Changes in Function and Expression Level of Multidrug Resistance-Associated Protein during Intestinal Ischemia/Reperfusion
Journal Title: Scholars Academic Journal of Pharmacy - Year 2018, Vol 7, Issue 2
Abstract
Abstract: Ischemic bowel disease is induced by poor circulation of blood, and thus oxygen and nutrition necessary for the small intestine are not supplied enough. As a result, such condition causes inflammation and ulcers, such as ischemic colitis and acute mesenteric arterial occlusion. We previously reported changes in function and expression level of P-glycoprotein (P-gp) which is a typical and important ABC transporter in the small intestine, liver and kidney during intestinal ischemia/reperfusion (I/R). In this study, we examined I/R-induced changes in multidrug resistance-associated proteins (Mrps) which is also an important ABC transporter like P-gp. The superior mesenteric vein and artery in rat were occluded by hanging itself using surgical-sutures connected with the spring balance for 60 min, followed by a reperfusion. The excretion clearances to jejunal lumen (CLjejunum), bile (CLbile) and urine (CLurine) of 5(6)-carboxyfluorescein (5-CF) diacetate (5-CFDA), a Mrp substrate, were determined after i.v. administration of 5-CFDA. We also investigated changes in the protein and mRNA expression levels of Mrp2 during intestinal I/R. It was shown that the expression behavior of Mrp2 is different depending on each organ during intestinal I/R. For the function of Mrp, during early term of reperfusion, the total clearance (CLtot) of 5-CFDA (5-CF) was significantly decreased by intestinal ischemia compared with the control condition. However, the behavior of excretion clearance was differ depending on each organ. In longer term of reperfusion, CLtot of 5-CFDA (5-CF) of intestinal I/R condition was converged to the control level until 24 hr after reperfusion. Intestinal I/R change the function and expression level of intestinal Mrp2 as well as hepatic and renal Mrp2. Therefore, when performing drug therapy to the ischemic bowel disease, the caution is necessary for the dosing of Mrp2 substrates.
Authors and Affiliations
Yusuke Takizawa, Nasa Sakamoto, Yoshifusa Tobe, Masahiro Hayashi
Keywords
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