Antioxidant Depletion, Lipid Peroxidation, and Impairment of Calcium Transport Induced by Air-Blast Overpressure in Rat Lungs

Abstract

Exposure to blast overpressure, or the sudden rise in atmospheric pressure after explosive detonation, results in damage mainly of the gas-filled organs. In addition to the physical damage, in the lung, injury may proceed via a hemorrhage-dependent mechanism initiating oxidative stress and accumulation of lipid peroxidation products. Massive rupture of capillaries and red blood cells, release of hemoglobin, its oxidation to met-hemoglobin and degradation sets the stage for heme-catalyzed oxidations. The authors hypothesized that lipid hydroperoxides interact with met-hemoglobin in the lungs of exposed animals to produce ferryl-hemoglobin, an extremely potent oxidant that induces oxidative damage by depleting antioxidants and initiating peroxidation reactions. Oxidation-induced disturbance of Ca²⁺ homeostasis facilitates further amplification of the damage. To test this hypothesis, groups of anesthetized rats (6 rats/group) were exposed to blast at 3 peak pressures: low (61.2 kPa), medium (95.2 kPa), high (136 kPa). One group served as an unexposed control. Immediately after exposure, the rats were euthanized and the lungs were analyzed for biochemical parameters. Blast overpressure caused: (1) depletion of total and water-soluble pulmonary antioxidant reserves and individual antioxidants (ascorbate, vitamin E, GSH), (2) accumulation of lipid peroxidation products (conjugated dienes, TBARS), and (3) inhibition of ATP-dependent Ca²⁺ transport. The magnitude of these changes in the lungs was proportional to the peak blast overpressure. Inhibition of Ca²⁺ transport strongly correlated with both depletion of antioxidants and enhancement of lipid peroxidation. In model experiments, met-hemoglobin/H₂O₂ produced damage to Ca²⁺ transport in the lungs from control animals similar to that observed in the lungs from blast overpressure-exposed animals. Ascorbate, which is known to reduce ferryl-hemoglobin, protected against met-hemoglobin/H₂O₂-induced damage of Ca²⁺ transport. If ferryl-hemoglobin is the major reactive oxygen species released by hemorrhage, then its specific reductants (e.g., nitric oxide) along with other antioxidants may be beneficial protectants against pulmonary barotrauma.

Key Words:

• oxidative stress
• lipid peroxidation
• antioxidants
• vitamin E
• vitamin C
• thiols
• Ca²⁺ transport
• air-blast overpressure
• free radicals