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.
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.
Levy
M A
MA
Department of Human Nutrition, The Ohio State University, Columbus, OH 43210-1295, USA.
Sikorski
B
B
Bray
T M
TM
D000818:Animals; D004044:Dietary Proteins / Q000627:therapeutic use; D005978:Glutathione / Q000378:metabolism*; D018496:Hyperoxia / Q000473:pathology*; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008297:Male; D011502:Protein-Energy Malnutrition / Q000178:diet therapy / Q000473:pathology*; D011761:Pyrrolidonecarboxylic Acid; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000627:therapeutic use*; D053778:Thiazolidines
D004044:Dietary Proteins; D013844:Thiazoles; D053778:Thiazolidines; D005978:Glutathione; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid