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Article

Glutathione Turnover Is Increased during the Acute Phase of Sepsis in Rats^{1 ,2}

Thierry Malmezat^*, Denis Breuillé, Pierre Capitan^*, Philippe Patureau Mirand^* and Christiane Obled^*3

^* Laboratoire d’Etude du Métabolisme Azoté, INRA, Clermont-Ferrand Theix, 63122 Saint Genès Champanelle, France, and Centre de Recherches Nestlé, Vers chez les blanc, Lausanne 26, Switzerland

³To whom correspondence should be addressed.

Glutathione metabolism during infection has been poorly documented. Glutathione concentrations and synthesis rates were studied in infected rats (2 d after infection) and in pair-fed controls. Glutathione synthesis rates were determined in liver, spleen, lung, small and large intestine, skeletal muscle, heart and blood by a 4-h or 6-h ¹⁵N cysteine infusion. The activities of four hepatic enzymes involved in glutathione metabolism were also determined. Glutathione synthesis rates were significantly greater in liver (+465%), spleen (+388%), large intestine (+109%), lung (+100%), muscle (+91%) and heart (+80%) of infected rats compared with pair-fed controls. Glutathione concentrations were also greater in these tissues but were unaffected in small intestine and lower in blood. In keeping with the stimulation of liver glutathione synthesis, the activities of liver -glutamyl-cysteine synthetase and glutathione reductase were significantly greater in liver of infected rats than of pair-fed rats. From the present study, we estimate that glutathione synthesis accounts for at least 40% of the enhanced cysteine utilization during infection. This increased utilization may be the primary cause of an enhanced cysteine requirement in infection.

KEY WORDS: • rats • glutathione synthesis rate • cysteine infusion • glutathione-related enzymes

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