Effects of blood lipid lowering pharmaceuticals (bezafibrate and gemfibrozil) on immune and digestive gland functions of the bivalve mollusc, Mytilus galloprovincialis

Abstract

Fibrates are hypolipidemic pharmaceuticals that have been detected as contaminants in wastewaters and surface waters. In this work, the possible effects of two fibrates, Bezafibrate (BEZA) and Gemfibrozil (GEM) in the bivalve mollusc Mytilus spp were investigated. In the immune cells, the hemocytes, addition of both compounds in vitro induced rapid lysosomal membrane destabilization, extracellular lysozyme release, NO production and decreased phagocytic activity. The effect of fibrates were partly mediated by activation of ERK and p38 MAPKs (Mitogen Activated Protein Kinases), as demonstrated by the use of specific inhibitors of different kinases. The effects of fibrates on hemocyte function were confirmed in vivo, in the hemocytes of mussels injected with 0.01, 0.1 and 1 nmol/animal (corresponding to nominal concentrations of 3.61, 36.18 and 361.8 ng/g dry weight for BEZA and of 2.50, 25.03 and 250.35 ng/g dry weight for GEM, respectively) and sampled at 24 h post-injection. Both compounds induced a concentration-dependent lysosomal destabilization and extracellular lysozyme release; an increase in phagocytosis was observed at the highest concentration. In vivo exposure to fibrates also induced significant effects on mussel digestive gland, the key metabolic organ in bivalves. Both BEZA and GEM increased the activity of the glycolytic enzymes phosphofructokinase (PFK) and pyruvate kinase (PK), and of Glutathione transferase (GST) glutathione reductase (GSR), and total glutathione content. A significant increase in the peroxisomal enzyme catalase was observed; however, BEZA exposure decreased Palmytoyl CoA oxidase activity, whereas GEM was ineffective. The results indicate that in mussels environmental concentrations of hypolipidemic drugs can affect the immune function, as well as glycolysis, redox balance and peroxisomal function.