Effects of nitrogen dioxide on lactic dehydrogenase isozymes.
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Biomedical subjects
Publications and source records attributed to R D Buckley.
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Comparison of published reports on physiological effects of exposure to ozone (O3) suggests that Canadians are more reactive than southern Californians. Responses of subjects and experimental methods were compared in a cooperative investigation of this apparent difference in reactivity. Four Canadians and four Californians were exposed to 0.37 ppm O3 in purified air at 21 degrees C and 50% relative humidity for 2 hours with intermittent light exercise. Exposures to purified air alone served as controls. Responses of subjects were similar to those observed previously: Canadians on the average showed greater clinical and physiological reactivity to exposure than did Californians, who were no more than minimally reactive. Canadians also showed larger increases in erythrocyte fragility following exposure. No methodological differences sufficient to explain different results of previous studies were found. Although other possible explanations have not been ruled out entirely, adaptation of southern Californians to chronic ambient O3 exposure is a rational hypothesis to explain these results.
Blood from ten young adult male humans, exposed to 1 ppm or 2 ppm nitrogen dioxide (NO2) for 2.5--3.0 hr, was examined for evidence of biochemical changes. The experiments lasted three days. The subjects entered an environmental chamber, performed mild exercise, and completed a series of measurements of pulmonary physiology while breathing filtered air. Blood samples were then taken and analyzed. This regimen was repeated on the second and third day, except that the chamber atmosphere now contained 1 ppm or 2 ppm NO2. Paired group analyses were performed on the data. A statistically significant decrease was observed in the activity of the erythrocyte membrane enzyme acetylcholinesterase at both NO2 levels. Levels of peroxidized red blood cell lipids showed statistically significant elevations after inhalation of 2 ppm NO2 but not 1 ppm. Glucose-6-phosphate dehydrogenase was significantly elevated only after the second 2-ppm NO2 exposure. Small but statistically significant decreases were observed in both hemoglobin and hematocrit values after exposure to both NO2 levels. The experiment was repeated with NO2, (i.e., three days of filtered air) to detect possible effects of the experimental procedure. Decreases were again seen in hemoglobin and hematocrit, and acetyecholinesterase, although of smaller magnitude than when NO2 was inhaled. Other data showed random variations that were not additive over the three-day sham exposure period. It was concluded that significant blood biochemical changes resulted from NO2 inhalation, although the three-day experimental regimen independently produced changes that account for some of the apparent response.
Biochemical studies were performed on blood and lung tissue of squirrel monkeys (Saimiri sciureus) following acute exposure to 0.75 ppm ozone (O3) for 4 h/d for 4 consecutive days. One group of animals was sacrificed at the end of the last exposure day and another group was sacrificed 4 d later after the last exposure. Evidence was sought for oxidation-induced changes known to occur in rodents when high levels of O3 are inhaled. A significant increase in red blood cell membrane fragility was observed, as well as significant decreases in red blood cell glutathione and erythrocyte acetylcholinesterase; however, the red blood cell enzymes, lactic acid dehydrogenase (LDH), and glucose-6-phosphate dehydrogenase (G6PDH) were not changed significantly. Lung tissue analysis showed that lipid peroxidation was markedly increased and tissue vitamin E levels were significantly decreased. The tissue enzymes G6PDH, glutathione reductase, and LDH significantly increased in activity. No significant changes were seen in either superoxide dismutase or malic acid dehydrogenase. The results of this experiment indicate that O3, or reaction products resulting from O3-tissue interaction in the lung, pass the air-blood barrier and are capable of producing biochemical changes in blood as well as in lung tissue.
To determine whether vitamin E (di-alpha-tocopherol) supplementation could protect against short-term respiratory responses to O3 exposure its effects were investigated in young healthy adult volunteers. Experimental groups received 800 or 1600 IU vitamin E per day for 9 or more wk, while control groups received placebo. Subjects were then exposed for 2-h periods to 0.5 ppm O3, with secondary stresses of heat and intermittent light exercise. Responses to O3 exposure, evaluated in terms of symptoms, forced expiratory performance, and single-breath nitrogen washout, were not significantly different between vitamin E and placebo groups.