Oxygen Radical-Mediated Pulmonary Toxicity Induced by Some Cationic Liposomes

Details

• Personal Author:
  Castranova, Vincent ; Dokka S ; Rojanasakul Y ; Shi X ; Toledo D
• Description:
  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. 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. 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. 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. [Description provided by NIOSH]
• Subjects:
  Animals Hazardous Substances Laboratories Lung Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Animal Studies Author Keywords: Cationic Liposomes Charge Laboratory Animals Lung Disorders Pulmonary System Disorders Reactive Oxygen Intermediates Respiratory System Disorders Toxicity Toxins
• ISSN:
  0724-8741
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Pennsylvania ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  17
• Issue:
  5
• NIOSHTIC Number:
  nn:20020655
• Citation:
  Pharm Res 2000 May; 17(5):521-525
• Email:
  yrojanasakul@hsc.wvu.edu
• Federal Fiscal Year:
  2000
• Peer Reviewed:
  True
• Source Full Name:
  Pharmaceutical Research
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:020c8fe0460b8816b6e17631b0c387b8c2e095aafc31b8b6c142a72f6e3bad0e8bba8af119fcfd8608f94b358e277897cabf5612cd7b7b6e82c9b349a4fa4ecf
• Download URL:
  https://stacks.cdc.gov/view/cdc/198339/cdc_198339_DS1.pdf
• File Type:
  [PDF - 193.06 KB ]