The effect of phototherapy on amino acid solutions containing multivitamins

Bhatia, Jatinder; Mims, Le Roy C.; Roesel, Raffaello

doi:10.1016/s0022-3476(80)80829-8

Cited by 41 publications

(20 citation statements)

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“…The etiology of TPNrelated steatosis is multifactorial (2 ), and many nutritional elements have been suspected, such as an amino acid imbalance (3)(4)(5)(6), an excess of glucose or lipids (7 ), or a carbohydrate/nitrogen ratio imbalance (8 ). Oxidative stress (1, 9 -11 ) and products derived from photooxidation of amino acids (9,12 ) have also been proposed. In a previous study (13 ), we reported that in a neonatal animal model on TPN, fatty liver was associated with the infusion of parenteral multivitamin preparations (MVPs), a component of TPN.…”

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confidence: 99%

Association between Hydrogen Peroxide-Dependent Byproducts of Ascorbic Acid and Increased Hepatic Acetyl-CoA Carboxylase Activity

et al. 2005

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Background: Parenteral multivitamin preparation (MVP) induces fatty liver in neonatal guinea pig pups; this is prevented by photoprotection. Photo-excited riboflavin present in MVP generates H2O2 and molecules with masses of 136 and 208. We hypothesized that H2O2 initiates the peroxidation of ascorbic acid (AA), producing biologically active byproducts affecting hepatic lipid metabolism. Methods: Mass spectrometry (MS) documented the participation of H2O2 and photo-excited riboflavin (Ribo) in the formation of AA byproducts. Sixteen 3-day-old guinea pig pups received an intravenous solution (50 g/L dextrose + 4.5 g/L NaCl + 1 kIU/L heparin) at 240 mL · kg−1 · day−1, enriched with control or test mixtures, for 4 days. The control mixture was photo-protected AA + Ribo (without byproducts or H2O2), and the test mixture was AA + Ribo treated to generate AA byproducts without H2O2. Hepatic acetyl-CoA carboxylase (ACC) activity was determined after 4 days. Fourth-day urine samples were analyzed by MS. Data were treated by ANOVA (α = 0.05). Results: H2O2 did not influence the classic degradation of AA, as the generation of 2,3-diketogulonic acid was not affected. In contrast, the formation of molecules with masses of 136 and 208 was H2O2 and time dependent. ACC activity was higher (P <0.01) in animals receiving high concentration of these molecules; its hepatic activation correlated (P <0.01) with the urinary concentration of molecule-208. Conclusions: H2O2 at concentrations found in the clinical setting of total parenteral nutrition induce the transformation of dehydroascorbic acid into compounds that have the potential to affect lipid metabolism. These molecules have peroxide and aldehyde functions.

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Association between Hydrogen Peroxide-Dependent Byproducts of Ascorbic Acid and Increased Hepatic Acetyl-CoA Carboxylase Activity

et al. 2005

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“…12 In the face of immature antioxidant defenses, infused peroxides have the potential to cause an oxidative challenge with general effects or local repercussions at the site of infusion. This is supported by the demonstration that the infusion of an antiperoxide such as bisulfite was associated in parenterally fed infants with a drop in urinary malondialdehyde, 8 a marker of peroxidation…”

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“…Increasing evidence indicates that these sources of oxidants disrupt cell membrane integrity and mediate tissue injury. 9 -11 Furthermore, the oxidation can cause changes in the quality of solutions, 12 as well as loss of potency of parenteral nutrients, because the concentrations of several vitamins and amino acids decrease in TPN solutions exposed to light. 12 In the face of immature antioxidant defenses, infused peroxides have the potential to cause an oxidative challenge with general effects or local repercussions at the site of infusion.…”

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confidence: 99%

“…9 -11 Furthermore, the oxidation can cause changes in the quality of solutions, 12 as well as loss of potency of parenteral nutrients, because the concentrations of several vitamins and amino acids decrease in TPN solutions exposed to light. 12 In the face of immature antioxidant defenses, infused peroxides have the potential to cause an oxidative challenge with general effects or local repercussions at the site of infusion. This is supported by the demonstration that the infusion of an antiperoxide such as bisulfite was associated in parenterally fed infants with a drop in urinary malondialdehyde, 8 a marker of peroxidation 13 .…”

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Admixture of a Multivitamin Preparation to Parenteral Nutrition: The Major Contributor to In Vitro Generation of Peroxides

et al. 1997

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ABSTRACT. Background. Peroxides have been reported to contaminate lipid emulsions and amino acid solutions used in total parenteral nutrition (TPN). This is particularly disturbing in newborn infants who are prone to several diseases related to immature defense mechanisms against oxidative challenges. It is not clear whether the antioxidants in multivitamins help protect parenteral nutrients against the hazards of oxidation.Objective. To evaluate the role of a multivitamin preparation (MVI) on the actual peroxide load received by patients on TPN.Methodology. The generation of peroxides in parenteral nutrition was tested first using test solutions. We compared the relative contribution of commercially available amino acid solutions, a lipid emulsion, and MVI on the level of peroxides in clinically relevant TPN solutions. Second, we measured the level of peroxides actually infused at the bedside. In both circumstances, the effects of time and light exposure were isolated. The level of peroxides was determined by a colorimetric technique and expressed as M equivalents tert-butyl hydroperoxide (M ‫؍‬ TBH).Results. Even when protected from light, the addition of MVI produced a 10-fold increase in peroxides (mean ؎ SEM, n ‫؍‬ 3, 19 ؎ 4 to 189 ؎ 8 M ‫؍‬ TBH at 4 h) in the fat-free TPN solution and a fourfold increase (64 ؎ 6 to 244 ؎ 8 M ‫؍‬ TBH at 4 h) in the lipid-containing TPN solution. A dose-response relationship was found between the concentration of MVI and peroxide levels. The effect of light was the strongest in the presence of multivitamins. The amino acid solutions had a relative inhibitory effect on the generation of peroxides by MVI, which varied (from 54 ؎ 1% to 72 ؎ 1%) all according to the amino acid blend. In parenterally fed premature infants, protecting the intravenous set from light decreased the load of infused peroxides (146 ؎ 15 vs 215 ؎ 24 M ‫؍‬ TBH).Conclusions. The lipid emulsion had a significant but minor additive effect compared with the multivitamin preparation, which was the major contributor to the generation of peroxides. Protection from photooxidation is not sufficient to prevent peroxidation of TPN solutions. Contrary to what one would expect, increasing the concentration of MVI will lead to a greater generation of peroxides, suggesting that the essential antioxidants in MVI do not have antiperoxide properties. Pediatrics 1997;99(3). URL: http://www.pediatrics.org/cgi/content/ full/99/3/e6; amino acids, antioxidants, detergents, lipids, newborn infants, oxidation, parenteral nutrition.ABBREVIATIONS. TPN, total parenteral nutrition; TBH, tert-butyl hydroperoxide; PN, fat-free and vitamin-free parenteral nutrition; MVI, multivitamin preparation.Isolated constituents of total parenteral nutrition (TPN) represent a potential source of oxidants. Because lipids infused with TPN solutions are contaminated by peroxides, 1,2 these emulsions are often believed to be the major source of oxidants in solutions of parenteral alimentation. However, other nutrients can promote peroxidation such as a...

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“…TPN-related hepatic dysfunctions (25) have been linked to oxidant stress (26,27) as well as genetic (28,29), nutritional, environmental, and inflammatory factors (23). More specifically, the following nutritional factors have been associated with steatosis and/or cholestasis: enteral starvation (30,31), an amino acid imbalance (32,33), photo-oxidized products of amino acids (11,12,34), an excessive infusion of glucose (35) or lipids (36), a carbohydrate to nitrogen imbalance (37,38), and the source of infused lipids (39).…”

Section: Discussionmentioning

confidence: 99%

Photooxidation of Parenteral Multivitamins Induces Hepatic Steatosis in a Neonatal Guinea Pig Model of Intravenous Nutrition

Chessex

2002

Pediatric Research

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Photooxidation of multivitamin solutions results in the generation of peroxides. Because peroxides are associated with hepatic steatosis and fibrosis as well as cholestasis, we questioned whether multivitamins are implicated in hepatic complications of parenteral nutrition. Guinea pig pups were assigned to groups receiving intravenously either total parenteral nutrition, photo-protected or not, or a control solution (5% dextrose ϩ 0.45% NaCl) supplemented with either a) multivitamins; b) photo-protected multivitamins; c) multivitamins without riboflavin; or d) peroxides (H 2 O 2 , tert-butylhydroperoxide). After 4 d, liver was sampled for histology and isoprostane-F 2␣ levels, a marker of radical attack. Multivitamins as well as total parenteral nutrition were associated with steatosis (scored 0 -4), the severity of which was reduced (p Ͻ 0.05) by photo protection. Although H 2 O 2 is the major peroxide contaminating multivitamins, it did not induce steatosis scores different than the controls. Compared with controls, hepatic isoprostane-F 2␣ content increased in animals infused with H 2 O 2 (p Ͻ 0.05), but not in those infused with Multi-12 pediatric multivitamins or total parenteral nutrition. Results suggest that peroxides and/or free radicals are not mediators of the induction of steatosis observed with infusion of photo-exposed multivitamins, as there was no correspondence between histologic findings and hepatic levels of isoprostanes. It is suspected that a component of the multivitamin solution becomes hepato-toxic after photo-exposure, as indicated by the protective effect observed when withdrawing riboflavin. Photooxidation of multivitamins might be the common link between reports involving amino acids, lipids, and light exposure in the ethiology of hepatic complications of parenteral nutrition. Exposure of TPN solutions to light is linked to alterations in hepatobiliary function and histology in a perfused liver model (1) as well as in vivo (2). In the presence of light, the parenteral multivitamin preparation is the site of reactions between oxygen and electron donors, resulting in the generation of peroxides. Hydrogen peroxide (H 2 O 2 ), which is regarded as a key element in the oxygen toxicity of the cell, represents over 80% of peroxides generated in multivitamins (3). Organic peroxides have also been reported to contaminate solutions of parenteral nutrition (3-6). In parenterally fed neonates, the exposure of multivitamins to daylight is associated with an infused peroxide load and its urinary excretion (7). Peroxides have been linked to hepatic steatosis (8) and fibrosis (9), as well as cholestasis (10). Multivitamins and peroxides induce the same oxidant response in the lungs of guinea pig pups (11). The relative liver weight of these animals was 40% higher than controls (12), and histology revealed the presence of hepatic steatosis. We hypothesize that multivitamins might account for part of the role of light in TPN-related liver complications.Because of the catalytic role of photo-excited rib...

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The effect of phototherapy on amino acid solutions containing multivitamins

Cited by 41 publications

References 11 publications

Association between Hydrogen Peroxide-Dependent Byproducts of Ascorbic Acid and Increased Hepatic Acetyl-CoA Carboxylase Activity

Association between Hydrogen Peroxide-Dependent Byproducts of Ascorbic Acid and Increased Hepatic Acetyl-CoA Carboxylase Activity

Admixture of a Multivitamin Preparation to Parenteral Nutrition: The Major Contributor to In Vitro Generation of Peroxides

Photooxidation of Parenteral Multivitamins Induces Hepatic Steatosis in a Neonatal Guinea Pig Model of Intravenous Nutrition

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