Hepatic abnormalities occur frequently during the administration of total parenteral nutrition (TPN) in both infants and adults. In vivo studies indicate a role for amino acids in the induction of TPN-associated hepatic dysfunction, but the mechanisms involved are unknown. Our preliminary data indicate that the interaction of TPN constituents with light results in photoproducts which alter hepatic function in both human premature infants and in rats. The detrimental photooxidation processes could be initiated when the TPN solutions are exposed to light, particularly the intense ambient light in neonatal nurseries, or when the solutions are in prolonged contact with photosensitizers such as vitamins. The proposed studies will test the hypothesis that parenteral nutrients (amino acids, glucose and vitamins) are photooxidized to hepatotoxic products by prolonged exposure to light and/or contact with photosensitizing vitamins. The studies in infants will determine if prevention of TPN exposure to light or prolonged interaction of TPN constituents with vitamins will decrease the frequency or severity of TPN-associated hepatic dysfunction. Parallel studies in rats will allow manipulation of the nutrient components and examination of more comprehensive biochemical and histologic outcome measures. Premature infants will receive parenteral nutrition in the presence or absence of light and/or light exposed vitamins. Outcome measures will include serum bile acids, gamma glutamyl transferase, leucine aminopeptidase and plasma amino acids. Rats will be given nutrients to parallel and extend human studies and outcome measures will include bile flow, bile acid secretion, biliary gamma glutamyl transferase, biliary solute excretion; plasma, liver and biliary amino acids, serum bile acids; and liver histology, histochemical studies of bile canaliculi localized enzymes and ultrastructure. Subsequent studies will involve irradiating amino acids arbitarily divided into groups based on susceptibility to photoxidation, and determining their effects on hepatic function. This approach will allow us to identify a group of amino acids whose light-mediated photooxidation leads to hepatotoxic products. Single amino acids within a toxic group will be irradiated and studied as before. Photooxidation products of hepatotoxic amino acid(s) will then be identified by HPLC, UV- and infrared spectroscopy, mass spectroscopy and nuclear magnetic resonance. These studies will result in the characterization of patterns and specific sites of TPN-associated hepatic injury and identification of specific amino acid photoproducts leading to such injury or dysfunction.

Project Start
1988-06-01
Project End
1991-05-31
Budget Start
1988-06-01
Budget End
1989-05-31
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555
Moslen, M T; Kanz, M F; Bhatia, J et al. (1994) Biliary glutathione and some amino acids are markedly diminished when biliary pressure is elevated. Exp Mol Pathol 61:1-15
Bhatia, J; Moslen, M T; Haque, A K et al. (1993) Total parenteral nutrition-associated alterations in hepatobiliary function and histology in rats: is light exposure a clue? Pediatr Res 33:487-92
Moslen, M T; Kanz, M F; Bhatia, J et al. (1992) Biliary endogenous inorganic phosphate, D-glucose, IgA and transferrin are differentially altered by hydrostatic pressure. J Hepatol 16:89-97
Bhatia, J; Rivera Jr, A; Moslen, M T et al. (1992) Hepatic function during short-term total parenteral nutrition: effect of exposure of parenteral nutrients to light. Res Commun Chem Pathol Pharmacol 78:321-40
Bhatia, J; Moslen, M T; Kaphalia, L et al. (1992) Glutathione and tissue amino acid responses to light-exposed parenteral nutrients. Toxicol Lett 63:79-89
Bhatia, J; Rassin, D K; McAdoo, D J (1991) Photosensitized oxidation of tryptophan: effect on liver and brain tryptophan. JPEN J Parenter Enteral Nutr 15:637-41
Bhatia, J; Rassin, D K; Cerreto, M C et al. (1991) Effect of protein/energy ratio on growth and behavior of premature infants: preliminary findings. J Pediatr 119:103-10
Bhatia, J; Rassin, D K (1991) Feeding the premature infant after hospital discharge: growth and biochemical responses. J Pediatr 118:515-9
Cho, F; Bhatia, J; Rassin, D K (1990) Amino acid responses to dietary intake in the first 72 hours of life. Nutrition 6:449-55