Inhibition by antilipoxygenase drugs of cellular chemiluminescence in silica activated phagocytic cells-alveolar macrophages, human neutrophils and human leukemia (HL-60) cells.
Gutierrez-J; Dyke-K; Wu-L; Vallayathan-V; Castranova-V
Proceedings of the 3rd Symposium on Respirable Dust in the Mineral Industries, Pittsburgh, Pennsylvania, October 17-19, 1990. Frantz RL, Ramani, RV, eds., Littleton, CO: Society for Mining, Metallurgy, and Exploration, 1990 Oct; :171-178
The inhibitory effects of the drugs A63162 and AA861, the free radical scavenger nordihydroguaiaretic-acid (NDGA), and the indirect inhibitor tetrandrine (TA) on silica (14808607) activated lipoxygenase in human neutrophils and leukemia (HL-60) cells and in rat alveolar macrophages was studied. Lipoxygenase inhibition was determined by inhibition of peroxide free radical luminol chemiluminescence (CL) over a 20 minute period. Almost total inhibition of CL was observed when neutrophils were silica activated in the presence of A63162, but only modest inhibition was seen with AA861. It was noted that CL in neutrophils was mainly due to myeloperoxidase, not lipoxygenase. In dimethyl-sulfoxide differentiated HL-60 having no myeloperoxidase system, 2x10(-6) molar (M) TA produced 33% CL inhibition. At concentrations of 2x10(- 5)M, A63162 inhibited CL 50%, while AA861 and NDGA gave slightly higher inhibitions. In rat alveolar macrophages, NDGA completely inhibited CL, A63162 inhibited CL by 50% and AA861 was the least inhibitory. A soybean lipoxygenase assay was used to demonstrate that TA had no direct effect on lipoxygenase. In multiple HL-60 cell comparative assays, NDGA achieved 85% inhibition, and A63162 and TA each achieved 42% inhibitions of CL. Similar assays using neutrophils determined NDGA to be completely inhibitory, while A63162 and TA inhibited CL by 22% and 10%, respectively. The authors conclude that, while NDGA may be too toxic, the other antilipoxygenase drugs tested may be effective in the treatment of silicosis
Enzyme-inhibitors; Lung-cells; Alveolar-cells; In-vitro-studies; Pulmonary-system-disorders; Lung-disorders; Mammalian-cells; Lung-disease
Proceedings of the 3rd Symposium on Respirable Dust in the Mineral Industries, Pittsburgh, Pennsylvania, October 17-19, 1990