Antioxidants to Supplement or Not to Supplement That Is the Question.

Antioxidants, whether from diet or pharmacological supplementation, gained significant popularity among scientists and lay public in recent years, and was claimed to protect or treat numerous ailments. [...].

Pulmonary biochemical and histological alterations after repeated low-level blast overpressure exposures.

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.

Biochemical changes in mouse lung after subcutaneous injection of the sulfur mustard 2-chloroethyl 4-chlorobutyl sulfide.

Sulfur mustard (HD) is a vesicant-type chemical warfare agent (CWA) introduced in World War I which continues to be produced, stockpiled, and occasionally deployed by some countries, and could be used potentially by terrorists. Exposure to HD can cause erythema, blisters, corneal opacity, and airway damage. We have reported previously that subcutaneous (SC) injection of immunodeficient athymic nude mice with the half mustard butyl 2-chloroethyl sulfide (BCS) causes systemic biochemical changes in several organs distal to the exposure site. In the present study, we examined the response of non-immunodeficient Swiss Webster mice to the mustard, 2-chloroethyl 4-chlorobutyl sulfide (CECBS). In a pilot study, we found that a single SC injection of 20-25 microl/mouse causes death within 24h. Consequently, we used 5 microl/mouse (approx. 0.017 mg/kg body weight) of neat CECBS or an equal volume of saline as control. We examined the lungs after 1, 24, and 48 h for biochemical changes including total and oxidized glutathione, protein, DNA, and lipid peroxidation contents in tissue homogenate, and superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase, and glutathione S-transferases activities in the cytosol. After 1h and/or 24h, we found statistically significant changes that were resolved by 48 h. These changes mimicked those of HD and BCS and were generally consistent with free radical-mediated oxidative stress. The implications of these observations are two-fold. First, dermal exposure to low-dose mustard gas could elicit systemic changes impacting distal organs such as the lungs. It also suggests that antioxidants could potentially modulate the response and reduce the damage. Second, although the use of known CWAs such as HD is prohibited, analogs that are not recognized as agents are as toxic and could be dangerous if acquired and used by potential terrorists.

Interplay between high energy impulse noise (blast) and antioxidants in the lung.

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.

Significant pulmonary response to a brief high-level, nose-only nitrogen dioxide exposure: an interspecies dosimetry perspective.

Brief, high-level nitrogen dioxide (NO(2)) exposures are major hazards during fires and heat-generating explosions. To characterize the lung response to a brief high-level NO(2) exposure, we exposed two groups (n = 5) of 325-375 g, male, Sprague-Dawley rats to either 200 +/- 5 ppm (376 +/- 9 mg/m(3)) NO(2) or room air for 15 min. The rats were nose-only exposed in a multiport exposure chamber fitted with pressure transducers to monitor their respiration during exposure. One hour after exposure, we euthanized the rats, collected blood samples, lavaged the lungs with warm saline, and then excised them. One lung lobe was cooled to -196 degrees C and used for low-temperature electron paramagentic resonance (EPR) analysis. The remainder was homogenized and used for biochemical analyses. Inspired minute ventilation (V(i)) during exposure decreased 59% (p < 0.05). Calculated total inspired dose was 0.880 mg NO(2). In lung lavage, both total and alveolar macrophage cell counts declined (approximately 75%, p < 0.05), but epithelial cell count increased 8.5-fold. Lung weight increased 40% (p < 0.05) after exposure. In the blood, potassium and methemoglobin increased 45 and 18% (p < 0.05), respectively; glucose, lactate, and total hemoglobin were not altered significantly. EPR analysis of lung tissue revealed hemoglobin oxidation and carbon-centered radical formation. Vitamins E and C and uric acid were depleted, and lipid peroxidation measured by three different methods (TBARS, conjugated dienes, and fluorescent peroxidation end products) was elevated, but total protein, DNA, and lipid contents were unchanged. These observations combined demonstrate that a brief (15 min) high-level (200 ppm) NO(2) exposure of rats was sufficient to cause significant damage. However, comparison of the exposure dose normalized to rat body weight with previously reported sheep and estimated human values revealed significant differences. This raises a question about interspecies dosimetry and species-specific responses when animal data are extrapolated to humans and used for safety standard setting, particularly with high-level brief exposures.