Ascorbic Acid (AA) and Glutathione (GSH) Protect Rat Lung from Chrysotile Asbestos-Induced Oxidative Stress
We reported in earlier studies that the exposure of chrysotile to rat lungs depleted the levels of AA and GSH besides causing fibrosis and hyperplasia around the bronchioles. Based on these observations, we studied the protective role of AA (0.85 mM/day, orally) and GSH (75 μM/day, intraperitoncally) against the asbestos-induced oxidative stress. Rats were treated with AA, GSH, or AA + GSH daily after exposure to a single dose of chrysotile (5 mg, intratracheally) and were sacrificed after 1, 4, 8, and 16 days. Animals either treated with chrysotile or normal saline served as controls. The activities of glutathione peroxidase (GSH-Px), glutathione reductase (GSH-r), catalase, and glucose-6-phosphate dehydrogenase (G-6-PD) were increased significantly in the lung cytosols of chrysotile treated animals, while the levels of GSH and AA were reduced. The levels of H2O2 and lipid peroxidation (LPO) significantly increased in the lung microsomes. Ascorbic acid and GSH alone and in combination did not significantly alter the asbestos-mediated increase in the activities of GSH-Px and GSH-r, but activities of catalase and G-6-PD, and levels of H2O2 and LPO in the lung significantly decreased. In the animals treated with AA or GSH alone or in combination, the levels of these antioxidants were increased. Ascorbic acid and GSH also ameliorated the asbestos-mediated diminution of the activities of phase I and phase II drug metabolizing enzymes. Our data indicate that AA and GSH, being part of a physiologically significant antioxidant system, can prevent some asbestos-induced biochemical events which subsequently may protect lungs against the development of pathological conditions.