THE SAME CHEMICALS INDUCE DIFFERENT NEUROTOXICITY WHEN ADMINISTERED IN HIGH-DOSES FOR SHORT-TERM OF LOW-DOSES FOR LONG-TERM TO RATS AND DOGS

被引:34
作者
YOSHIMURA, S
IMAI, K
SAITOH, Y
YAMAGUCHI, H
OHTAKI, S
机构
[1] Department of Pathology, Hatano Research Institute, Food and Drug Safety Center, Kanagawa, 257, 729-5, Ochiai, Hadano
关键词
2,5-HEXANEDIONE; MISONIDAZOLE; CLIOQUINOL; ACRYLAMIDE; DOSE-RELATED DIFFERENTIAL NEUROTOXICITY; HIGH-DOSE NEUROTOXICITY; CEREBELLAR NUCLEI; RAT; BEAGLE DOG;
D O I
10.1007/BF03159961
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Dose- and term-dependent differences in the location and nature of brain lesions induced in rats and dogs by 2,5-hexanedione (2,5-HD), misonidazole, clioquinol, and acrylamide are reported. Subchronic neuropathies ("distal axonopathy") were induced by low-dose administration of these neurotoxicants and at high doses, lesions caused by acute or subacute neurotoxicity were found in the central nervous, system (CNS). In rats, 2,5-HD induced extracellular edema, nerve cell degeneration, and axonal degeneration in the cerebellar and vestibular nuclei. Similar lesions were observed in misonidazole-treated dogs and clioquinol induced nerve cell degeneration in the hippocampus and malacia in the piriform lobes of these animals. In rats, acrylamide induced degeneration of Purkinje cells. Although the mechanism(s) underlying the differential neurotoxicity of high and low doses of these neurotoxicants remains unclear, we suggest certain biochemical mechanisms, cytotoxic edema and excitotoxicity, as factors in the production of such lesions after high-dose treatment.
引用
收藏
页码:59 / 84
页数:26
相关论文
共 30 条
[2]   BEHAVIORAL AND ULTRASTRUCTURAL STUDIES OF DESMETHYLMISONIDAZOLE-INDUCED NEUROTOXICITY IN MICE [J].
CHAO, CF ;
SUBJECK, JR ;
JOHNSON, RJ .
BRITISH JOURNAL OF RADIOLOGY, 1983, 56 (661) :27-31
[3]  
GRIFFIN JW, 1979, NEUROTOXICOLOGY, V1, P299
[4]   NEUROPATHOLOGICAL ASPECTS OF BRAIN EDEMA [J].
KLATZO, I .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 1967, 26 (01) :1-&
[5]   PATHOPHYSIOLOGICAL ASPECTS OF BRAIN EDEMA [J].
KLATZO, I .
ACTA NEUROPATHOLOGICA, 1987, 72 (03) :236-239
[6]  
KRINKE G, 1978, ZBL VET MED A, V25, P277
[7]  
LANNEK B, 1974, ACTA VET SCAND, V15, P461
[8]  
LANNEK B, 1974, ACTA VET SCAND, V15, P219
[9]  
O'SHAUGHNESSY D J, 1986, Toxicologic Pathology, V14, P389
[10]  
Olney J.W., 1980, EXPT CLIN NEUROTOXIC, P272