Project: Research project

Project Details


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.
Effective start/end date6/1/885/31/92


  • Medicine(all)