Reversion of down-regulation of intestinal multidrug resistance-associated protein 2 in fructose-fed rats by geraniol and vitamin C. Potential role of inflammatory response and oxidative stress

ZECCHINATI, F; BARRANCO, MM; ARANA, NULL; TOCCHETTI, GN; DOMÍNGUEZ, CJ; PERDOMO, VG; RUIZ, ML; MOTTINO, AD; GARCÍA, F; VILLANUEVA, SSM

JOURNAL OF NUTRITIONAL BIOCHEMISTRY

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2019

0955-2863

Intestinal multidrug resistance-associated protein 2 is an ABC transporter thatlimits the absorption of xenobiotics ingested orally, thus acting as essential componentof the intestinal biochemical barrier. Metabolic Syndrome (MetS) is a pathologicalcondition characterized by dyslipidemia, hyperinsulinemia, insulin resistance, chronicinflammation, and oxidative stress (OS). In a previous study we demonstrated thatMetS-like conditions induced by fructose in drinking water (10% v/v, during 21 days),significantly reduced the expression and activity of intestinal Mrp2 in rats. We hereevaluated the potential beneficial effect of geraniol or vitamin C supplementation,natural compounds with anti-inflammatory and anti-oxidant properties, in reversefructose-induced Mrp2 alterations. After MetS-like conditions were induced (21 days),animals were cotreated with geraniol or vitamin C or vehicle for another 14 days.Decreased expression of Mrp2 protein and mRNA due to fructose administration wasreversed by geraniol and by vitamin C, consistent with restoration of Mrp2 activityevaluated in everted intestinal sacs. Concomitantly, increased intestinal IL-1β and IL-6levels induced by fructose were totally and partially counterbalanced, respectively, bygeraniol administration. The intestinal redox unbalance generated by fructose wasimproved by geraniol and vitamin C, as evidenced by decreasing lipid peroxidationproducts and activity of Superoxide Dismutase and by normalizing glutathionereduced/oxidized glutathione ratio. The restoration effects exhibited by geraniol andvitamin C suggest that local inflammatory response and OS generated under MetS-likeconditions represent important mediators of the intestinal Mrp2 down-regulation.Additionally, both agents could be considered of potential therapeutic value to preserveMrp2 function under MetS conditions