PMID- 18468994
OWN - NLM
STAT- MEDLINE
DCOM- 20090130
LR  - 20220311
IS  - 1522-9645 (Electronic)
IS  - 0195-668X (Linking)
VI  - 29
IP  - 20
DP  - 2008 Oct
TI  - Contrast agents and renal cell apoptosis.
PG  - 2569-76
LID - 10.1093/eurheartj/ehn197 [doi]
AB  - AIMS: Contrast media (CM) induce a direct toxic effect on renal tubular cells. 
      This toxic effect may have a role in the pathophysiology of contrast nephropathy. 
      METHODS AND RESULTS: We evaluated (i) the cytotoxicity of CM [both low-osmolality 
      (LOCM) and iso-osmolality (IOCM)], of iodine alone, and of an hyperosmolar 
      solution (mannitol 8%) on human embryonic kidney (HEK 293), porcine proximal 
      renal tubular (LLC-PK1), and canine Madin-Darby distal tubular renal (MDCK) 
      cells; and (ii) the effectiveness of various antioxidant compounds 
      [n-acetylcysteine (NAC), ascorbic acid and sodium bicarbonate] in preventing CM 
      cytotoxicity. The cytotoxicity of CM was assessed at different time points, with 
      different methods: cell viability, DNA laddering, flow cytometry, and caspase 
      activation. Both LOCM and IOCM produced a concentration- and time-dependent 
      increase in cell death as assessed by the different methods. On the contrary, 
      iodine alone and hyperosmolar solution did not induce any significant cytotoxic 
      effect. There was not any significant difference in the cytotoxic effect between 
      LOCM and IOCM. Furthermore, both LOCM and IOCM caused a marked increase in 
      caspase-3 and -9 activities and poly(ADP-ribose) fragmentation, while no effect 
      on caspase-8/-10 was observed, thus indicating that the CM activated apoptosis 
      mainly through the intrinsic pathway. Both CM induced an increase in protein 
      expression levels of pro-apoptotic members of the Bcl2 family (Bim and Bad). NAC 
      and ascorbic acid but not sodium bicarbonate had a dose-dependent protective 
      effect on renal cells after 3 h incubation with high dose (200 mg iodine/mL) of 
      both LOCM and IOCM. CONCLUSION: Both LOCM and IOCM induce a dose-dependent renal 
      cell apoptosis. NAC and ascorbic acid but not sodium bicarbonate prevent this 
      contrast-induced apoptosis.
FAU - Romano, Giulia
AU  - Romano G
AD  - Department of Cellular and Molecular Biology and Pathology, Federico II 
      University of Naples, Naples, Italy.
FAU - Briguori, Carlo
AU  - Briguori C
FAU - Quintavalle, Cristina
AU  - Quintavalle C
FAU - Zanca, Ciro
AU  - Zanca C
FAU - Rivera, Natalia V
AU  - Rivera NV
FAU - Colombo, Antonio
AU  - Colombo A
FAU - Condorelli, Gerolama
AU  - Condorelli G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080508
PL  - England
TA  - Eur Heart J
JT  - European heart journal
JID - 8006263
RN  - 0 (Contrast Media)
RN  - 0 (Triiodobenzoic Acids)
RN  - 182ECH14UH (iobitridol)
RN  - 4419T9MX03 (Iohexol)
RN  - EC 3.4.22.- (Caspases)
RN  - HW8W27HTXX (iodixanol)
RN  - PQ6CK8PD0R (Ascorbic Acid)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Ascorbic Acid/administration & dosage
MH  - Caspases/drug effects/metabolism
MH  - Cell Death/drug effects
MH  - Cell Line
MH  - Contrast Media/*adverse effects
MH  - Dogs
MH  - Epithelial Cells/metabolism
MH  - Flow Cytometry
MH  - Humans
MH  - Iohexol/adverse effects/*analogs & derivatives
MH  - Kidney Tubules/*drug effects/metabolism
MH  - Osmolar Concentration
MH  - Swine
MH  - Triiodobenzoic Acids/*adverse effects
EDAT- 2008/05/13 09:00
MHDA- 2009/01/31 09:00
CRDT- 2008/05/13 09:00
PHST- 2008/05/13 09:00 [pubmed]
PHST- 2009/01/31 09:00 [medline]
PHST- 2008/05/13 09:00 [entrez]
AID - ehn197 [pii]
AID - 10.1093/eurheartj/ehn197 [doi]
PST - ppublish
SO  - Eur Heart J. 2008 Oct;29(20):2569-76. doi: 10.1093/eurheartj/ehn197. Epub 2008 
      May 8.