Selective Elevation of Glutathione Levels in Target Tissues with L-2-Oxothiazolidine-4-Carboxylate (OTC) Protects against Hyperoxia-Induced Lung Damage in Protein-Energy Malnourished Rats: Implications for a New Treatment Strategy

Manuscript received 18 April 1997. Initial reviews completed 18 August 1997. Revision accepted 8 December 1997.

Department of Human Nutrition, The Ohio State University, Columbus, OH 43210-1295 and ^* Department of Nutritional Sciences, University of Guelph, Guelph, ON, Canada, N1G 2W1

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.

The Journal of Nutrition Vol. 128 No. 4 April 1998, pp. 671-676
Copyright ©1998 by the American Society for Nutritional Sciences

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