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Amifostine Pre-treatment Attenuates Lung Injury, But Not Inflammation, in Rats Intracheally Instilled with Particulate Matter Rich in Transition Metals
Citation:
FARRAJ, A., D. W. WINSETT, N. HAYKAL-COATES, M. S. HAZARI, A. P. CARLL, C. LAMB, AND D. L. COSTA. Amifostine Pre-treatment Attenuates Lung Injury, But Not Inflammation, in Rats Intracheally Instilled with Particulate Matter Rich in Transition Metals. Presented at Annual American Thoracic Society, San Diego, CA, May 15 - 20, 2009.
Impact/Purpose:
We hypotesized that amifostine will attenuate PM-induced increases in cardiopulmonary and systemic markers of inflammation and toxicity. High dose AMF pre-treatment significantly attentuated particulate matter-induced increases in lung protein and caused trends towards decreases in lung LDH and albumin, but had no effect on neutrophilic infiltration. Amifostine may have utility in mitigating some of the adverse health effects associated with exposure to air pollution.
Description:
Exposure to particulate matter (PM) is associated with increased cardiovascular disease morbidity and mortality. These correlations are strengthened in individuals with pre-existing cardiovascular disease, including hypertension. Extensive evidence supports a significant role for oxidative stress in the pulmonary and cardiovascular injury resulting from PM exposure. Accordingly, antioxidant supplementation has been investigated as a prophylactic means of minimizing the deleterious effects of air pollution inhalation. Amifostine (AMF) is a well-known anti-oxidant used in clinical oncology to ameliorate oxidative stress-driven side effects that result from radiation and anti-neoplastic therapeutic drug treatment, but has not been investigated as an intervention in air pollution studies. We hypothesized that AMF will attenuate PM-induced increases in cardiopulmonary and systemic markers of inflammation and toxicity. Spontaneously hypertensive rats were administered 50 or 200 mg/kg AMF (ip) in saline vehicle or vehicle alone, and then one hour later intratracheally instilled with 1 mg/kg of residual oil fly ash (ROFA; an emission source particle rich in transition metals) in saline vehicle or vehicle alone. ROFA instillation caused a significant increase in several markers of injury, edema, and inflammation in the lung including lactate dehydrogenase (LDH), protein, albumin, and neutrophils relative to corresponding saline-instilled rats. High dose AMF pre-treatment significantly attenuated ROFA-induced increases in lung protein and caused trends towards decreases in lung LDH and albumin, but had no effect on neutrophilic infiltration. There was no significant effect of low dose AMF. Amifostine may have utility in mitigating some of the adverse health effects associated with exposure to air pollution (This abstract does not reflect EPA policy).