Variations of hepatic antioxidant systems and DNA ploidy in rats aged 2 to 8 months

Abstract

Oxygen-reactive species are by-products of biological redox reactions and are involved in the development and aging processes. In order to test whether the time-dependent changes in the hepatic antioxidant defense are related to changes in DNA ploidy, we studied in rats, aged 2–8 months, the enzymes and metabolites related to the primary cell defense against oxidative stress, as well as the distribution of DNA into the cell cycle phases. Catalase and glutathione peroxidase, together with glutathione reductase and mitochondrial superoxide dismutase, underwent progressive and significant time course increases. Although no temporal changes were observed in the concentration of protein thiol groups and malondialdehyde in rats in the same age period, glutathione redox state, detected by the GSH/GSSG ratio decreased significantly to 41% ( P < 0.001) of the initial value. DNA content was assayed by flow cytometry in isolated hepatocytes, and changes in DNA ploidy and distribution in the cell cycle phases were determined. A sharp decrease in diploid population from rats aged 1–8 months (92.9% → 11.1%) and a pronounced increase in hepatocyte polyploid populations in the same age period (2.6% → 87.3%) were observed. However, liver cell population involved in S phase (DNA synthesis) was unchanged. These results indicate that the cell defense mechanisms against oxygen toxicity increased in liver of rats from 2–8 months in order to suppress the oxidative imbalance. During the 6-month period of a rat's life (2–8 months), the significant alterations of GSH/GSSG ratio to a more oxidative state have no influence on the proliferating capacity of the cells.