Document Detail

Oxygen radical-mediated pulmonary toxicity induced by some cationic liposomes.
MedLine Citation:
PMID:  10888302     Owner:  NLM     Status:  MEDLINE    
PURPOSE: The objectives of this study are to investigate the toxicity associated with polycationic liposomes and to elucidate the underlying mechanism. We tested the hypothesis that the positive charge of liposomes is a key determinant of toxicity by testing differently charged liposomes in mice. METHODS: Differently charged liposomal systems including cationic liposomes, LipofectAMINE and DOTAP, and neutral and negative liposomes were evaluated for their toxicity after pulmonary administration in mice. LDH assay and differential cell counts were performed to measure toxicity and pulmonary inflammation, respectively. Reactive oxygen intermediates (ROI) were assessed by chemiluminescence. RESULTS: Instillation of cationic liposomes elicited dose-dependent toxicity and pulmonary inflammation. This effect was more pronounced with the multivalent cationic liposome LipofectAMINE as compared to the monovalent cationic DOTAP. Neutral and negative liposomes did not exhibit lung toxicity. Toxicity associated with cationic liposomes correlated with the oxidative burst induced by the liposomes. LipofectAMINE induced a dose-dependent increase in ROI generation. This effect was less pronounced with DOTAP and absent with neutral and negative liposomes. CONCLUSIONS: ROI play a key role in cationic lipid-mediated toxicity. Polyvalent cationic liposomes cause a release of ROI which are responsible for the pulmonary toxicity.
S Dokka; D Toledo; X Shi; V Castranova; Y Rojanasakul
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Pharmaceutical research     Volume:  17     ISSN:  0724-8741     ISO Abbreviation:  Pharm. Res.     Publication Date:  2000 May 
Date Detail:
Created Date:  2000-12-05     Completed Date:  2000-12-05     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  521-5     Citation Subset:  IM    
West Virginia University, Department of Basic Pharmaceutical Sciences, Morgantown 26506, USA.
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MeSH Terms
Bronchoalveolar Lavage Fluid / cytology
Chemiluminescent Measurements
Cyclic N-Oxides
Free Radical Scavengers / pharmacology
L-Lactate Dehydrogenase / metabolism
Liposomes / toxicity*
Lung Diseases / chemically induced*,  enzymology,  pathology
Mice, Inbred BALB C
Nitrogen Oxides / pharmacology
Reactive Oxygen Species / metabolism*
Grant Support
Reg. No./Substance:
0/Cations; 0/Cyclic N-Oxides; 0/Free Radical Scavengers; 0/Liposomes; 0/Nitrogen Oxides; 0/Reactive Oxygen Species; 3376-24-7/phenyl-N-tert-butylnitrone; EC Dehydrogenase

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