Intravenous eugenol causes hemorrhagic lung edema in rats: proposed oxidant mechanisms

Although eugenol, the active phenolic constituent of oil of cloves, has been implicated as a cause of noncardiogenic pulmonary edema, the mechanism of lung injury is unknown. We studied the effects of intravenous infusion of eugenol in rats and found that 4 microliters and 8 microliters of eugenol (6.52 mol/L) caused acute respiratory distress with hemorrhagic pulmonary edema. Histologic features included perivascular, interstitial, and alveolar edema with extravasation of red blood cells and neutrophils into the alveolar space and alveolar capillary trapping of neutrophils. In addition, lungs treated with eugenol had increased bronchoalveolar lavage fluid (BALF) protein content, and lung wet-to-dry weight ratios were increased in animals treated with 8 microliters eugenol. Pretreatment with intravenous superoxide dismutase (SOD) or catalase but not dimethylthiourea (DMTU) decreased BALF protein content after infusion of 4 microliters and 8 microliters of eugenol. SOD and catalase but not DMTU decreased lung wet-to-dry weight ratios in animals infused with 8 microliters of eugenol. We conclude that intravenous infusion of eugenol causes hemorrhagic pulmonary edema with intrapulmonary sequestration of neutrophils and suggest that the injury may be at least partly oxidant mediated.