Stimulation of Antioxidants Protects Against Emphysema in Mice

Cigarette smoke induces reactive oxygen species in lung tissue. Nevertheless, prior attempts to protect the lungs using antioxidants (e.g., N-acetylcysteine) have been disappointing.

A team from Johns Hopkins developed a small molecule, CDDO-imidazolide (CDDO-Im), that activates the gene for a transcription factor (Nrf2). Nrf2, in turn, activates multiple genes that encode antioxidants and cytoprotective enzymes. Mice were exposed to cigarette smoke for 6 months; half of them were fed CDDO-Im during the smoke-exposure period. The CDDO-Im mice exhibited much less oxidative stress in their lungs, less alveolar cell death and alveolar destruction, and less pulmonary hypertension than did the smoke-exposed control group. Mice in which the gene f…