ascorbic-acid and Blast-Injuries

High-energy impulse noise (BLAST) is a physical event characterized by an abrupt rise in atmospheric pressure above ambient lasting for a very short period, but potentially causing significant material and biological damage. Exposure to high-level BLAST can be destructive and lethal. Low-level BLAST similar to what is encountered repeatedly by military personnel during training and combat from detonation of munitions and firing of large caliber weapons, and during occupational use of explosives and some heavy machinery, can also cause significant injury. Globally, civilians are increasingly exposed to BLAST resulting from terrorist bombings or abandoned unmarked mines following numerous wars and conflicts. We have shown previously in several animal models that exposure to non-lethal BLAST results in pathological changes, mostly to the hollow organs characterized in the lungs, the most sensitive organ, by rupture of alveolar septa, and pulmonary hemorrhage and edema. These events potentially can cause alveolar flooding, respiratory insufficiency and adult respiratory distress syndrome (ARDS), leading to varying degrees of hypoxia, antioxidant depletion and oxidative damage. We have also observed progressive formation of nitric oxide in blood and other tissues. The totality of these observations supports our general hypothesis that exposure to BLAST can lead to antioxidant depletion and oxidative damage. Understanding the mechanism(s) of BLAST-induced oxidative stress may have important implications that include a potential beneficial role for antioxidants as a prophylaxis or as secondary treatment of injury after exposure alongside other protective and therapeutic modalities. In addition, it suggests a role for endogenous nitric oxide in the injury. This report reviews experimental evidence of BLAST-induced antioxidant depletion, and the potential benefit from antioxidant supplementation before exposure.

Topics: Animals; Antioxidants; Ascorbic Acid; Blast Injuries; Disease Models, Animal; Explosions; Glutathione; Humans; Lung; Lung Injury; Oxidative Stress; Vitamin E

Blast overpressure (BOP), also known as high energy impulse noise, is a damaging outcome of explosive detonations and firing of weapons. Exposure to BOP shock waves alone results in injury predominantly to the hollow organ systems such as auditory, respiratory, and gastrointestinal systems. In recent years, the hazards of BOP that once were confined to military and professional settings have become a global societal problem as terrorist bombings and armed conflicts involving both military and civilian populations increased significantly. We have previously investigated the effects of single BOP exposures at different peak pressures. In this study, we examined the effects of repeated exposure to a low-level BOP and whether the number of exposures or time after exposure would alter the injury outcome. We exposed deeply anesthetized rats to simulated BOP at 62 +/- 2 kPa peak pressure. The lungs were examined immediately after one exposure (1 + 0), or 1 h after one (1 + 1), two (2 + 1), or three (3 + 1) consecutive exposures at 3-min interval. In one group of animals, we examined the effects of repeated exposure on lung weight, methemoglobin, transferrin, antioxidants, and lipid peroxidation. In a second group, the lungs were fixed inflated at 25 cm water, sectioned, and examined histologically after one to three repeated exposures, or after one exposure at 1, 6, and 24 h. We found that single BOP exposure causes notable changes after 1 h, and that repeating BOP exposure did not add markedly to the effect of the first one. However, the effects increased significantly with time from 1 to 24 h. These observations have biological and occupational implications, and emphasize the need for protection from low-level BOP, and for prompt treatment within the first hour following BOP exposure.

Topics: Air Pressure; Animals; Antioxidants; Ascorbic Acid; Blast Injuries; Explosions; Lipid Peroxidation; Lung; Lung Injury; Male; Methemoglobin; Military Personnel; Occupational Diseases; Organ Size; Oxidative Stress; Rats; Rats, Sprague-Dawley; Specific Pathogen-Free Organisms; Time Factors; Transferrin; Vitamin E

Detonation of explosives, firing of large caliber weapons and occupational explosions, professional or accidental, produce high-energy impulse noise (blast) waves characterized by a rapid rise in atmospheric pressure (overpressure) followed by gradual decay to ambient level. Exposure to blast waves causes injury, predominantly to the hollow organs such as ears and lungs. We have previously reported that blast exposure can induce free radical-mediated oxidative stress in the lung characterized by antioxidant depletion, lipid peroxidation, and hemoglobin (Hb) oxidation. In this study, we examined whether pre-loading, adequately fed rats, with pharmacological doses of antioxidants would reduce the response to blast. Sprague-Dawley rats weighing 300-350 g were loaded with either 800 IU vitamin E (VE), 1000 mg vitamin C (VC) or 25 mg lipoic acid (LA) for 3 consecutive days by gavage before exposure to blast. Both VE, and LA were dissolved in 2 ml corn oil, but VC in 2 ml water. After the 3-day antioxidant loading, the rats were divided into six groups (five rats per group), deeply anesthetized with sodium pentobarbital (60 mg/kg body weight), then exposed to a low-level blast (62+/-2 kPa peak pressure and 5 ms duration). A matched number of groups were sham exposed and served as controls. One hour after exposure, all rats were euthanized then blood, and lung tissue was analyzed. We found that antioxidant loading resulted in restored Hb oxygenation, and reduced lipid peroxidation. Lung tissue VE content was elevated after loading but VC did not change possibly due to their different bioavailability and saturation kinetics. These observations, suggest that brief antioxidant loading with pharmacological doses can reduce blast-induced oxidative stress, and may have occupational and clinical implications.

Topics: Animals; Antioxidants; Ascorbic Acid; Blast Injuries; Hemoglobins; Lipid Peroxidation; Lung; Male; Noise; Oxidation-Reduction; Oxidative Stress; Rats; Rats, Sprague-Dawley; Specific Pathogen-Free Organisms; Thioctic Acid; Vitamin E

Exposure to high energy impulse noise (BLAST) caused by explosions, result in structural and functional damage to the hollow organs, especially to the respiratory and auditory systems. Lung damage includes alveolar wall rupture, edema and hemorrhage, and may be fatal. Previous observations at the molecular level using the rat model, suggested that secondary free radical-mediated oxidative stress occurs post exposure resulting in antioxidant depletion and hemoglobin (Hb) oxidation. This study examined whether a short period of pre-exposure supplementation with antioxidants would protect Hb from the effects of BLAST exposure. Six groups of male Sprague-Dawley rats (8/group) were gavaged with 800 IU vitamin E (VE) in 2 ml corn oil, 1000 mg vitamin C (VC) in 2 ml distilled water or 25 mg or (-lipoic acid (LA) in 2 ml corn oil for 3 days. Matched control groups were gavaged with the respective vehicles. On day 4, rats were deeply anesthetized and exposed to a simulated BLAST wave with an average peak pressure of 62 +/- 2 kPa. Rats were euthanized one hour post exposure and blood samples were obtained by cardiac puncture and analyzed using a hemoximeter. Post exposure oxygenation states (HbO2, O2 saturation, and O2 content) were markedly decreased, while reduced-Hb was increased. Supplementation with VE and LA reversed the trend and increased Hb oxygenation, but VC did not. This suggests that a brief dietary loading with pharmacological doses of VE or LA, but not VC shortly before BLAST exposure may be beneficial. Moreover, measurement of blood oxygenation may function as a simple semi-invasive biomarker of BLAST-induced injury applicable to humans.

Topics: Animals; Antioxidants; Ascorbic Acid; Blast Injuries; Hemoglobins; Intubation, Gastrointestinal; Noise; Oxygen; Rats; Rats, Sprague-Dawley; Thioctic Acid; Vitamin E

Blast overpressure (BOP) is a phenomenon that describes the instantaneous rise in atmospheric pressure above ambient, resulting from the firing of large caliber weapons or from military or civilian explosions. Exposure to BOP results in injury to the gas-filled organs, such as the lungs, which exhibit a contusion-type injury. We examined the effects of BOP in rats at 5 and 60 min after exposure to a low-level BOP (62 +/- 3 kPa). The exposure was found to cause oxidative stress in the lung that was characterized by 1) a 3.5-fold decrease in total antioxidant reserves, 2) a depletion of the major water-soluble antioxidants ascorbate and glutathione (GSH) by 50 and 75%, respectively, 3) a depletion of lipid-soluble antioxidant vitamin E by 30%, 4) a 2.5-fold increase of fluorescent end products of lipid peroxidation, and 5) an increased methemoglobin (metHb) content at 60 min after exposure. To elucidate the role of released hemoglobin (Hb) in blast-induced oxidative stress, we studied the interactions of oxyhemoglobin (oxyHb), metHb, and the oxoferryl from of Hb free radical species with two physiologically important reductants, ascorbate and GSH. We found that both ascorbate and GSH were able to convert oxyHb to metHb in a reaction that yielded the one-electron oxidation intermediates semidehydroascorbyl radical and glutathionyl radical, respectively. This reaction did not occur under anaerobic conditions, suggesting that oxyHb-bound O2 acted as the electron acceptor. OxyHb induced peroxidation of cis-parinaric acid in the presence but not absence of ascorbate or GSH. Thus the prooxidant action of water-soluble antioxidants via redox cycling of oxyHb and metHb may promote oxidative stress rather than prevent it.

Topics: Animals; Antioxidants; Ascorbic Acid; Biotransformation; Blast Injuries; Electron Spin Resonance Spectroscopy; Glutathione; Hemoglobins; Lipid Peroxides; Lung; Male; Methemoglobin; Oxidation-Reduction; Oxidative Stress; Oxyhemoglobins; Rats; Rats, Sprague-Dawley; Sulfhydryl Compounds; Vitamin E