Oat1/3 Restoration Protects against Renal Damage after Ischemic AKI.

Oat1/3 Restoration Protects against Renal Damage after Ischemic AKI. Am J Physiol Renal Physiol. 2014 Nov 12;:ajprenal.00160.2014 Authors: Schneider R, Meusel M, Betz B, Held C, Möller-Ehrlich K, Büttner-Herold M, Wanner C, Gekle M, Sauvant C Abstract Expression of proximal tubular organic anion transporters Oat1 and Oat3 is reduced by prostaglandin E2 (PGE2) after renal ischemia and reperfusion (I/R) injury. We hypothesized that impaired expression of Oat1/3 is decisively involved in deterioration of renal function after I/R injury. Therefore, we administered probenecid, which blocks proximal tubular indomethacin uptake, to abolish indomethacin mediated restoration of Oat1/3 regulation and its effect on renal functional and morphological outcome. Ischemic AKI was induced in rats by bilateral clamping of renal arteries for 45 min with 24h follow up. Low-dose indomethacin (1mg/kg) was given i.p. at the end of ischemia. Probenecid (50mg/kg) was administered i.p. 20 min later. Indomethacin restored Oat1/3 expression, PAH net secretion and PGE2 clearance and improved kidney function as measured by GFR, renal perfusion as determined by corrected PAH clearance and morphology, whereas it reduced renal cortical apoptosis and nitric oxide production. Notably, indomethacin did not affect inflammation parameters in the kidneys (e.g. MCP-1, ED1+-cells). On the other hand, probenecid blocked indomethacin induced restoration of Oat1/3 and moreov...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research