Pathological consequences to reticuloendothelial system organs following infusion of unstable all-in-one mixtures in rats

Abstract

Recent evidence of lung injury from the infusion of unstable lipid injectable emulsions as all-in-one mixtures (AIOs) was shown in a guinea pig infusion model. We extended this research to a Sprague-Dawley rat infusion model, focusing our analyses on the dose of large-diameter fat globules (expressed as the volume-weighted percent of fat larger than 5 or 10 microm, PFAT5 or PFAT10) from the dispersed phase of emulsion mixtures of varying levels of stability, and the potential injurious effects on major tissues of the reticuloendothelial system (i.e., lungs and liver). Two identical infusion experiments (n=13 rats/study), involving stable (s-AIO) vs. unstable (u-AIO) mixtures were separately conducted, and differed in two respects: (1) duration of AIO infusion (24 h vs. 72 h) and, (2) starting PFAT5 levels for the u-AIO (24- vs. 72-h PFAT5: 0.682+/-0.055% vs. 0.117+/-0.024%, respectively). In both experiments, s-AIOs vs. u-AIOs were infused, and evidence of hepatic oxidative stress was noted by significantly higher tissue concentrations of malondialdehyde (MDA) during infusion of u-AIOs. The higher concentrations of MDA in the livers of animals receiving the u-AIOs were also accompanied by significantly higher plasma concentrations of AST in both infusion experiments suggesting injury. Levels of cytokines (IL-1beta, TNFalpha) in the lungs and livers in both infusion studies were variable. These results demonstrate the infusion of u-AIOs with starting PFAT5 levels of approximately 0.1% show evidence of pathological consequences to the liver and lungs, and therefore, such unstable AIO mixtures should probably be avoided in the clinical setting.