Attenuation of silica-induced cytotoxicity by lazaroid (U-75412E).
Vallyathan-V; Huang-SH; Leonard-S
Toxicologist 1996 Mar; 30(1)(Part 2):97
Lazaroids (21-aminosteroids) are potent scavengers of oxygen radicals (OR) and inhibitors of lipid peroxidation. They have been shown to provide protection from OR induced injury. Crystalline silica (silica) a potent cytotoxic agent is known to cause pulmonary fibrosis in animals and man. We have shown previously that ORs are involved in silica-induced pulmonary injury and inflammation. In the present study, we investigated the effectiveness of lazaroid (U-75414E) in the amelioration of silica-induced cytotoxicity in rat alveolar macrophages (AM). To test the efficacy of lazaroid in attenuating in vitro silica-induced cytotoxicity, we measured lactate dehydrogenase, N-acetyl glucaminidase, superoxide dismutase, glutathione peroxidase, and hydrogen peroxidase release from AMs as indicators of cytotoxicity in the presence and absence of lazaroid. We also studied the ability of lazaroid to scavenge hydroxyl radicals (OH) generated by silica from hydrogen peroxide. Lazaroid protected AMs from silica-induced cytotoxicity and injury. Lazaroid also exhibited a dose dependent ability to scavenge OH. Results of these in vitro studies suggest that administration of lazaroid in silica-induced lung injury may protect the lung against oxidant injury.
Silicates; Silica-dusts; Cytotoxins; Cytotoxicity; Cytotoxic-effects; Fibrosis; Pulmonary-system-disorders; Lung-fibrosis; Lung-disorders
The Toxicologist. Society of Toxicology 35th Annual Meeting, March 10-14,1996, Anaheim, California