Hepatotoxic doses of copper sulfate induce metabolic memory in the redox system, which has an age-dependent nature

We tested the hypothesis that ageing is a consequence of the formation of metabolic memory and the possible role of the redox system as a basic, evolutionarily ancient system of metabolism regulation in stable metabolic patterns formation or metabolic states chronisation changed during adaptation. Three sequential intraperitoneal administration of copper sulfate to young (3-month-old Wistar rats) and old animals (20 months) at a dose of 1 mg/100 g of body weight (33% of the lethal dose) were used as adaptive inducers of the redox system. The amount of lipid hydroperoxides in mitochondria, cytosol in liver cells and blood serum, the activity of mitochondrial aconitate hydratase as an indicator of oxidative stress and the activity of a number of antioxidant enzymes were determined to assess the initial metabolic states, i. e. before exposure and 1, 30 and 60 days after exposure to copper sulfate on the body. It was shown that the amount of lipid hydroperoxides (LOOHs) in the liver mitochondria and blood serum of old rats before exposure to copper sulfate was more than 30% lower than in young animals, while the aconitase activity (an indicator of oxidative stress) was the same in animals of these ages. A lower amount of LOOHs coincided with an increased glutathione peroxidase activity in old animals. In old rats, the increased amount of LOOHs induced by copper ions was preserved even after eliminating copper from the body 30 days after administration. At the same time, it was restored to the original level in the young animals. The glutathione peroxidase and aconitase activity in mitochondria remained below the control values ​​​​even after the inducer elimination, and this was age-depending. The obtained results do not contradict the hypothesis of metabolic memory's role in ageing mechanisms. We postulate a relationship between the duration of maintenance of altered metabolic patterns and the polyfunctionality of enzymes and other metabolites.