Modulation of ABC efflux transporters by bioactive substances present in rocket salad varieties: relevance to their chemopreventive action and its potential as chemotherapeutic agents.

SCHIARITI LAMPROPULOS VE; CARBALLO MA; ROMA MI; SALAZAR-SANABRIA AN; LÓPEZ NIGRO MM; PERONI RN

Mendoza

Simposio; II Simposio Internacional de Medicina Traslacional; 2019

Facultades de Ciencias Médicas y de Ciencias Exactas y Naturales (UNCuyo), Facultad de Farmacia y Bioquímica (UBA) y Facultad de Medicina (Albert-Ludwigs-Universität, Friburgo, Alemania)

Introduction/ObjectiveExposure to different genotoxic agents increases the he probability of developing cancer. ATP Binding Cassette (ABC) transporters, such as P-gp, MRPs and BCRP, mediate cellular efflux of xenobiotics or endogenous waste products against concentration gradients in an active ATP-dependent manner contributing to cell detoxification. Dietary ingredients can be pharmacokinetically inhibitors or inducers of transport processes, affecting drug disposition and being responsible for multiple resistances in antineoplastic therapy development. These interactions are under-researched and the explanations of mechanisms of interactions are not certain. Expression and activity of ABC transporters could vary by dietary habits, leading to differences in bioavailability of carcinogens as for several isolated active principles found in cruciferous vegetables. This work aims to study the modulation of ABC transport proteins in vivo by Eruca and Diplotaxis rocket genera from Argentina to evaluate benefits and/or risks of diet-drug interaction.Methods and resultsAs a first screening, by the comet and micronucleus assays, we found that the chronic consumption of D. tenuifolia and E. vesicaria juice (1, 1.4 and 2 mg/kg body weight; daily by gavage during 14 days, n= 8 animals/group) in a murine model did not cause genotoxicity damage per se, but a dose-dependent antigenotoxic effect against the genotoxic cyclophosphamide-induced (Damage Index and Micronuclei frequencies p < 0.001). For both biomarkers the damage reduction was higher for wild rocket than for common rocket, probably due to the variations in phytochemical quantitative composition within species. In this sense, BCRP and MRP2 hepatic expression were increased (p < 0.01) by the oral administration of the juice, determined by inmunoblotting. Furthermore, in order to evaluate the effect on antioxidant properties, plasmatic (p