Multixenobiotic resistance mechanism in the catfish intestine

A mechanism similar to the multidrug resistance phenomenon displayed by mammalian tumor cells has been identified in a variety of lower species, and in a variety of tissues, including the gastrointestinal tract. Xenobiotic efflux transport activity, and the location in membranes of the gastrointestinal tract luminal surfaces, indicates that P-glycoprotein (pgp) may act in modulating the bioavailability of dietary xenobiotics in aquatic animals. The objectives of this study were to investigate the dietary inducibility, depuration, and transport abilities of pgp in the catfish intestine. For this purpose, catfish underwent dietary induction with benzo(a)pyrene, β-naphthoflavone, and 3,4,3′,4′-tetrachlorobiphenyl. Plasma membrane vesicles preparations were used for protein quantitation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, western blot, and immunohistochemical detection with C219 monoclonal antibody. Transport activity was tested using [3H]-vinblastine (VBL) as a substrate. Results have shown that a catfish intestinal protein which cross-reacts with C219 antibody is inducible following dietary xenobiotic exposure, and that lower levels of this protein are still present 16 days after termination of exposure. In addition, VBL transport was shown to be ATP dependent and inhibited by verapamil. The location, function and responsiveness of pgp to dietary inducers suggest that pgp may play a role in the bioavailability and disposition of dietary xenobiotics.