Although trace element levels in human tissue account for < 0.01% of total organism mass, these components are vital for human growth and development. For enteral feeding, subjects derive adequate trace elements through diversified diets, enteral nutrition products, and oral drug products. For PN, due to chemical molecule stability, a variety of complex drug products containing multi-trace elements are required to meet clinical needs. MTEI-(I) is a complex drug product containing multi-trace elements specially developed for children. It supplements six trace elements such as Zn, Cu, Mn, Se, fluorine (Fl), and iodine (I), but not Fe or Cr, to meet guideline requirements for the addition of trace elements during PN[2, 3].
Inflammatory mechanisms generated by inflammation and oxidative stress responses from free radical accumulation often cause normal proteins, lipids, and nucleic acids to attack, undermine, and destroy normal physiological functions. Trace elements are required for the regulation of substance metabolism, enzyme catalytic activity, etc., and thus affect inflammation and oxidative stress mediators. For example, during oxidative stress and inflammation, trace element distribution will be altered, thus a reasonable intake of these elements will exert positive effects towards inflammation control, and slow or reduce oxidative stress responses. In previous studies, it was shown that appropriate Cu, Zn and Se levels reduced free radicals, enhanced antioxidant capacity, and regulated inflammatory reactions [7–9], while Cu was positively correlated with bacterial levels and inflammatory markers[10, 11] ,and Zn and Se were negatively correlated with inflammation and oxidative stress[12, 13]. Supplementation with Zn improved high Cu-Zn ratios in blood, reduced oxidative stress, improved inflammatory conditions, and maintained immune functions. These data were consistent with our findings suggesting that Cu was decreased, and Zn and Se were increased after PN treatment, with trace element differences in Group B more significant. Equally, we observed that WBC levels in both groups were decreased after PN treatment, with levels in Group B significantly decreased after PN treatment (p = 0.011). This observation suggested that the appropriate high-dose administration of I was effectively controlling inflammation and antioxidation.
Hexacosanoic acid is a very long chain fatty acid, and is an important component of phospholipid molecules. In a previous study, these molecules were shown to play important roles in cellular biochemical reactions, nutrient storage, and intercellular communications. Due to homeostatic imbalances between molecular transport and utilization, excessive fatty acid accumulation may cause toxicity in some tissues, which becomes manifested as oxidative stress and inflammation, potentially culminating in cell apoptosis. Several studies reported that very long chain fatty acids induced the production of reactive oxygen species in the SK-N-BE neuroblastoma cell line, and enhanced oxidative stress. Gursev et al. observed these molecules activated nicotinamide adenine dinucleotide phosphate oxidase activity, and enhanced superoxide anion-mediated lipid peroxidation in skin fibroblasts. In this study, we observed that the β-oxidation of very long chain fatty acids (hexacosanoic acid) was significantly reduced in Group B (p༜0.05), indicating subjects were less prone to oxidative damage caused by lipid peroxidation. Therefore, appropriate high-dose administration of I exerted positive antioxidation effects in this group.
Stress has an important impact on various metabolic pathways. Under stress conditions, the following metabolic characteristics are often observed; high metabolic rate, increased catabolism, and reduced anabolic metabolism, resulting in a negative balance in overall metabolism. In this study, 37 children were under acute stress after surgery or disease. Chen Weiqiang et al. observed that stress induced the loss of Zn from the body, whereas Zn supplementation exerted protective effects. In this study, after supplementing I, we observed that valine, leucine, isoleucine degradation, taurine and hypotaurine metabolism, arginine and proline metabolism, and other amino acid metabolism were all reduced, suggesting a benefit to disease recovery. Equally, ketone metabolism was also reduced, suggesting the high metabolic rate had been relieved. Of these components, β-oxidation of very long chain fatty acids, pentose phosphate metabolism, ketone body metabolism, citric acid cycle and pyruvate metabolism were all significantly reduced in Group B. These factors were related to energy metabolism[21, 22], indicating that appropriate high-dose administration of I was helpful in relieving stress induced elevated metabolism.
Hypoxia is a basic pathological process implicated in several diseases. Severe hypoxia induces considerable cellular harm, and often leads to death. Kim et al.observed that Zn ameliorated hypoxic neuronal death induced by deferoxamine (DFX) and sodium azide (NaN3). Xinge et al. reported that Zn chelating agents had protective effects towards hypoxic ischemic brain damage in zebrafish. Kun et al. proposed that exogenous Zn had protective effects towards hypoxic neurons. Hypoxanthine is a naturally occurring purine derivative and is the major catabolite of adenosine triphosphate (ATP) in hypoxic or ischemic tissue. In general terms, a large increase in hypoxanthine levels in bodily fluids indicates ATP depletion . In a trial of subjects with critical illness, burns and burn-induced sepsis , the evidence suggested that elevated ATP associated degradation products i.e., adenosine, inosine, hypoxanthine, and xanthine were associated with tissue hypo-perfusion and hypoxia levels. Therefore, it was suggested that purine metabolites such as xanthine and hypoxanthine are potential markers of tissue hypoxia. In our study, the administration of I in Group B significantly increased plasma Zn levels. In our metabolomics study, we observed that purine metabolism in Group B was significantly reduced, and related metabolites were similarly reduced, indicating that appropriate high-dose administration of MTEI-(I) improved hypoxic conditions in these subjects.