PREVENTION OF CYANIDE-INDUCED CYTOTOXICITY BY NUTRIENTS IN ISOLATED RAT HEPATOCYTES

被引:47
作者
NIKNAHAD, H [1 ]
KHAN, S [1 ]
SOOD, C [1 ]
OBRIEN, PJ [1 ]
机构
[1] UNIV TORONTO,FAC PHARM,TORONTO M5S 2S2,ON,CANADA
关键词
D O I
10.1006/taap.1994.1207
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The effects of various glycolytic substrates and keto acid metabolites on the cytotoxic effects of cyanide have been studied with isolated rat hepatocytes. The sequence of cytotoxic events with 2 mM cyanide was an immediate inhibition of respiration followed by ATP depletion. Disruption of the plasma membrane occurred when 85-90% of ATP levels had been depleted. Fructose,dihydroxyacetone,glyceraldehyde toglutarate prevented cyanide-induced cytotoxicity and ATP depletion. Hepatocyte respiration was also restored by all except fructose. Fructose, unlike the others, also did not prevent cytotoxicity if added 30-60 min after cyanide. Fluoride, an inhibitor of the glycolytic enzyme enolase, prevented protection by fructose but not dihydroxyacetone or glyceraldehyde, suggesting that dihydroxyacetone and glyceraldehyde are cytoprotective by trapping cyanide, thereby restoring cytochrome oxidase activity and cellular ATP levels. Fructose, on the other hand, may be cytoprotective by supplying ATP through glycolysis. Hepatocytes isolated from fasted rats were five- to sevenfold more susceptible to cyanide-induced cytotoxicity. Furthermore, all glycogenic and gluconeogenic amino acids and carbohydrates were cytoprotective against cyanide toxicity toward fasted hepatocytes, suggesting that cellular energy stores determine their resistance to cyanide. (C) 1994 Academic Press, Inc.
引用
收藏
页码:271 / 279
页数:9
相关论文
共 37 条
[1]  
ALBAUM HG, 1946, J BIOL CHEM, V164, P45
[2]   CYANIDE TOXICITY IN HEPATOCYTES UNDER AEROBIC AND ANAEROBIC CONDITIONS [J].
AW, TY ;
JONES, DP .
AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 257 (03) :C435-C441
[3]   THE ANTIDOTAL ACTION OF SODIUM-NITRITE AND SODIUM THIOSULFATE AGAINST CYANIDE POISONING [J].
BASKIN, SI ;
HOROWITZ, AM ;
NEALLEY, EW .
JOURNAL OF CLINICAL PHARMACOLOGY, 1992, 32 (04) :368-375
[4]  
BAZOTTE RB, 1989, RES COMMUN CHEM PATH, V64, P193
[5]   ON THE MECHANISM OF HEPATIC GLYCOGENOLYSIS INDUCED BY ANOXIA OR CYANIDE [J].
BOLLEN, M ;
DERUYSSCHER, D ;
STALMANS, W .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1983, 115 (03) :1033-1039
[6]   LATE STEADY INCREASE IN CYTOSOLIC CA2+ PRECEDING HYPOXIC INJURY IN HEPATOCYTES [J].
BRECHT, M ;
BRECHT, C ;
DEGROOT, H .
BIOCHEMICAL JOURNAL, 1992, 283 :399-402
[7]   STATE OF OXIDATION-REDUCTION AND STATE OF BINDING IN CYTOSOLIC NADH-SYSTEM AS DISCLOSED BY EQUILIBRATION WITH EXTRACELLULAR LACTATE PYRUVATE IN HEMOGLOBIN-FREE PERFUSED RAT-LIVER [J].
BUCHER, T ;
BRAUSER, B ;
SIES, H ;
LANGGUTH, O ;
CONZE, A ;
KLEIN, F .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1972, 27 (02) :301-&
[8]  
CEDERBAUM AI, 1979, ARCH BIOCHEM BIOPHYS, V193, P551, DOI 10.1016/0003-9861(79)90062-6
[9]   TOXIC SMOKE INHALATION AND CYANIDE POISONING [J].
COHEN, MA ;
GUZZARDI, LJ .
AMERICAN JOURNAL OF EMERGENCY MEDICINE, 1988, 6 (02) :203-203
[10]   CYANIDE METABOLISM IN THE ISOLATED, PERFUSED, BLOODLESS HINDLIMBS OR LIVER OF THE RAT [J].
DEVLIN, DJ ;
SMITH, RP ;
THRON, CD .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1989, 98 (02) :338-349