Propargylglycine Infusion Effects on Tissue Glutathione Levels, Plasma Amino Acid Concentrations and Tissue Morphology in Parenterally-Fed Growing Rats

Abstract

Amino acid solutions currently used for total parenteral nutrition (TPN) contain little cysteine or cystine. Some premature human infants have low liver activities of gamma-cystathionase and presumably require preformed cysteine or cystine. Growing animals tend to have higher liver gamma-cystathionase activity, which makes them unsuitable as models to study effects of CSH precursors. Because propargylglycine (PPG) inhibits gamma-cystathionase specifically, rats infused with PPG as part of a TPN regimen were evaluated as a potential model. Two groups of rats (120-160 g) were infused for 15 d with TPN regimens, one without and one with PPG (40 mumols/d). A third group received the TPN-control regimen, with methionine added at toxic levels. Propargylglycine treatment significantly decreased plasma cystine and taurine concentrations and significantly increased plasma cystathionine concentration without affecting methionine concentration. Propargylglycine treatment significantly decreased brain, muscle, liver, intestine and stomach glutathione concentration without affecting erythrocyte or heart glutathione concentrations. Electron microscopic examination showed no abnormalities in heart and kidney of PPG-treated rats. Hepatocyte glycogen was lower in TPN-fed controls than in orally fed rats and was further reduced in TPN-PPG-fed animals. Growing rats infused with low doses of PPG show promise as an animal model to study a number of important issues concerning human sulfur amino acid metabolism.