Brain lipid peroxidation and antioxidant protectant mechanisms following acute cyanide intoxication.
The status of brain antioxidant enzymes and glutathione levels in mice intoxicated with KCN were correlated with lipid peroxidation in brain membranes. KCN (7 mg/kg, s.c.) rapidly increased conjugated dienes in brain lipids, with peak levels observed 30 min after cyanide treatment. At 60 min post cyanide, conjugated diene levels were only slightly elevated above controls. Temporal changes in activity of most antioxidant enzymes corresponded with the observed time course of cyanide-induced membrane lipid peroxidation. Thirty minutes after KCN, brain catalase (CA), glutathione peroxidase (GPX) and glutathione reductase (GR) activities were significantly reduced (percent inhibition compared to control: CA 44%, GPX 30%, and GR 41%). At 60 min, CA and GPX enzyme activity returned to control levels, whereas GR was elevated 34% above control activity. Superoxide dismutase was not significantly inhibited 30 min after KCN, but declined to 71% of control activity at 60 min. Brain levels of reduced glutathione declined 42% below control 30 min after cyanide and returned to within 9.4% of control at 60 min. At 30 and 60 min after cyanide, oxidize glutathione levels were not significantly changed from control levels. These studies suggest that membrane lipid peroxidation and subsequent membrane dysfunction observed in cyanide intoxication is related in part to a compromised antioxidant defense.
Ardelt
B K
BK
Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907.
Borowitz
J L
JL
Isom
G E
GE
D000818:Animals; D000975:Antioxidants / Q000096:biosynthesis; D001921:Brain / Q000378:metabolism*; D002374:Catalase / Q000037:antagonists & inhibitors; D002462:Cell Membrane / Q000378:metabolism; D003486:Cyanides / Q000506:poisoning*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors; D008054:Lipid Peroxides / Q000096:biosynthesis*; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D010084:Oxidation-Reduction; D011041:Poisoning / Q000201:enzymology / Q000378:metabolism; D011190:Potassium Cyanide / Q000506:poisoning*; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors
D000975:Antioxidants; D003486:Cyanides; D008054:Lipid Peroxides; D008563:Membrane Lipids; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione; D011190:Potassium Cyanide