• Fructose-enriched diet decreases protein expression and activity of intestinal Mrp2.

ZECCHINATI, FELIPE; TOCCHETTI, GUILLERMO NICOLÁS; BARRANCO, MARIA MANUELA; DOMÍNGUEZ, CAMILA JULIANA; ARANA, MAITE ROCÍO; MOTTINO, ALDO DOMINGO; GARCÍA, FABIANA; VILLANUEVA, SILVINA STELLA MARIS

MAR DE PLATA

Congreso; REUNIÓN CONJUNTA SAIC SAI SAFIS 2018; 2018

Increased intake of fructose in humans and laboratory rodents isknown to be a risk factor for the development of metabolic disordersas insulin resistance, metabolic syndrome (MS) and type 2 diabetesas well as cardiovascular diseases. Mrp2 and phase II biotransfor- mation enzymes, acting as intestinal biochemical barriers, strongly infuence the bioavailability, and hence the effcacy and safety, of orally administered drugs. Aim: to evaluate the effect of the chronic administration of 10% fructose (F) in drinking water to male Wistar rats for 8 weeks on jejunal Mrp2 expression, by western blot, and on its activity, by using the everted intestinal sacs model. Control rats(C) received tap water. Results: fructose consumption led to high plasma triglycerides and insulin levels, as well as insulin resistance and glucose intolerance in F vs C (p0.05). A signifcant decrease in Mrp2 protein expression was observed in F (-80%) respect to C (p0.05). This result correlated with the decrease of serosal-to-mu- cosal transport of the Mrp2 substrate dinitrophenyl-S-glutathione (DNP-SG), generated from its precursor 1-chloro-2,4-dinitroben- zene (CDNB) (F:-30% respect to C, p0.05). Cytosolic GST activity involved in the conversion of CDNB to DNP-SG, was also reduced by the treatment (F:-14% respect to C, p0.05). This result correlat- ed with a signifcant decreased in GSTa expression in F rats (-43%) respect to C. Moreover, fructose administration induced alterations in parameters of oxidative stress by decreasing both the activity of antioxidant enzyme superoxide dismutase (-34%, p0.05) and the GSH/GSSG ratio (-39% p0.05), as well as an increased of lipid peroxidation end products (+130% p