Reactive oxygen species and platelet-activating factor synthesis in age-related glomerulosclerosis

This work deals with the hypothesis that an increased synthesis of reactive oxygen species (ROS) or platelet-activating factor (PAF) (or both) may be implied in the genesis of age-related glomerulosclerosis. Plasma concentration and urinary excretion of both thiobarbituric acid-reactive substances (TBARS) and PAF were measured in young and old human beings and rats. Moreover, these same parameters as well as H2O2 synthesis and reduced glutathione (GSH) content were measured in isolated glomeruli of young (3 months) and old (18 months) Wistar rats. H2O2 synthesis and GSH content were also measured in cultured rat mesangial cells from young and old animals. Both human beings and rats showed a decreased glomerular filtration rate and an increased urinary protein excretion with respect to young individuals. Isolated glomeruli from old animals showed a higher protein content and a lower number of cell nuclei than those from young rats. No changes were detected in plasma concentration and urinary excretion of TBARS and PAF in either human beings or rats. Glomeruli from 18-month-old rats exhibited a higher content of TBARS and GSH and an increased synthesis of H2O2 and PAF than did those from 3-month-old rats. GSH content and H2O2 synthesis were higher in cultured cells from old rats than in those from young rats. These results point to the possibility that ROS or PAF could mediate some of the changes that characterize age-related glomerulosclerosis.