It has become recognized that enhancing the
antioxidant defense system during the early phase of rehabilitation is important to the survival of wasting
protein-energy malnourished (PEM) patients. In this study, we compared the efficacy of
dietary protein replenishment and supplementation with
L-2-oxothiazolidine-4-carboxylate (OTC, 3.5 mg/d), a
cysteine precursor, to protect against
hyperoxia-induced lung damage in PEM rats. The PEM rats were produced by feeding weanling rats a
protein-deficient diet (0.5%
protein) for 14 d. PEM rats were then divided in three dietary treatment groups, 0.5%
protein (-Pr), 0.5%
protein plus the OTC supplement (+OTC), or 15%
protein (+Pr) during 4 d of either
hyperoxia (85% O2) or air exposure. Increased lung-to-
body weight ratios, indicative of oxidative tissue damage, were observed following exposure to
hyperoxia in -Pr and +Pr rats, but not in +OTC rats, even though the OTC supplement and the 15%
protein diet contained a comparable amount of
cysteine. Tissue
reduced glutathione (GSH) status, GSH-dependent
enzyme activity and
antioxidant defense
enzyme activities were monitored in the lung, liver and blood during 4 d of
hyperoxia exposure. OTC supplementation enhanced GSH levels significantly in the lung of PEM rats, whereas
protein repletion significantly elevated blood GSH concentrations. The protective effect of OTC was not a function of changes in activity of GSH-dependent
enzymes or
oxygen defense
enzymes in the lung. These results indicate that a short-term strategy that selectively elevates GSH levels in the lung is more effective than
protein repletion in protecting against
hyperoxia-induced oxidative lung damage in PEM rats.