The Effect of a Rat Diet Without Added Cu on Redox Status in Tissues and Epigenetic Changes in the Brain

The aim of the study was to determine whether feeding rats a diet without added Cu increases oxidation of macromolecules in tissues, as well as epigenetic changes in the brain. The rats were divided into two groups: the Cu-6.5 group which was fed a diet with a standard content of Cu in mineral mixture – 6.5 mg Cu from CuCO₃ per kg of diet; and the Cu-0 group which was fed a diet with a mineral mix without Cu supplementation. At the end of the experiment the rats were weighed and blood samples were collected. Finally, the rats were euthanized and then the liver, small intestine, spleen, kidneys, heart, brain, lung, testes and leg muscles were removed and weighed. In the blood of Cu-0 rats the lower Cp activity and greater GPx and CAT activity than in Cu-6.5 rats were noticed. In the liver, lungs, heart and testes of Cu-0 rats, a decreased content of Cu were noticed. Application of Cu-0 diets resulted in increased LOOH level in the small intestine, liver, and heart, as well as increased MDA content in the liver, spleen, lungs, brain and testes. The Cu-0 treatment caused a decrease in SOD activity in the heart, lungs and testes of the rats and a decrease in CAT activity in the small intestine. In the brain and testes of rats from the Cu-0 treatment, lower content of GSH + GSSG was observed. The brain of rats from the Cu-0 treatment showed an increase in the level of PCs, 8-OHdG, Casp 8 and DNA methylation. The research has shown that a deficiency of Cu in the diet impairs the body’s antioxidant defences, which in turn leads to increased lipid oxidation in the liver, small intestinal wall, heart, spleen, lungs, brain and testes, as well as to oxidation of proteins and DNA in the brain. A deficiency of Cu in the diet also increases methylation of cytosine in the brain.