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Cysteine and Glycine Supplementation Modulate the Metabolic Response to Tumor Necrosis Factor in Rats Fed a Low Protein Diet

Institute of Human Nutrition, Southampton University, Southampton, SO9 3TU U.K. ^* Laboratoire des Proteines de la Reaction Inflammatoire, 75270 Paris Cedex 06, France

Responses to cytokines entail synthesis of substances rich in cysteine and glycine, such as glutathione (GSH), metallothionein and some plasma proteins. To examine the importance of an adequate supply of cysteine and glycine, we fed rats a low protein diet supplemented with L-cysteine and glycine, separately or in combination, or L-alanine, or a high protein diet for 1 wk before injection with tumor necrosis factor (TNF) or saline. The high protein diet-fed group had greater liver weight and zinc and GSH concentrations after TNF than the group fed the low protein diet supplemented with alanine. Glycine and cysteine supplementation resulted in greater liver weight after TNF treatment than did alanine supplementation. Cysteine supplementation had a similar influence on GSH concentration. Ceruloplasmin, -2-macroglobulin and -1-acid glycoprotein were higher in TNF-treated rats than in saline controls in each dietary group. However, feeding supplementary glycine and cysteine and the high protein diet often resulted in different values than seen in animals fed the low protein diet supplemented with alanine. Paradoxically, lower ceruloplasmin concentrations were observed in animals fed the former diets than in those fed the latter. -2-Macroglobulin concentration was lower in all animals fed low protein diets than in those fed the high protein diet. -1-Acid glycoprotein was lowest in groups fed cysteine-supplemented diets and highest in the glycine-supplemented group. A negative correlation (r = -0.538, P < 0.02) existed between hepatic GSH and serum ceruloplasmin concentrations in all rats given TNF, suggesting adaptations occur to maintain antioxidant defenses during inflammation when glutathione concentrations are influenced by the adequacy of the dietary intake of glycine and cysteine.

KEY WORDS: • tumor necrosis factor • rats • glycine • cysteine

¹ To whom correspondence and reprint requests should be addressed.

Manuscript received 30 January 1992. Revision accepted 22 June 1992.

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