Glutathione turnover is increased during the acute phase of sepsis in rats

Glutathione metabolism during infection has been poorly documented. Glutath ione 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 mus cle, heart and blood by a 4-h or 6-h N-15 cysteine infusion. The activities of four hepatic enzymes involved in glutathione metabolism were also deter mined. Glutathione synthesis rates were significantly greater in liver (+46 5%), spleen (+388%), large intestine (+109%), lung (+100%), muscle (+91%) a nd heart (+80%) of infected rats compared with pair-fed controls. Glutathio ne concentrations were also greater in these tissues but were unaffected in small intestine and lower in blood. In keeping with the stimulation of liv er glutathione synthesis, the activities of liver gamma-glutamyl-cysteine s ynthetase and glutathione reductase were significantly greater in liver of infected rats than of pair-fed rats. From the present study, we estimate th at glutathione synthesis accounts for at least 40% of the enhanced cysteine utilization during infection. This increased utilization may be the primar y cause of an enhanced cysteine requirement in infection.