Varied Protein Intake Alters Glutathione Metabolism in Rats

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Abstract
We tested the possibility that protein consumption greater than needed for optimum growth of young adult rats might increase either their hepatic glutathione (GSH) content or plasma GSH turnover. Additional aims were to characterize the relationship between hepatic GSH content and plasma turnover under physiologic conditions and to evaluate the ability of values obtained by noninvasive blood sampling to accurately predict hepatic GSH content. Male Sprague-Dawley rats (300 g) were adapted to purified diets containing 0, 5, 10, 20 or 40% casein. Plasma GSH and amino acid concentrations, hepatic GSH content and [35S]GSH-determined plasma GSH turnover were measured in the anesthetized, intact animals. As dietary protein increased from 0 to 20% casein, liver weight and liver GSH concentration (µmol/g wet wt) both increased. In rats fed the 40% casein diet, liver weight increased even further while liver GSH concentration decreased, with the net result that total liver GSH content of the 40% casein-fed group was not significantly different from that of the 20% casein-fed group. Plasma urea, cysteine, methionine and GSH concentrations increased with increasing protein intake, but with the exception of plasma urea, which increased by 60%, there was no further increase at the 40% casein level. Plasma GSH turnover also increased as dietary casein increased from 0 to 20% but was not significantly increased further by the 40% casein diet. A sigmoid function best described the relationship between plasma GSH turnover and hepatic GSH content (r = 0.80, P < 0.0001). The best indirect predictor of liver GSH content was not plasma GSH concentration (r = 0.56, P < 0.0001), but rather plasma cysteine (r = 0.84, P < 0.0001).