Microcystin-LR modulates multixenobiotic resistance proteins in the middle intestine of rainbow trout, Oncorhynchus mykiss

PAINEFILÚ, J.C.; GONZÁLEZ, C.; CÁRCAMO J.G.; BIANCHI V.A.; LUQUET C.M

AQUATIC TOXICOLOGY

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2022 vol. 253

0166-445X

Global climate change favors explosive population growth events (blooms) of phytoplanktonic species, oftenproducing toxic products, e.g., several genera of cyanobacteria synthesize a family of cyanotoxins calledmicrocystins (MCs). Freshwater fish such as the rainbow trout Oncorhynchus mykiss can uptake MCs accumulatedin the food chain. We studied the toxic effects and modulation of the activity and expression of multixenobioticresistance proteins (ABCC transporters and the enzyme glutathione S-transferase (GST) in the O. mykiss middleintestine by microcystin-LR (MCLR). Juvenile fish were fed with MCLR incorporated in the food every 12 h andeuthanized at 12, 24, or 48 h. We estimated the ABCC-mediated transport in ex vivo intestinal strips to estimateABCC-mediated transport activity. We measured total and reduced (GSH) glutathione contents and GST andglutathione reductase (GR) activities. We studied MCLR cytotoxicity by measuring protein phosphatase 1 (PP1)activity and lysosomal membrane stability. Finally, we examined the relationship between ROS production andlysosomal membrane stability through in vitro experiments. Dietary MCLR had a time-dependent effect on ABCCmediatedtransport, from inhibition at 12 h to a significant increase after 48 h. GST activity decreased only at 12h, and GR activity only increased at 48 h. There were no effects on GSH or total glutathione contents. MCLRinhibited PP1 activity and diminished the lysosomal membrane stability at the three experimental times. In the invitro study, the lysosomal membrane stability decreased in a concentration-dependent fashion from 0 to 5 μmol L􀀀 1 MCLR, while ROS production increased only at 5 μmol L 􀀀 1 MCLR. MCLR did not affect mRNA expression ofabcc2 or gst-π. We conclude that MCLR modulates ABCC-mediated transport activity in O. mykiss’s middle intestinein a time-dependent manner. The transport rate increase does not impair MCLR cytotoxic effects.