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

Abstract

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 + 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(2alpha) 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 < 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(2alpha) content increased in animals infused with H(2)O(2) (p < 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. Photo-oxidation 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.

Light-Induced Byproducts of Vitamin C in Multivitamin Solutions

“…Faced with problems linked to the immature antioxidant defenses of premature newborn infants, clinicians might be tempted to increase the infusion of multivitamin solutions because they contain antioxidant vitamins that have documented antiradical properties (18,19 ). However, this process could increase the infusion of these byproducts of vitamin C. The present study confirms the findings of Silvers et al (13 ) that the concentration of ascorbic acid decreases within minutes after exposure to light (Fig.…”

Increased Incidence of Parenteral Nutrition-Associated Cholestasis with Aminosyn PF Compared to Trophamine

“…3 Many of the proposed risk factors for PNAC have been recently reviewed, 4,5 and include low birth weight, prematurity, duration of PN, lack of enteral intake, sepsis, enzyme deficiencies, genetic causes, quantity or quality of amino-acid intake, excess of nonprotein caloric intake, and trace mineral toxicity. Male gender, 6 perinatal depression or shock, 7 and more recently, phototoxicity of parenteral multivitamin supplements, 8 and toxicity from plant phytosterols 9 have also been implicated as potential risk factors for PNAC. Although several of these risk factors are unavoidable, research is still needed to define the optimal parenteral amino-acid solution for pediatric and neonatal patients, 10 one that would allow normal growth and development, result in normal serum aminoacid levels, and cause a minimum of unwanted side effects, such as cholestasis.…”

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

“…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. We suspected an ingredient of MVP that might be generated during light exposure.…”