Document Detail


Reactive oxygen species independent cytotoxicity induced by radiocontrast agents in tubular cells (LLC-PK1 and MDCK).
MedLine Citation:
PMID:  17365925     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Radiocontrast agents (RAs) cause renal tubular damage by hemodynamic imbalance, which could cause hypoxic stimulus and direct cytotoxicity. However, reactive oxygen species (ROS) could be an important factor in RAs' direct cytotoxicity. This study investigated the involvement of ROS in deleterious effects produced by RAs on normoxic and hypoxic renal tubular cells. MATERIALS AND METHODS: LLC-PK1 and MDCK were exposed to diatrizoate and ioxaglate in normoxic and hypoxic conditions. Apoptotic and necrotic cell death were assessed by acridine orange/ethidium bromide and annexin V methods. Hydrogen peroxide, superoxide anion, and malondialdehyde levels were analyzed by, respectively, 2',7'-dichlorofluorescein, luminal, and thiobarbituric acid. Antioxidant agents were used to prevent cellular RAs damage. RESULTS: Diatrizoate and ioxaglate decreased cellular viability in both cells, and this effect was enhanced by hypoxic conditions. Diatrizoate induced more injury than ioxaglate to both cell lines. LLC-PK1 underwent necrosis, while MDCK cells underwent apoptosis when exposed to diatrizoate. These results could not be attributed to an increase in osmolality. RAs did not increase hydrogen peroxide, superoxide anion or malondialdehyde levels in both cells. Additionally, N-acetyl-L-cysteine (NAC), ascorbic acid, alpha-tocopherol, glutathione, beta-carotene, allopurinol, cimetidine, and citric acid did not protect cells against RAs damage. Surprising, NAC increased the cellular damage induced by ioxaglate in the both cell lines. CONCLUSION: The present study shows that RAs induce damage in cultured tubular cells, especially in hypoxic conditions. ROS were not involved in the observed RAs' cytotoxicity, and NAC increased ioxaglate-induced tubular damage.
Authors:
Andrezza Sanches Garofalo; Fernanda Teixeira Borges; Maria Aparecida Dalboni; Oscar Fernando Pavão dos Santos
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Renal failure     Volume:  29     ISSN:  0886-022X     ISO Abbreviation:  Ren Fail     Publication Date:  2007  
Date Detail:
Created Date:  2007-03-16     Completed Date:  2007-05-14     Revised Date:  2008-05-21    
Medline Journal Info:
Nlm Unique ID:  8701128     Medline TA:  Ren Fail     Country:  United States    
Other Details:
Languages:  eng     Pagination:  121-31     Citation Subset:  IM    
Affiliation:
Nephrology Division, Medicine Department, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
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MeSH Terms
Descriptor/Qualifier:
Acetylcysteine / pharmacology
Animals
Antioxidants / pharmacology
Cell Hypoxia
Cell Line
Cell Line, Tumor
Cell Survival / drug effects*,  radiation effects
Contrast Media
Dogs
Kidney
L-Lactate Dehydrogenase / analysis
Lung Neoplasms
Necrosis
Radioisotopes / pharmacology
Reactive Oxygen Species / metabolism*
Swine
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Contrast Media; 0/Radioisotopes; 0/Reactive Oxygen Species; 616-91-1/Acetylcysteine; EC 1.1.1.27/L-Lactate Dehydrogenase

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