Correlation between lipid peroxidation and morphological manifestation of paraquat-induced lung injury in rats

Biochemical and morphological studies of rat lung were performed to determine the role of lipid peroxidation in the in vivo lung toxicity of paraquat. Two injections of 20 mg/kg paraquat were administered intraperitoneally every other day. While notable epithelial damage in the lungs was observed on the day after the second paraquat injection and progressed through the 5th day, the concentration of lipid peroxides in the rat lungs did not increase by the 3rd day after the injection. The lipid peroxide concentrations increased after the 5th day post-injection, and reached the maximum concentrations on the 7th day, when the damaged alveolar surface had been mostly repaired by regenerative pneumocytes. On the other hand, the delayed increase of lung lipid peroxides in paraquattreated rats paralleled the increased number of macrophages in the lung, which reached maximum numbers on the 7th day. Glutathione peroxidase activity in the lungs also increased with a similar time course. Macrophages from the lungs contained a large amount of engulfed degradation products and cellular debris, and immunohistochemical study showed high glutathione peroxidase content on the 5th and 7th days. These results suggest that lipid peroxidation is a relatively late event in the in vivo paraquat-treated lung and that the delayed increase of lipid peroxides in the lungs occurs from the phagocytic activities of macrophages rather than from toxic cell injury.