Free radical scavenger depletion in post-ischemic reperfusion brain damage

Abstract

In the present study the influence of pretreatment with various GSH depletors such as buthionine sulfoximine (BSO) and diethylmaleate (DEM) was investigated in rats following cerebral post-ischemic reperfusion. Moreover, the effect of diethyldithiocarbamic acid (DDC), inhibitor of endogenous Cu,Zn-SOD, was evaluated. A significant depletion (40% of control value) of GSH levels was observed 24 h after DEM administration; after 48 h the value reached control levels. BSO showed maximal GSH depletion (59%) 24 h after administration and it was constant for almost 48 h. DDC administration caused a marked decrease (60%) of Cu,Zn-SOD activity 4 h after the injection and induced a marked decrease in percentage of survival with respect to control (untreated, ischemic) rats, when administered 4 h before ischemia. BSO and DEM prolonged the survival time of animals when administered 24 h before ischemia. This last paradoxical effect is unclear at present, but it might be due to an influence on glutamate cascade.

Plasma Antioxidant Activity as a Marker for a Favourable Outcome in Acute Ischemic Stroke

“…It was shown that concentration of GSH decreases early after ischemia (Cooper et al, 1980;Rehncrona et al, 1980) in rats, plasma concentration of protein thiols is associated with the degree of neurological impairment (Leinonen et al, 2000), ischemic outcome is worsened by pharmacological depletion of GSH (Vanella et al, 1993). Depletion of the total GSH and decrease of GSH/GSSG ratio are markers for oxidative stress in ischemic brain and as long as 72 h may be required to restore concentrations to normal values following an ischemic insult according to (Namba et al,2001;Park et al, 2000).…”

Oxidants, antioxidants and the ischemic brain

“…Depletion of total glutathione and a decreased GSH/GSSG ratio are markers for oxidative stress in ischemic brain and as long as 72·h may be required to restore concentrations to normal values following an ischemic insult (Namba et al, 2001;Park et al, 2000). Ischemic outcome is worsened by pharmacological depletion of glutathione (Vanella et al, 1993), but improved by administration of a glutathione mimetic, glutathione monoisopropyl ester, YM737 (Gotoh et al, 1994), or N-acetyl cysteine, a glutathione precursor. No study of glutathione reductase mutants in cerebral ischemia paradigms has been reported.…”

Disulfiram Augments Oxidative Stress in Rat Brain following Bilateral Carotid Artery Occlusion

“…The reduced efficiency of neurons in the ischemic brain to scavenge free radicals as a consequence of cerebral glutathione modulation and depletion of Cu-Zn SOD are possible key aspects leading to neurotoxic effects [30]. In fact, the neuronal injury caused by ischemia can be reduced by quenching the free radicals by enzymatic or nonenzymatic agents [10], pretreatment with vitamin E [33] and the administration of free-radical scavenging enzymes such as SOD and catalase [32].…”

“…Further, DSF is reduced to diethyldithiocarbamate (DDTC) nonenzymatically by GSH and enzymatically by GR [17]. DDTC has been shown to inhibit Cu-Zn superoxide dismutase and to deplete the free-radical scavenging capacity of the brain in ischemic rats [30].…”