Inhibition of chlorine-induced lung injury by the type 4 phosphodiesterase inhibitor rolipram

Journal Article · Sat Sep 01 04:00:00 EDT 2012 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2012.06.017· OSTI ID:22215902

Chang, Weiyuan; Chen, Jing; Schlueter, Connie F. ^[1]; Rando, Roy J. ^[2]; Pathak, Yashwant V. ^[3]

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1. Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States)
2. Department of Environmental Health Sciences, School of Public Health and Tropical Medicine, Tulane University Health Sciences Center, New Orleans, LA (United States)
3. College of Pharmacy, University of South Florida, Tampa, FL (United States)

Chlorine is a highly toxic respiratory irritant that when inhaled causes epithelial cell injury, alveolar-capillary barrier disruption, airway hyperreactivity, inflammation, and pulmonary edema. Chlorine is considered a chemical threat agent, and its release through accidental or intentional means has the potential to result in mass casualties from acute lung injury. The type 4 phosphodiesterase inhibitor rolipram was investigated as a rescue treatment for chlorine-induced lung injury. Rolipram inhibits degradation of the intracellular signaling molecule cyclic AMP. Potential beneficial effects of increased cyclic AMP levels include inhibition of pulmonary edema, inflammation, and airway hyperreactivity. Mice were exposed to chlorine (whole body exposure, 228–270 ppm for 1 h) and were treated with rolipram by intraperitoneal, intranasal, or intramuscular (either aqueous or nanoemulsion formulation) delivery starting 1 h after exposure. Rolipram administered intraperitoneally or intranasally inhibited chlorine-induced pulmonary edema. Minor or no effects were observed on lavage fluid IgM (indicative of plasma protein leakage), KC (Cxcl1, neutrophil chemoattractant), and neutrophils. All routes of administration inhibited chlorine-induced airway hyperreactivity assessed 1 day after exposure. The results of the study suggest that rolipram may be an effective rescue treatment for chlorine-induced lung injury and that both systemic and targeted administration to the respiratory tract were effective routes of delivery. -- Highlights: ► Chlorine causes lung injury when inhaled and is considered a chemical threat agent. ► Rolipram inhibited chlorine-induced pulmonary edema and airway hyperreactivity. ► Post-exposure rolipram treatments by both systemic and local delivery were effective. ► Rolipram shows promise as a rescue treatment for chlorine-induced lung injury.

• OSTI ID: 22215902
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 2 Vol. 263; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMP
CHLORINE
DIFFUSION BARRIERS
EDEMA
INFLAMMATION
INHIBITION
INJURIES
LUNGS
MICE
NEUTROPHILS
PROTEINS
TOXICITY