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L-2-Oxothiazolidine-4-Carboxylate, a Cysteine Precursor, Stimulates Growth and Normalizes Tissue Glutathione Concentrations in Rats Fed a Sulfur Amino Acid-Deficient Diet^1,2,

Ajey Jain^*, David C. Madsen, Peter A. M. Auld^*, William W. Frayer^*, Morton K. Schwartz^**, Alton Meister and Johannes Mårtensson^,**,,3

The^* Perinatology Center/Department of Pediatrics Department of Biochemistry, Cornell University Medical College, New York, NY 10021 ^** Department of Clinical Chemistry, Memorial Sloan Kettering Cancer Center, New York, NY 10021 Clintec Technologies, Deerfield, IL 60015-0760 Department of Internal Medicine, Greenwich Hospital/Yale University School of Medicine, Greenwich, CT 06830

The efficiency of L-2-oxothiazolidine-4-carboxylate, a cysteine precursor, in stimulating glutathione synthesis and growth was evaluated in growing rats. Animals were fed a sulfur amino acid-deficient diet (0.25% L-methionine and no cysteine) supplemented with L-2-oxothiazolidine-4-carboxylate (0.35%) for 3 wk and compared with age-matched animals receiving the sulfur amino acid-deficient diet alone. Rats fed the sulfur amino acid-deficient diet had lower glutathione concentrations in bronchoalveolar lining fluid, lung, lymphocytes, and liver than rats fed a sulfur amino acid-deficient diet supplemented with L-2-oxothiazolidine-4-carboxylate. Rats fed the supplemented diet had normal tissue and bronchoalveolar lining fluid glutathione levels. Central venous plasma glutathione concentrations, mostly reflecting liver excretion, were less affected by L-2-oxothiazolidine-4-carboxylate supplementation. Rats fed L-2-oxothiazolidine-4-carboxylate supplementation had normal weight gain compared with a much lower weight gain in animals fed the sulfur amino acid-deficient diet alone. Thus, L-2-oxothiazolidine-4-carboxylate increased tissue glutathione concentrations and stimulated growth in rats. The lung glutathione status of the rats was reflected by glutathione concentrations in lymphocytes and the bronchoalveolar lining fluid, but not by the central venous plasma glutathione concentrations.

KEY WORDS: • glutathione • cysteine • rats • L-2-oxothiazolidine-4-carboxylate • sulfur amino acid deficiency

¹ JM acknowledges support from AGA AB Medical Research Fund and The Killough Trust. AJ had research support from Wyeth Laboratories. Partial support was provided by Clintec Technologies Inc.

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ To whom correspondence and reprint requests should be addressed. Current address: Department of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, 132 South 10th Street, Philadelphia, PA 19107-5244.

Manuscript received 9 March 1994. Revision accepted 26 September 1994.