Antioxidant protects against lung damage in silicosis

These results appear in the second issue for October 2006 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

Yoshiaki Ishigatsubo, M.D., Ph.D., of the Department of Internal Medicine and Clinical Immunology at Yokohama City University in Japan, and 11 associates studied 46 male patients with silicosis, an inflammatory disorder caused by inhaling crystalline silica for prolonged periods. The study included 27 male patients with chronic obstructive pulmonary disease and 27 healthy male volunteers as controls. The investigators also studied a mouse model of silicosis.

Silicosis results from exposure to crystalline silica in mines and foundries, at sand blasting operations and at stone, clay, and glass manufacturing plants. Crystalline silica induces the production of reactive oxygen species, which can cause scar tissue to develop in the lungs.

About 1 million workers are believed to have been exposed to silica dust in the U.S. More than 10,000 silicosis patients are currently being followed in Japan.

“Pulmonary HO-1 expression is increased in silicosis,” said Dr. Ishigatsubo. “HO-1 suppresses reactive oxygen species activity, and its subsequent pathologic changes, thereby reducing disease progression.”

The researchers noted that their work was the first to demonstrate that HO-1 is synthesized in the lungs of patients with silicosis, thus contributing to a significant elevation of serum HO-1 levels in these patients.

“Silica particles were consistently associated with lesions containing HO-1 expressing cells,” added Dr. Ishigatsubo. “The number of HO-1-expressing cells was significantly higher in patients with silicosis than in control subjects.”

The investigators said that their present results indicate that silicosis patients' serum HO-1 levels correlate significantly with their primary lung function test level and vital capacity. (Vital capacity is the maximum amount of air that can be exhaled after a maximum inhalation, showing the status of lung tissue.)

The authors believe that if serum HO-1 derives primarily from lung lesions, it could also represent a novel biomarker for evaluating the severity of silicosis.

In their mouse studies, hemin, a potent inducer of HO-1, suppressed acute inflammation after silica exposure, whereas zinc protoporphyrin, an inhibitor of HO-1, accelerated the development of silicosis lesions.