Oxidative Cell Membrane Injury
Oxidative Cell Membrane Injury
Majid Ali, M.D.
A cell looks at the world around it through its plasma membrane. A human frame is but a zillion plasma membranes at the surface of and within the confines of cells aligned in an infinite variety of kaleidoscopic mosaics. Health preservation for man, then, is the preservation of the integrity of a zillion cell membranes. Lipid peroxidation is the principle threat to the health of a cell membrane.
The concept of oxidative cell membrane injury by lipid peroxidation is essential to understanding of the initial events in cell injury under both physiologic and pathologic conditions, physiologic aging process, repair or cell loss through cell death, and pathogenesis of disease.
Health preservation or disease, then, can be looked at as the sum total of the process which either preserve the integrity of the cellular milieu or result in irreversible cellular damage resulting in cell death, and when enough cells are damaged or have died, in disease.
All essential life processes involving the integrity of cell plasma membranes are initiated at the cell membrane. The integrity of the plasma cell membrane is essential to the cellular health preservation. Except for genetic disorders, all threats to the integrity of the internal cellular milieu are first posed at the cell membrane. For cellular health, a cell needs to maintain its interface with the world around it within fairly close physical, electromagnetic and biochemical limits. Specifically, the optimal fluidity of the cell membrane is critical to the functional integrity of the cell.
Mechanisms of Cell Membrane Lipid Peroxidation
Since cell membrane is the interface between the cell and its environments, it follows that the cell membrane damage can be expected to result from all forms of threats to the cell health. These include:
1. Geomagnetic disturbances
2. Radiation of different types
3. Ozone, hyperoxia, and nitrogen oxide
4. Chemically-induced changes in the cell membrane oxidant-antioxidant regulatory mechanisms.
5. Cell membrane injury initiated by microorganisms
6. Cell membrane changes initiated by mechanical trauma
The major pathogenetic mechanisms involved in the cell membrane lipid peroxidation include the following: production of free radicals, oxidative structural damage to the polyunsaturated fatty acids of the cell membrane, inactivation of the complimentary systems, and triggering of antibody-antigen complex information.
Radical Chain Reactions in Membrane Peroxidation
The essential initial event in oxidative damage to the polyunsaturated fatty acids is the abstraction of hydrogen from the unsaturated fatty acid:
LH-– —> L.
The lipid radical (l.) so formed is now available to react with molecular oxygen in the environment of the cell membrane:
L. + O2 —> LOO.
The above initial events trigger radical chain reactions:
LOO. + L’H —> LOOH + L.’
The products formed by the above reactions are monohydroperoxide (LOOH). These molecules in the presence of metal catalyst initiate further radical chain reactions:
LOOH + Fe2+ —> LO. + Fe3 + HO–
LOOH + Fe3+ —> LOO. + Fe2+ + H+
The products formed by the above reaction are called lipid alkoxy radical (LO.). These radicals undergo cleavage of C-C bonds. Such cleavage leads to formation of unsaturated fatty acid aldehydes and alkyl radicals. These radicals, in turn, trigger additional chain reactions. The omega 3 unsaturated fatty acid yield ethane, and the omega 6 fatty acids yield N-pentane. Metal ions are essential for this lipid hydroperoxide degradation. A number of other reaction products are also formed during spontaneous or thermal decomposition of monohydroperoxides. One of the products formed by lipid peroxidation is malondialdehyde which is the main reaction product measurable in biologic systems.