Intestinal Ischemia-Reperfusion Increases Efflux for Uric Acid Via Paracellular Route in the Intestine, but Decreases that Via Transcellular Route Mediated by BCRP

Abstract

-Purpose. Uric acid is thought to be one of the most important antioxidants in human biological fluids. Intestinal ischemia-reperfusion (I/R) is an important factor associated with high rates of morbidity and mortality. Reactive oxygen species (ROS) are responsible for intestinal I/R injury. The aim of this study was to clarify the efflux for uric acid from the intestine after intestinal I/R. Methods. We used intestinal ischemia-reperfusion (I/R) model rats. Serosal to mucosal flux for [14 C]-uric acid was assessed by using Ussing-type diffusion chambers. BCRP/Bcrp expression was assessed by Western blot analysis. Caco-2 cells were used for a model of the intestinal epithelium, and rotenone was used as a mitochondrial dysfunction inducer. Results. Serosal to mucosal flux for uric acid was increased after intestinal I/R, and that for mannitol was also increased. Ko143, which is a BCRP inhibitor, did not affect the uric acid transport. The decreasing uric acid transport mediated by Bcrp was caused by decrease in the level of Bcrp homodimer, bridged by an S-S bond. The suppression of Bcrp S-S bond formation was associated with mitochondrial dysfunction. Moreover, BCRP S-S bond formation activity was decreased by rotenone in Caco-2 cells. Conclusions. Serosal to mucosal flux for uric acid is significantly increased via the paracelluler route, but that via the transcellular route mediated by Bcrp is decreased after intestinal I/R. The decreasing uric acid flux mediated by Bcrp is caused by suppression of Bcrp S-S bond formation. This suppression of Bcrp S-S bond formation may be related to mitochondrial dysfunction.

Fructose Intake, Serum Uric Acid, and Cardiometabolic Disorders: A Critical Review

“…Unlike ABC transporters, however, BCRP has only one N-terminal ATP-binding domain [28,29,30]. Reduced intestinal excretion of UA is often associated with polymorphisms of the BCRP gene [26] or with a lack of BCRP dimerization, which is due to oxidative stress [31,32]. …”

Urate Transport <i>via</i> Paracellular Route across Epithelial Cells

“…9,10) On the other hand, we have recently reported that the paracellular route is the major urate transport pathway across the blood-placental barrier. 11) Urate paracellular movement was also observed in avian renal proximal tubules 12) and in the rat intestine. 13) However, the detailed mechanisms for paracellular urate transport remain elusive.…”

Effect of oxidative stress on expression and function of human and rat organic anion transporting polypeptides in the liver

“…The rats were housed for at least 1 day (190-350 g in body weight). The housing conditions were the same as those described previously (Ogura et al, 2012). During the period of acclimatization, the rats were allowed free access to food and water.…”