Paraquat-induced enhancement of vascular permeability

Paraquat, intradermally injected in the dorsal skin of rats, demonstrated three phasic actions; enhancement of vascular permeability within 30 min (Phase I) and at 6-24 hr after the injection (Phase II) by dye leakage method and bleeding in skin at 2-7 days after the injection (Phase III). Phase I was induced in the presence of paraquat in the skin. However, phases II and III occurred in the absence of paraquat. Morphological study indicated inflammatory observations such as infiltration of mononuclear cells and swelling of venular endothelial cells throughout these three phases. And the most severe morphological changes occurred in phase II. Aspirin, indomethacin, tripelennamine and dexamethasone decreased dye leakage but superoxide dismutase increased it in phase I. These drugs including superoxide dismutase decreased dye leakage in phase II. Bleeding in phase III was decreased by the administration of aspirin and indomethacin. Because of higher effective dose of indomethacin used in this experiment as compared with a clinical dose, aspirin seemed among drugs examined in our experimental models to be the most potent drug that depressed the progression of paraquat-induced enhancement of permeability.