Impairment of respiratory functions in mitochondria of rats with an inherited hyperproduction of free radicals.

The functional characteristics of liver mitochondria and physical-chemical properties of mitochondrial membranes were studied in S rats with congenitally enhanced capacity to free radical generation in comparison to those in Wistar rats. It was shown previously that intense lipid peroxidation, numerous DNA rearrangements, protein oxidation, morbid states resembling human degenerative diseases and short life-span are characteristic of S rats. In present study we have demonstrated that in S rats at the age of 2-3 months the respiratory rate of the mitochondria in active metabolic state is lower than in Wistar rats, and so are the values for the respiratory control ratio, oxidative phosphorylation and membrane potential. By 10-12 months of age the decrease of the respiration rate and oxidative phosphorylation in S rat mitochondria become even more dramatic. These changes are associated with a decrease in the extent of dip of proteins into the membrane lipid layer or with the increase in the amount of protein aggregates. The results add to the understanding of the nature of morbid conditions developed under the effect of intensive free radical generation and to the comprehension of their role in aging.

Inherited enhancement of hydroxyl radical generation and lipid peroxidation in the S strain rats results in DNA rearrangements, degenerative diseases, and premature aging.

Previously by selection and inbreeding of Wistar rats susceptible or resistant to the cataractogenic effect of galactose the S and R rat strains differing in the intensity of hexose transport into the animal cells were developed. High level of OH-radical generation and enhanced lipid peroxidation are revealed in the liver and myocardium of the S rats in contrast to the R rats. Data are obtained supporting the view that enhanced generation of OH-radicals within the S rat tissues is due to oxidation and autooxidation of the abundant amounts of monosacharides intensely accumulating in the rat cells. In spite of continuous inbreeding for more than 40 generations and a high rate of homozygosity, numerous DNA rearrangements are revealed in the S rat genomes. Fragility of the S rat cell membranes is detected. Cataracts and other lens lesions, emphysema, tumors, cardiomyopathy-like changes in the myocardium, scoliosis, brain disfunctions are characteristic of the S rats, as well as low fertility and short life-span indicative of premature aging.