmaceutical pollutant, gemfibrozil, and abiotic stressors (warming and air exposure) on cellular stress responses of the blue mussels Mytilus edulis

Lipid-lowering drugs such as gemfibrozil (GFB) are widely used and highly biologically active, contributing to their persistence in wastewater and subsequent release into aquatic ecosystems. However, the potential impacts and toxic mechanisms of these emerging pollutants on non-target marine organisms, particularly keystone bivalves like Mytilus edulis, remain poorly understood. To address this knowledge gap, we investigated the effects of environmentally relevant concentrations of GFB (25 µg l⁻¹) on oxidative, nitrosative, and dicarbonyl stress in M. edulis, and explored how abiotic stressors such as elevated temperature and air exposure modulate these effects. Our results indicated that GFB and temperature interact to significantly influence oxidative stress markers, including lipid peroxidation (LPO) and protein carbonylation (PC) levels in mussels. Notably, the combination of GFB and warming exhibited antagonistic effects, leading to reduced LPO levels in both submerged and air-exposed mussels. Air exposure alone elevated PC levels across all groups, while warming reduced these levels. Total antioxidant capacity increased during air exposure, with GFB exerting minimal influence on this parameter. Nitrosative stress, as indicated by nitric oxide levels, was significantly affected by GFB only under air exposure conditions. The glutathione system underwent notable alterations, with glutathione reductase activity stimulated during immersion and suppressed during air exposure. Dicarbonyl stress markers, including methylglyoxal and glyoxalase enzyme activities, generally intensified in response to GFB during air exposure. Overall, environmentally relevant concentrations of GFB induced oxidative and dicarbonyl stress in M. edulis, suggesting a shift toward glycolytic metabolism that could impair energy-dependent processes like reproduction. Combined stressor scenarios involving GFB and warming typically exhibited antagonistic rather than synergistic effects. Despite these biochemical disruptions, the mussels demonstrated resilience, particularly during air exposure, highlighting the complexity of environmental stress interactions. These findings emphasize the importance of considering multiple stressors in pollution risk assessments for aquatic ecosystems.