INTESTINAL MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 2 (MRP2) IS DOWNREGULATED BY OXIDATIVE STRESS (OS) VIA A POSTTRANSLATIONAL MECHANISM. IMPACT ON ITS MEMBRANE BARRIER FUNCTION

ZECCHINATI, FELIPE; BARRANCO, MARÍA M.; TOCCHETTI, GUILLERMO N.; DOMINGUEZ, CAMILA J.; ARANA, MAITE R.; PERDOMO, VIRGINIA; LUQUITA, MARCELO G.; VIGNADUZZO, SILVANA; MOTTINO, ALDO D.; GARCÍA, FABIANA; VILLANUEVA, SILVINA S. M.

REUNIÓN VIRTUAL

Congreso; SOCIEDAD ARGENTINA DE FISIOLOGÍA (SAFIS) 2020; 2020

The intestinal tract is a major site of pro-oxidant agent?s production, as a resultof continuous exposure to food additives and contaminants. Homeostaticcontrol of intestinal oxidative environment is crucial in nutrient digestion andabsorption, and barrier function. Intestinal Mrp2 is an ABC transporter that limitsthe absorption of xenobiotics orally ingested, thus acting as a biochemicalbarrier. We here evaluated the short-term effect of OS on intestinal Mrp2subcellular localization and its barrier function by treatment of isolated intestinalsacs with 250 μM of tert-butyl hydroperoxide (TBH 250) for 30 min (N=6). Wefirst confirmed that TBH 250 generated OS in intestinal tissue as indicated byincreasing lipid peroxidation products (+61%) and catalase (+44%) andglutathione peroxidase (+28%) activities, and by decreasing GSH content (-19%), the GSH/ GSSG ratio (-29%) and superoxide dismutase activity (-21%),respect to controls (C, p