Chlorophyllin as a protector of mitochondrial membranes against gamma-radiation and photosensitization

Toxicology. 2000 Nov 30;155(1-3):63-71. doi: 10.1016/s0300-483x(00)00278-x.

Abstract

Ionizing radiation and photosensitization are highly damaging events and they generate oxygen-derived free radicals as well as excited species. However, the types as well as extent of reactive oxygen species (ROS) differ. They have been linked to various pathological conditions. Hence natural compounds capable of preventing oxidative damage induced by these agents may have potential applications. Chlorophyllin (CHL), the water-soluble analogue of chlorophyll, has been examined for its ability to inhibit membrane damage induced by y-radiation and photosensitization involving methylene blue plus visible light. Using rat liver mitochondria as model systems the mechanisms of damage induced by these two agents as well as its possible prevention by CHL have been examined. The parameters used were lipid peroxidation as assessed by formation of thiobarbituric acid reactive substances (TBARS) and 4-hydroxynonenal (4-HNE), protein oxidation besides glutathione (GSH) and superoxide dismutase (SOD). Peroxidation increases with radiation dose, in the range of 75-600 Gy. A similar observation also was observed with photosensitization, as a function of time. CHL, at a concentration of 10 microM offered a high degree of protection against radiation and photosensitization as indicated by decreased peroxidation, protein oxidation as well as the restoration of GSH and SOD. When compared with the established antioxidants, ascorbic acid and GSH, CHL offered a much higher degree of protection. Pulse radiolysis studies show that this compound has a relatively high rate constant with hydroxyl radical (*OH), a crucial species generated during y-radiation. Hence the studies show that CHL is a potent antioxidant in mitochondrial membranes.

MeSH terms

  • Aldehydes / metabolism
  • Animals
  • Antioxidants / pharmacology
  • Ascorbic Acid / pharmacology
  • Chlorophyllides / pharmacology*
  • Chromatography, High Pressure Liquid
  • Dose-Response Relationship, Drug
  • Female
  • Free Radical Scavengers / pharmacology
  • Gamma Rays
  • Glutathione / metabolism
  • Glutathione / pharmacology
  • In Vitro Techniques
  • Intracellular Membranes / drug effects*
  • Intracellular Membranes / radiation effects
  • Light
  • Lipid Peroxidation / drug effects
  • Lipid Peroxidation / radiation effects
  • Methylene Blue / pharmacology
  • Mitochondria, Liver / drug effects*
  • Mitochondria, Liver / radiation effects
  • Oxidation-Reduction
  • Photosensitizing Agents / pharmacology
  • Proteins / metabolism
  • Pulse Radiolysis
  • Radiation-Protective Agents / pharmacology*
  • Rats
  • Rats, Wistar
  • Superoxide Dismutase / metabolism
  • Thiobarbituric Acid Reactive Substances / metabolism

Substances

  • Aldehydes
  • Antioxidants
  • Chlorophyllides
  • Free Radical Scavengers
  • Photosensitizing Agents
  • Proteins
  • Radiation-Protective Agents
  • Thiobarbituric Acid Reactive Substances
  • Superoxide Dismutase
  • chlorophyllin
  • Glutathione
  • 4-hydroxy-2-nonenal
  • Ascorbic Acid
  • Methylene Blue