These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Low-dose indomethacin after ischemic acute kidney injury prevents downregulation of Oat1/3 and improves renal outcome.
    Author: Schneider R, Meusel M, Renker S, Bauer C, Holzinger H, Roeder M, Wanner C, Gekle M, Sauvant C.
    Journal: Am J Physiol Renal Physiol; 2009 Dec; 297(6):F1614-21. PubMed ID: 19794109.
    Abstract:
    We have previously shown that expression of renal organic anion transporters Oat1 and Oat3 is diminished by prostaglandin E(2) (PGE(2)) and that both transporters are downregulated after renal ischemia. Because PGE(2) is increased after renal ischemia and is generated by cyclooxygenases (COX), we investigated the effect of the COX inhibitor indomethacin on expression of Oat1/3 after ischemic acute kidney injury (iAKI). iAKI was induced in rats by bilateral clamping of renal arteries for 45 min. Indomethacin (1 mg/kg) was given intraperitoneally as soon as reperfusion started. Sham-treated animals served as controls. Oat1/3 were determined by qPCR and Western blot. PGE(2) in blood and urine was measured by enzyme-linked immunosorbent assay. Invasion of monocytes/macrophages was determined. Glomerular filtration rate and renal plasma flow were determined. All parameters were detected 24 h after ischemia. PAH net secretion, as well as clearance and secretion of PGE(2) were calculated. In clamped animals, indomethacin restored expression of Oat1/3, as well as PAH net secretion, PGE(2) clearance, or PGE(2) secretion. Additionally, indomethacin substantially improved kidney function as measured by glomerular filtration and PAH clearance. Indomethacin did not affect ischemia-induced invasion of monocytes/macrophages. In conclusion, our study indicates that low-dose indomethacin applied after ischemia prevents ischemia-induced downregulation of Oat1/3 during reperfusion and has a substantial protective effect on kidney function after iAKI. The beneficial effect of low-dose indomethacin on renal outcome is likely due to an effect different from inhibition of inflammation. In accordance to the decreased PAH net secretion, renal excretion of an endogenous organic anion (PGE(2)) is also impaired after ischemia and reperfusion.
    [Abstract] [Full Text] [Related] [New Search]