Comparison of iohexol and iodixanol induced nephrotoxicity, mitochondrial damage and mitophagy in a new contrast-induced acute kidney injury rat model

Comparison of iohexol and iodixanol induced nephrotoxicity, mitochondrial damage and mitophagy in... Recent progress in angiography and interventional therapy has revived interest in comparison of nephrotoxicity of low-or iso-osmolar contrast media, but detailed mechanisms and effective treatments of contrast-induced acute kidney injury (CI-AKI) remain elusive. We established a new model of CI-AKI and compared the nephrotoxicity of iohexol and iodixanol with a focus on renal oxidative stress, mitochondrial damage and mitophagy. Our results showed that 48-h dehydration plus furosemide injection before iohexol administration successfully induced CI-AKI in rats. Compared with iodixanol, iohexol induced a greater decrease in renal function, more severe morphological damage and mitochondrial ultrastructural changes, an increased number of apoptotic cells, decreased antioxidative enzymes with activation of NLRP3 inflammasome in renal tissue. Renal contrast media kinetics showed the immediate excretion of iohexol and the transient renal accumulation of iodixanol. Plasma mtDNA Tc numbers were positively correlated with markers of renal mitochondrial disruption but negatively correlated with the level of serum creatinine and the score of tubular injury. Of note, iodixanol appeared to induce a stronger activation of mitophagy than iohexol, evidenced by greater protein levels of LC3II and PINK1/Parkin in the renal tissue of iodixanol-treated rats. Taken together, our results indicate that iohexol induced more severe nephrotoxicity than iodixanol in vivo due to apoptosis, destruction of antioxidative defense machinery, activation of NLRP3 inflammasome, mitochondrial damage and mitophagy. Plasma mtDNA may serve as a biological marker for renal mitochondrial disruption and damage in CI-AKI. Antioxidative defense and mitophagy are involved in the process of CI-AKI and may be promising targets of therapies. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Toxicology Springer Journals

Comparison of iohexol and iodixanol induced nephrotoxicity, mitochondrial damage and mitophagy in a new contrast-induced acute kidney injury rat model

Download PDF
13 pages
Read Article

Loading next page...
 
/lp/springer_journal/comparison-of-iohexol-and-iodixanol-induced-nephrotoxicity-3bToVEewjC
Publisher
Springer Journals
Copyright
Copyright © 2018 by Springer-Verlag GmbH Germany, part of Springer Nature
Subject
Biomedicine; Pharmacology/Toxicology; Occupational Medicine/Industrial Medicine; Environmental Health; Biomedicine, general
ISSN
0340-5761
eISSN
1432-0738
DOI
10.1007/s00204-018-2225-9
Publisher site
See Article on Publisher Site

Abstract

Recent progress in angiography and interventional therapy has revived interest in comparison of nephrotoxicity of low-or iso-osmolar contrast media, but detailed mechanisms and effective treatments of contrast-induced acute kidney injury (CI-AKI) remain elusive. We established a new model of CI-AKI and compared the nephrotoxicity of iohexol and iodixanol with a focus on renal oxidative stress, mitochondrial damage and mitophagy. Our results showed that 48-h dehydration plus furosemide injection before iohexol administration successfully induced CI-AKI in rats. Compared with iodixanol, iohexol induced a greater decrease in renal function, more severe morphological damage and mitochondrial ultrastructural changes, an increased number of apoptotic cells, decreased antioxidative enzymes with activation of NLRP3 inflammasome in renal tissue. Renal contrast media kinetics showed the immediate excretion of iohexol and the transient renal accumulation of iodixanol. Plasma mtDNA Tc numbers were positively correlated with markers of renal mitochondrial disruption but negatively correlated with the level of serum creatinine and the score of tubular injury. Of note, iodixanol appeared to induce a stronger activation of mitophagy than iohexol, evidenced by greater protein levels of LC3II and PINK1/Parkin in the renal tissue of iodixanol-treated rats. Taken together, our results indicate that iohexol induced more severe nephrotoxicity than iodixanol in vivo due to apoptosis, destruction of antioxidative defense machinery, activation of NLRP3 inflammasome, mitochondrial damage and mitophagy. Plasma mtDNA may serve as a biological marker for renal mitochondrial disruption and damage in CI-AKI. Antioxidative defense and mitophagy are involved in the process of CI-AKI and may be promising targets of therapies.

Journal

Archives of Toxicology – Springer Journals

Published: Jun 2, 2018

References

  • Nephrotoxicity of contrast media and protective effects of acetylcysteine
    Briguori, C; Quintavalle, C; Micco, F; Condorelli, G
  • A comparison between two different definitions of contrast-induced acute kidney injury in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention
    Centola, M; Lucreziotti, S; Salerno-Uriarte, D
  • Contrast enhancement pharmacokinetics of six ionic and nonionic contrast media
    Dean, PB; Kivisaari, L; Kormano, M
  • Nephrotoxicity of high- and low-osmolar contrast media. The protective role of amlodipine in a rat model
    Duan, SB; Liu, FY; Luo, JA
  • Comparative cytotoxicity of high-osmolar and low-osmolar contrast media on HKCs in vitro
    Duan, S; Zhou, X; Liu, F
  • PINK1/Parkin-mediated mitophagy in mammalian cells
    Eiyama, A; Okamoto, K
  • Mitochondrial dysfunction in inherited renal disease and acute kidney injury
    Emma, F; Montini, G; Parikh, SM; Salviati, L
  • In vivo multiphoton imaging of mitochondrial structure and function during acute kidney injury
    Hall, AM; Rhodes, GJ; Sandoval, RM; Corridon, PR; Molitoris, BA
  • Preclinical pharmacokinetics and general toxicology of iodixanol
    Heglund, IF; Michelet, AA; Blazak, WF; Furuhama, K; Holtz, E
  • Urinary mitochondrial DNA levels identify acute kidney injury in surgical critical illness patients
    Hu, Q; Ren, J; Wu, J
  • Autophagy in acute kidney injury
    Kaushal, GP; Shah, SV
  • Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)
    Kellum, JA; Lameire, N; Group, KAGW
  • A human serum albumin-thioredoxin fusion protein prevents experimental contrast-induced nephropathy
    Kodama, A; Watanabe, H; Tanaka, R
  • Mitophagy plays a protective role in iodinated contrast-induced acute renal tubular epithelial cells injury
    Lei, R; Zhao, F; Tang, C-Y
  • The RIP1-kinase inhibitor necrostatin-1 prevents osmotic nephrosis and contrast-induced AKI in mice
    Linkermann, A; Heller, JO; Prokai, A
  • A novel contrast-induced acute kidney injury model based on the 5/6-nephrectomy rat and nephrotoxicological evaluation of iohexol and iodixanol in vivo
    Liu, TQ; Luo, WL; Tan, X
  • A new scoring model for the prediction of mortality in patients with acute kidney injury
    Luo, M; Yang, Y; Xu, J
  • Glutathione and mitochondria determine acute defense responses and adaptive processes in cadmium-induced oxidative stress and toxicity of the kidney
    Nair, AR; Lee, WK; Smeets, K
  • Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome
    Nakahira, K; Haspel, JA; Rathinam, VA
  • Protective effect of the grape seed proanthocyanidin extract in a rat model of contrast-induced nephropathy
    Ozkan, G; Ulusoy, S; Orem, A
  • Nephrotoxic tubular and interstitial lesions: morphology and classification
    Racusen, LC; Solez, K
  • The relative renal safety of iodixanol compared with low-osmolar contrast media: a meta-analysis of randomized controlled trials
    Reed, M; Meier, P; Tamhane, UU; Welch, KB; Moscucci, M; Gurm, HS
  • NLRP3 inflammasome mediates contrast media-induced acute kidney injury by regulating cell apoptosis
    Shen, J; Wang, L; Jiang, N
  • Risk prediction models for contrast induced nephropathy: systematic review
    Silver, SA; Shah, PM; Chertow, GM; Harel, S; Wald, R; Harel, Z
  • Elevated levels of plasma mitochondrial DNA DAMPs are linked to clinical outcome in severely injured human subjects
    Simmons, JD; Lee, YL; Mulekar, S
  • A novel rat model of contrast-induced acute kidney injury
    Sun, S; Zhang, T; Nie, P
  • High mobility group box 1 (HMGB1) activates an autophagic response to oxidative stress
    Tang, D; Kang, R; Livesey, KM; Zeh, HJ; Lotze, MT
  • Mitophagy: basic mechanism and potential role in kidney diseases
    Tang, C; He, L; Liu, J; Dong, Z
  • PINK1-PRKN/PARK2 pathway of mitophagy is activated to protect against renal ischemia-reperfusion injury
    Tang, C; Han, H; Yan, M
  • Contrast media and the kidney: European Society of Urogenital Radiology (ESUR) guidelines
    Thomsen, HS; Morcos, SK
  • Role of mitochondrial DNA in septic AKI via toll-Like receptor 9
    Tsuji, N; Tsuji, T; Ohashi, N; Kato, A; Fujigaki, Y; Yasuda, H
  • Extrusion of mitochondrial contents from lipopolysaccharide-stimulated cells: involvement of autophagy
    Unuma, K; Aki, T; Funakoshi, T; Hashimoto, K; Uemura, K
  • Periprocedural effects of statins on the incidence of contrast-induced acute kidney injury: a systematic review and trial sequential analysis
    Wang, N; Qian, P; Yan, TD; Phan, K
  • Urinary mitochondrial DNA is a biomarker of mitochondrial disruption and renal dysfunction in acute kidney injury
    Whitaker, RM; Stallons, LJ; Kneff, JE
  • The mitochondria-targeted antioxidant MitoQ ameliorated tubular injury mediated by mitophagy in diabetic kidney disease via Nrf2/PINK1
    Xiao, L; Xu, X; Zhang, F
  • Preventive effect of pentoxifylline on contrast-induced acute kidney injury in hypercholesterolemic rats
    Yang, SK; Duan, SB; Pan, P; Xu, XQ; Liu, N; Xu, J
  • HPLC method validation for the quantification of lomustine to study pharmacokinetics of thermosensitive liposome-encapsulated lomustine containing iohexol for CT imaging in C6 glioma rats
    Zhuang, L; Gao, J; Zeng, Y

You’re reading a free preview. Subscribe to read the entire article.

Try 2 weeks free now

DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

or browse the journals available

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off

Sign up
for free
Start 14 day
Free Trial