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.

Abstract

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.

• Authors: M A Levy, B Sikorski, T M Bray
• Journal: The Journal of nutrition (J Nutr) Vol. 128 Issue 4 Pg. 671-6 (Apr 1998) ISSN: 0022-3166 [Print] United States
• PMID: 9521626 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dietary Proteins
• Thiazoles
• Thiazolidines
• Glutathione
• Pyrrolidonecarboxylic Acid
• 2-oxothiazolidine-4-carboxylic acid

Topics

• Animals
• Dietary Proteins (therapeutic use)
• Glutathione (metabolism)
• Hyperoxia (pathology)
• Lung (metabolism, pathology)
• Male
• Protein-Energy Malnutrition (diet therapy, pathology)
• Pyrrolidonecarboxylic Acid
• Rats
• Rats, Wistar
• Thiazoles (therapeutic use)
• Thiazolidines