Lens thiol depletion by peroxynitrite. Protective effect of pyruvate

Pyruvate (PY) is known to be a potent scavenger of H2O2 by undergoing its peroxidative decarboxylation. While doing so, it also inhibits · OH generation, in addition to its direct · OH scavenging effect. We now hypothesize that PY would also be decarboxylated by cleaving the -O-O- bond in peroxynitrite (ONOO−) (PN), with the effect of protecting tissues against NOx induced damage. We have verified this by measuring 14CO2 formation on incubation of 1-14C-PY with 3-morpholinosydnonimine (SIN-1). Its protective effect against PN induced thiol depletion was initially assessed by determining its ability to inhibit oxidation of pure GSH. This was further evaluated by incubating lens homogenate with SIN-1 with or without PY. As conceived, PY did inhibit PN induced loss of protein as well as non-protein -SH. The findings therefore appear potentially useful to protect against nitrite induced damage to the lens and other tissues known to occur with aging and certain diseases such as diabetes.