Disulfiram augments oxidative stress in rat brain following bilateral carotid artery occlusion

Abstract

We examined the brain oxidative stress which accompanies 30 min of bilateral carotid artery ligation (BCAL) in terms of changes in brain levels of glutathione; reduced (GSH) and oxidized (GSSG) forms and the exacerbation of oxidative stress by disulfiram (DSF). These results indicate that BCAL alone decreases GSH content and limits glutathione reductase (GR) activity, and these changes were enhanced by DSF pretreatment. Similar observations were recorded with DSF alone. GR activity (74.3 +/- 4.0 micromol min(-1) mg(-1) tissue; p < 0.001) and GSH content (1.23 +/- 0.06 micromol min(-1) g(-1) tissue; p < 0.001) was attenuated in rats subjected to synergistic effect of BCAL and DSF with a concomitant increase of GSSG (0.006 +/- 0.006 micromol min(-1) g(-1) tissue; p < 0.001). Recovery of GSH/GSSG level and GR activity during reperfusion following 30 min BCAL was considerably delayed (96 h) in the BCAL and DSF group as compared to the recovery time of 24 h in the group subjected to BCAL-reperfusion alone. Perturbation of GSH/GSSG homeostasis as a result of BCAL was augmented by DSF. These findings clearly demonstrate central nervous system oxidative stress due to a BCAL-DSF synergistic effect. Based on the results obtained with this model, we conclude that DSF increases brain oxidative stress and this may be detrimental to alcoholics who might drink and develop an acetaldehyde-induced hypotension while taking DSF.

Increased Oxidative Dna Damage in Stroke‐prone Spontaneously Hypertensive Rats

“…Several studies have suggested that oxidative stress plays a role in ischaemia‐related brain damage 15 , 16 . Further observations regarding the occurrence of ischaemic stroke in SHRSP are of great interest because increased oxidative stress may directly affect brain damage in SHRSP.…”

Diethyldithiocarbamate complex with copper: the mechanism of action in cancer cells

“…Importantly, the studies report that dithiocarbamates per se have similar effects. Disulfiram was found to rapidly decrease GSH levels in vitro [53], and disulfiram administration in rat brains caused GSH decline with a concomitant increase in GSSH levels [54,55], formation of disulfiram-glutathione conjugates [56] and inhibition of GR activity [54,55]. PyDTC has shown an analogous impact on GSH content in vivo [57].…”