Inhibition of multixenobiotic resistance mechanism in aquatic organisms by commercially used pesticides

Mechanism of multixenobiotic resistance (MXR), mediated by expression of the transmembrane P-glycoprotein, represents a basic biological defence system in aquatic organisms. However, this defence is very sensitive to the presence of different inhibitors present in many environmental pollutants, microbial products, or extracts from polluted river and marine water. Recently, interactions between P-glycoprotein and pesticides have also been reported. This possibility directed us to assess the MXR inhibitory potential of pesticides. Using both the in vitro (cell culture) and the in vivo (mussel Dreissena polymorpha) method, we tested 16 pesticides representing several chemical classes that are used commercially in Croatia. We also investigated the MXR modulating effect of binary combinations of pesticides, and classified observed effects as antagonism, additivity or synergism. Our results clearly demonstrate that several pesticides, in concentrations far below officially established LD50 values for fish, exhibit a strong MXR inhibitory effect. The presence of these chemosensitizing pesticides in the environment could enhance the accumulation and toxic effects of other xenobiotics.