Lipid peroxidation of intravenous fat emulsions: a pharmaceutical issue with clinical impact?

Abstract

Oxidative balance and antioxidant defense mechanisms are of increasing interest in the research of life-threatening pathologies and organ dysfunctions. Lipid peroxidation and, in particular, free radicals, may modulate or disturb the basal metabolism and functional state of cells and organs and therefore may be a critical factor in progression or resolution of disease.1 Possible (per)oxidation-related injuries include necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy. Parenteral nutrition (PN) administered as all-in-one (AIO) admixtures has proved to be beneficial and a major contributor to the efficient, safe, and economic treatment or prevention of malnutrition in properly selected patients often affected by severe illness. Lipid emulsions are an essential element of PN regimens. However, due to the amount of polyunsaturated fatty acids (PUFAs) in lipid emulsions, there is concern that chemical degradation and harmful hydroperoxide formation may occur.2 A few studies in humans, especially in preterm infants, assessed the extent of peroxidation in parenteral fat emulsions and showed the toxic risk of degraded lipid components in vivo.3 Differences between the fatty acid pattern of intravenous lipids used for clinical nutrition and the physiologic lipid fraction of blood are obvious. The high concentration of PUFAs, forming . 50% of the total fatty acid content in long-chain triacylglycerol-based (LCT) fat emulsions, is of special interest for clinicians and pharmacists. PUFAs are essential for structural and metabolic functions of the human organism and they also have an important modulating function on the inflammatory and immunologic response to acute or chronic disease. Dependent on the ratio of v-3 (a-linolenic acid) to v-6 (linoleic acid) PUFAs, different metabolic pathways exist to form kinins and biologic mediators. Increasing the v-3/v-6 ratio in humans leads, through elongation of the individual fatty acids, to enhanced synthesis of v-3 eicosanoids and its related mediators. These mediators compete with highly active v-6 eicosanoid derivatives (prostaglandins, thromboxanes, and leukotrienes). The latter are characterized by potent vasoactive, bronchoactive, and chemotactic properties. The pharmacologic actions of PUFA metabolites are further modified by the presence and formation of lipid peroxides. Lipid peroxidation is a free-radical-mediated autocatalytic breakFIG. 1. Lipid peroxidation.