Faculty Collaboration Database

Nitric oxide inhibition of free radical-mediated lipid peroxidation in photodynamically treated membranes and cells. Free Radic Biol Med 2003 Apr 15;34(8):997-1005

Date

04/10/2003

Pubmed ID

12684084

DOI

10.1016/s0891-5849(03)00026-1

Scopus ID

2-s2.0-0037446374 (requires institutional sign-in at Scopus site)   40 Citations

Abstract

Of the numerous biological activities attributed to nitric oxide ((*)NO), relatively little is known about its ability to intercept lipid-derived free radicals and thus protect cells against the damaging effects of lipid peroxidation, particularly in photodynamic settings. To address this, we asked how the (*)NO donor spermine-NONOate (SPER/NO) would affect porphyrin (PpIX)-photosensitized, iron/ascorbate-amplified chain peroxidation in cholesterol (Ch)/phospholipid (0.8:1.0, mol/mol) liposomes. Several Ch oxidation products (ChOX) were monitored by high performance chromatographic techniques. When added immediately before irradiation, SPER/NO (0.4 mM) had no effect on accumulation of 5alpha-hydroperoxide, a primary singlet oxygen-derived ChOX, but strongly suppressed the secondary species arising from postphotooxidation chain reactions, including 7alpha/7beta-hydroperoxides, 7alpha/7beta-hydroxides, and 5,6-epoxides. Metabolism of exogenous 5-aminolevulinate to PpIX in COH-BR1 tumor cells sensitized them to ChOX photogeneration and necrotic photokilling. When present during irradiation, active (but not decomposed) SPER/NO strongly inhibited both effects. These findings support the hypothesis that suitably presented NO, by intercepting lipid-derived radicals, can antagonize the antitumor effects of photodynamic therapy and other oxidative therapies.

Author List

Niziolek M, Korytowski W, Girotti AW

Author

Albert W. Girotti PhD Adjunct Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cell Line, Tumor
Cell Membrane
Chromatography, High Pressure Liquid
Dose-Response Relationship, Radiation
Free Radicals
Humans
Light
Lipid Peroxidation
Liposomes
Models, Chemical
Necrosis
Nitric Oxide
Oxygen
Photochemotherapy
Porphyrins