PMID- 8197590 OWN - NLM STAT- MEDLINE DCOM- 19940628 LR - 20190819 IS - 0300-483X (Print) IS - 0300-483X (Linking) VI - 89 IP - 2 DP - 1994 Apr 18 TI - Cyanide-induced lipid peroxidation in different organs: subcellular distribution and hydroperoxide generation in neuronal cells. PG - 127-37 AB - To evaluate hydroperoxide generation as a potential mechanism of cyanide neurotoxicity, mice were treated with KCN (7 mg/kg, subcutaneously (s.c.)) and the level of lipid peroxidation (expressed as conjugated dienes) was measured later in various organs. Brain showed elevated conjugated diene levels after cyanide but the liver, which is not considered a target for cyanide toxicity, showed no increase. The heart also showed no increase, whereas kidney conjugated dienes slowly increased to a peak 1 h after cyanide. In vitro studies show elevation of peroxidized lipids in mouse brain cortical slices following incubation with KCN (0.1 mM). Omission of calcium from the medium or pretreatment of brain slices with diltiazem (a calcium channel blocker) prevented formation of conjugated dienes by KCN. Calcium thus appears to play a critical role in cyanide-induced generation of peroxidized lipids in neuronal cells. Subcellular fractionation of brains from mice treated with cyanide showed that lipid peroxidation increased in the microsomal fraction but not in the mitochondrial fraction. Fluorescent studies using 2,7-dichlorofluorescein (a hydroperoxide sensitive fluorescent dye) show that hydroperoxides are generated rapidly after cyanide treatment of PC12 cells, a neuron-like cell, and hydroperoxide levels remain elevated for many minutes in the presence of cyanide. These results suggest that hydroperoxide generation with subsequent peroxidation of lipids may lead to changes in structure and function of certain membranes and contribute to the neurotoxic damage produced by cyanide. FAU - Ardelt, B K AU - Ardelt BK AD - Department of Pharmacology and Toxicology, Purdue University, West Lafayette, IN 47907-1334. FAU - Borowitz, J L AU - Borowitz JL FAU - Maduh, E U AU - Maduh EU FAU - Swain, S L AU - Swain SL FAU - Isom, G E AU - Isom GE LA - eng GR - ES04140/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - Ireland TA - Toxicology JT - Toxicology JID - 0361055 RN - BBX060AN9V (Hydrogen Peroxide) RN - EE92BBP03H (Diltiazem) RN - MQD255M2ZO (Potassium Cyanide) RN - SY7Q814VUP (Calcium) SB - IM MH - Analysis of Variance MH - Animals MH - Brain/*drug effects/metabolism/ultrastructure MH - Calcium/physiology MH - Cell Line MH - Diltiazem/pharmacology MH - Heart/drug effects MH - Hydrogen Peroxide/*metabolism MH - Injections, Subcutaneous MH - Kidney/drug effects/metabolism MH - Lipid Peroxidation/*drug effects/physiology MH - Liver/drug effects/metabolism MH - Male MH - Mice MH - Microsomes/drug effects/metabolism MH - Mitochondria/drug effects/metabolism MH - Neurons/*drug effects/metabolism/ultrastructure MH - Potassium Cyanide/*toxicity EDAT- 1994/04/18 00:00 MHDA- 1994/04/18 00:01 CRDT- 1994/04/18 00:00 PHST- 1994/04/18 00:00 [pubmed] PHST- 1994/04/18 00:01 [medline] PHST- 1994/04/18 00:00 [entrez] AID - 0300-483X(94)90221-6 [pii] AID - 10.1016/0300-483x(94)90221-6 [doi] PST - ppublish SO - Toxicology. 1994 Apr 18;89(2):127-37. doi: 10.1016/0300-483x(94)90221-6.