Glutathione metabolism is modulated by postmortem interval, gender difference and agonal state in postmortem human brains.

The equilibrium between antioxidant function and oxidative stress is implicated in brain pathology. However, human studies on oxidant and antioxidant markers rely on postmortem tissue that might be affected by pre and postmortem factors. To evaluate the effect of these variables, we tested whether antioxidant enzymes [superoxide dismutase (SOD), catalase] glutathione (GSH) and related enzymes [gamma glutamylcysteine ligase (GCL), GSH peroxidase (GPx), GSH reductase (GR), GSH-S-transferase (GST)] and malondialdehyde (MDA, marker of lipid peroxidation) are affected in postmortem human brains (n=50) by increase in postmortem interval (2.5-26 h), gender difference and agonal state [based on Glasgow coma scale (GCS): range: 3-15] in different anatomical regions-frontal cortex (FC), cerebellum (CB) medulla oblongata (MO), substantia nigra (SN) and hippocampus (HC). While SOD and catalase activities were relatively unaltered, GR and GPx activities were affected by agonal state (GR in CB, p<0.05; GPx in MO, p<0.05) indicating altered GSH dynamics during the secondary events following neuronal injury. MO, SN and HC displayed low GSH compared to FC and CB. Total GSH level was decreased with PMI (MO, p=0.02) which could be partly attributed to increase in MDA levels with increasing PMI in MO (p<0.05). Total GSH level was higher in CB (p<0.017) and MO (p<0.04) in female brains compared to males. Interestingly, HC and SN regions showed significant stability in most of the markers tested. We suggest that while SOD and catalase were relatively unaffected by the pre and postmortem factors, GSH and its metabolic enzymes were significantly altered and this was more pronounced in MO of postmortem human brains. These data highlight the influence of pre and postmortem factors on GSH dynamics and the inherent differences in brain regions, with implications for studies on brain pathophysiology employing human samples.