title: Iodinated contrast media cause direct tubular cell damage, leading to oxidative stress, low nitric oxide, and impairment of tubuloglomerular feedback.
abstract: Iodinated contrast media (CM) have adverse effects that may result in contrast-induced acute kidney injury. Oxidative stress is believed to play a role in CM-induced kidney injury. We test the hypothesis that oxidative stress and reduced nitric oxide in tubules are consequences of CM-induced direct cell damage and that increased local oxidative stress may increase tubuloglomerular feedback. Rat thick ascending limbs (TAL) were isolated and perfused. Superoxide and nitric oxide were quantified using fluorescence techniques. Cell death rate was estimated using propidium iodide and trypan blue. The function of macula densa and tubuloglomerular feedback responsiveness were measured in isolated, perfused juxtaglomerular apparatuses (JGA) of rabbits. The expression of genes related to oxidative stress and the activity of superoxide dismutase (SOD) were investigated in the renal medulla of rats that received CM. CM increased superoxide concentration and reduced nitric oxide bioavailability in TAL. Propidium iodide fluorescence and trypan blue uptake increased more in CM-perfused TAL than in controls, indicating increased rate of cell death. There were no marked acute changes in the expression of genes related to oxidative stress in medullary segments of Henle's loop. SOD activity did not differ between CM and control groups. The tubuloglomerular feedback in isolated JGA was increased by CM. Tubular cell damage and accompanying oxidative stress in our model are consequences of CM-induced direct cell damage, which also modifies the tubulovascular interaction at the macula densa, and may therefore contribute to disturbances of renal perfusion and filtration.
authors.affiliation: Institut für Vegetative Physiologie, Charité, Universitätsmedizin Berlin, Berlin, Germany. andreas.patzak@charite.de.
authors.forename: Zhi Zhao
authors.initials: ZZ
authors.lastname: Liu
authors.forename: Kristin
authors.initials: K
authors.lastname: Schmerbach
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lu
authors.forename: Andrea
authors.initials: A
authors.lastname: Perlewitz
authors.forename: Tatiana
authors.initials: T
authors.lastname: Nikitina
authors.forename: Kathleen
authors.initials: K
authors.lastname: Cantow
authors.forename: Erdmann
authors.initials: E
authors.lastname: Seeliger
authors.forename: Pontus B
authors.initials: PB
authors.lastname: Persson
authors.forename: Andreas
authors.initials: A
authors.lastname: Patzak
authors.forename: Ruisheng
authors.initials: R
authors.lastname: Liu
authors.forename: Mauricio M
authors.initials: MM
authors.lastname: Sendeski
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000503:physiopathology; D000818:Animals; D001682:Biological Availability; D016923:Cell Death / Q000187:drug effects; D003287:Contrast Media / Q000009:adverse effects*; D025461:Feedback, Physiological / Q000187:drug effects; D066298:In Vitro Techniques; D007606:Juxtaglomerular Apparatus / Q000187:drug effects* / Q000502:physiology; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D008138:Loop of Henle / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism / Q000493:pharmacokinetics; D018384:Oxidative Stress / Q000187:drug effects; D010477:Perfusion; D011817:Rabbits; D051381:Rats; D013481:Superoxides / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects; D014283:Triiodobenzoic Acids / Q000009:adverse effects*
chemical_list: D003287:Contrast Media; D014283:Triiodobenzoic Acids; D013481:Superoxides; D009569:Nitric Oxide; C044834:iodixanol
keywords: acute kidney injury; cell damage; iodinated contrast media; thick ascending limb; tubuloglomerular feedback