Biochemical changes in the central nervous system of rats exposed to 1-bromopropane for seven days.
1-Bromopropane is used widely as an alternative to ozone-depleting solvents. The neurotoxic effects of this agent have been described in humans and experimental animals. Here we investigated the underlying mechanisms of the neurotoxic effects of 1-bromopropane by examining the initial biochemical changes in the central nervous system. Four groups of 9 Wistar male rats each were exposed to 200, 400, or 800 ppm 1-bromopropane or only fresh air, 8 h per day for 7 days. At the end of the experiment, the cerebrum, cerebellum, brain stem and lumbar enlargement of the spinal cord were dissected out from each rat (n = 8) for biochemical analyses. Morphological examinations of the nervous system were performed in the remaining rat of each group. 1-Bromopropane dose-dependently decreased neurospecific gamma-enolase, total glutathione, and nonprotein sulfhydryl groups in the cerebrum and cerebellum. Creatine kinase activity decreased dose-dependently in the brain and spinal cord. Histopathological examination showed swelling of preterminal axons in gracile nucleus and degeneration of myelin in peripheral nerves. Our results of low levels of gamma-enolase suggested that 1-bromopropane might primarily cause functional or cellular loss of neurons in the cerebrum and cerebellum. Glutathione depletion or modification to functional proteins containing a sulfhydryl base as a critical site might be the underlying mechanism of 1-bromopropane neurotoxicity.
Wang
Hailan
H
Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan. wanghl@med.nagoya-u.ac.jp
Ichihara
Gaku
G
Ito
Hidenori
H
Kato
Kanefusa
K
Kitoh
Junzoh
J
Yamada
Tetsuya
T
Yu
Xiaozhong
X
Tsuboi
Seiji
S
Moriyama
Yoshinori
Y
Sakatani
Rie
R
Shibata
Eiji
E
Kamijima
Michihiro
M
Itohara
Seiichiro
S
Takeuchi
Yasuhiro
Y
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D003402:Creatine Kinase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012997:Solvents / Q000633:toxicity*; D013047:Specific Pathogen-Free Organisms; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D013979:Tibial Nerve / Q000187:drug effects / Q000378:metabolism; D018675:Toxicity Tests
D006842:Hydrocarbons, Brominated; D012997:Solvents; D003402:Creatine Kinase; D010751:Phosphopyruvate Hydratase; D005978:Glutathione; C118559:1-bromopropane