Impact of ischemic-kidney injury on intestinal ABC transporter

BULACIO ROMINA; FUSSI M. FERNANDA; RIVABELLA MATKINS TOMAS; HAZELHOFF M. HERMINIA; CAMPAGNO ROMINA; MONASTEROLO, LILIANA A.; MOLINAS, SARA M.; LAROCCA, M. CECILIA; BRANDONI ANABEL

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias SAIC, SAFIS, SAI 2022; 2022

Sociedad Argentina de Investigación Clínica y Sociedad Argentina de Fisiología

Acute kidney injury caused by ischemia-reperfusion (IR) is a complexpathophysiological process associated with numerous metabolicand structural changes, also affecting remote organs. P-glycoprotein(P-gp, ABCB1) and Multidrug resistance-associated protein 2(Mrp2, ABCC2) belong to ATP-binding cassette (ABC) transportersuperfamily. Both are expressed in kidney and intestine at the apicalmembrane of proximal tubular cells and enterocytes, respectively.They are involved in the efflux of endogenous compounds and xenobiotics.The aim of this study was to evaluate how renal IR injuryaffects the intestinal expression of P-gp and Mrp2. Male Wistar ratswere subjected to 40 min of unilateral renal ischemia followed by 24h of reperfusion (IR, n=3). Sham-operated controls (C, n=3) werealso processed. P-gp and Mrp2 expression in total plasma membranesfrom post-ischaemic kidneys (P-gpKm and Mrp2Km) and inapical membranes from jejunum and ileum regions of small intestine(P-gpJm; P-gpIm; Mrp2Jm and Mrp2Im) were evaluated by immunoblotting.t-Student *: p < 0,05, **: p < 0,01. Results: P-gpKm (%):C=100±9, IR=163±20*; P-gpJm (%): C=100±6, IR=58±4**; P-gpIm (%):C=100±7, IR=91±7; Mrp2Km (%): C=100±9, IR=106±3; Mrp2Jm (%):C=100±11, IR=102±14; Mrp2Im (%): C=100±12, IR=171±18*. Afterrenal IR injury, P-gp expression was increased in renal membranesand decreased in apical membranes from jejunum, whereas Mrp2expression did not change in renal membranes but significantly increasedin apical membranes from ileum. In conclusion, after inducingrenal IR injury, expression of P-gp and Mrp2 is differentiallyregulated, not only in the kidney, where the insult occurs, but alsoin remote organs, such as the intestine, with region-specific alterations.Those modifications may impact on handling of P-gp andMrp2 substrates during kidney injury. The mechanisms underlyingthose alterations will be the subject of further studies.