L-cysteine-induced brain damage in adult rats.
The time-dependent brain damage induced in adult rats by a single dose of L-cysteine was examined morphologically. Five-week-old male Sprague-Dawley rats that received 1500 mg/kg of L-cysteine by intraperitoneal injection were examined at 12 and 24 h and 3, 7, and 14 days after administration. Pathological changes were seen in the cerebral and cerebellar cortex. Neuronal karyopyknosis was observed in the granular and molecular layers of the superficial cerebellar cortex at 12 h, and well-demarcated infarct-like lesions were seen with a widespread distribution in the cerebral cortex at 24 h. A large number of lipid phagocytes and glial cell proliferation were noted in the affected regions on days 3 to 14. The neuronal cell death observed in the cerebellar granular layer cells was demonstrated to be due to apoptosis by histopathological and ultrastructural examinations as well as by the terminal deoxyribonucleotide transferase-mediated dUTP nick-end labeling (TUNEL) method and agarose gel electrophoresis for DNA laddering. It was found that L-cysteine induced brain lesions mainly in the cerebral and cerebellar cortex in adult rats, in contrast to lesions in various regions as observed in neonatal rats. The histopathological findings reported here suggest that the pathogenesis of the brain damage induced by L-cysteine in adult rats differs from that in neonatal rats. It appears likely that L-cysteine-induced brain damage is secondary to impairment of blood flow or other unknown factors that are responsible for the subsequent development of brain lesions.
Sawamoto
Osamu
O
Drug Safety and Metabolism, Otsuka Pharmaceutical Factory Inc, Muya-cho, Naruto, Tokushima 772-8601, Japan. sawamoos@otsukakj.co.jp
Hagiwara
Rika
R
Kurisu
Kazunobu
K
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D003545:Cysteine / Q000633:toxicity*; D053938:DNA Fragmentation; D020287:In Situ Nick-End Labeling; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D017207:Rats, Sprague-Dawley
D003545:Cysteine