Cystine feeding enhances defects of dietary copper deficiency by a mechanism not involving oxidative stress

Abstract

Dietary cystine supplementation exacerbates the effects of dietary copper deficiency. We examined the possibilities that this exacerbation is caused by an oxidative mechanism or by an effect on copper status. Male Sprague-Dawley rats (∼ 120 g) were fed copper-adequate or copper-deficient diets (0.5 or 16 mg/kg diet) that were supplemented with combinations of l-cystine (20 g/kg diet), vitamin E (37 mg/kg diet), and sodium tungstate (360 mg/L in drinking water). Dietary copper deficiency depressed serum and organ copper concentrations; increased heart size; caused anemia; reduced heart and liver superoxide dismutase and cytochrome c oxidase activities; and increased serum, heart, and liver thiobarbituric acid reactive substances. Cystine feeding exacerbated the cardiac enlargement and anemia of copper deficiency and reduced liver cytochrome oxidase and superoxide dismutase activities, but had no effect on organ copper content. Cystine feeding had no effect on serum or heart thiobarbituric acid reactive substances but depressed liver thiobarbituric acid reactive substances production. Neither vitamin E nor tungsten, which was used to inhibit sulfite oxidase and its potential production of free radicals, had an effect on the copper- or cystine-dependent changes in heart size, hematocrit, or hemoglobin. Dietary vitamin E and tungsten had variable beneficial effects on copper- and cystine-dependent changes in variables related to red blood cell size, but these effects could not be consistently related to the inhibition of TBARS production caused by vitamin E and tungsten. We conclude that, while cystine feeding enhanced signs of copper deficiency, it did not do so by an oxidative mechanism or by altering copper status.