EFFECT OF GLYCEROL-INDUCED ACUTE-RENAL-FAILURE ON GLUTATHIONE STATUS AND MITOGEN-INDUCED PROLIFERATION OF RAT SPLENOCYTES

The mitogen-induced activation responses of rat splenic lymphocytes we re determined for control and uremic rats. activation was quantified b y incorporation of [H-3]thymidine. Glycerol-induced acute renal failur e (ARF) inhibited the proliferation of both lipopolysaccharide (LPS)-i nduced B-lymphocytes and concanavalin A (Con A)-induced T-lymphocytes by 80% and 87%, respectively. The decrease in [H-3]thymidine incorpora tion in both the LPS- and con A-activated cells significantly correlat es with increases in plasma urea and creatinine concentrations (r = 0. 83). Total glutathione (GSH) concentration in the splenocytes was not significantly different in terms of GSH per 10(7) cell, although the overall GSH and the number of viable splenocytes were generally lower in the uremic rats. Determination of GSH- related enzymes (GSH S-trans ferase, GSSG reductase and GSH peroxidase) in the spleen of control ra ts and rats with ARF showed little difference in the activities of the se enzymes, although the GSSG/GSH ratio, which is an indication of oxi dative stress, was significantly increased in the spleen of uremic rat s. Incubation of normal splenocytes from control rats with uremic plas ma obtained from rats with ARF also significantly decreased the prolif eration responses. Metabolic inhibitors present in uremic plasma may c ontribute to the inhibitory action on mitogen-induced proliferation of B- and T- lymphocytes, although oxidative stress which occurs in ARF may itself be sufficient to affect the immune function.