Histopathologic study of adverse effects of linoleic acid on rat lung.

Linoleic acid administered intravenously was highly toxic to the rat lung. The severity of the toxicity paralleled the dosage administered and was characterized by generalized, irreversible damage to alveolar wall structures. Although evidence of tissue damage was not apparent or minimal by light microscopy, ultrastructural studies disclosed extensive degeneration and necrosis of septal wall components with 15 minutes following injection of low dosages of linoleic acid. Degeneration of endothelial cells was most severe suggesting that these cells were the target of injury resulting in impaired vascular integrity, interstitial and alveolar edema, and degeneration of type 1 pneumocytes. Fragmentation and stripping of endothelium from capillary basement membranes was uniformly present and was in some instances associated with platelet aggregation indicative of early thrombosis. These studies suggest that this toxic effect on septal capillaries leading to increased permeability and alveolar edema may be a contributing factor to death occurring from free fatty acid toxicity in the human.