Dose-dependent brainstem neuropathology following repeated arteether administration in rats

被引:46
作者
Genovese, RF [1 ]
Newman, DB
Li, QG
Peggins, JO
Brewer, TG
机构
[1] Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Div Neurosci, Washington, DC 20307 USA
[2] Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Div Expt Therapeut, Washington, DC 20307 USA
[3] Uniformed Serv Univ Hlth Sci, Dept Anat & Cell Biol, Bethesda, MD 20814 USA
[4] Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand
关键词
antimalarial; arteether; artemisinin; neurotoxicity; rats;
D O I
10.1016/S0361-9230(97)00339-0
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Histopathological effects of the artemisinin antimalarial, beta-arteether, were evaluated in rats, Arteether (3.125-12.5 mg/kg/day, IM, in sesame oil) was administered for 7 consecutive days, Seven days following the last injection, histological evaluation of the brainstem was performed. Rats treated with 12,5 mg/kg showed significant neuropathology, including chromatolysis, in the nucleus trapezoideus and nucleus superior olive, To a lesser extent, neuropathology was present in the nucleus ruber, Mild neuropathology was also detected in other brainstem regions examined, Although no statistically significant neuropathology was found for the groups treated with 6.25 mg/kg/day and 3.125 mg/kg/day, substantial neuropathology was observed in a single rat in each of these treatment conditions. These results confirm and extend previous studies demonstrating brainstem neurotoxicity from artemisinin antimalarials. Furthermore, these results suggest that, in rats, brainstem auditory pathways may be particularly vulnerable. Early detection of arteether neuropathology may, therefore, require examination of auditory functions. Published 1998 Elsevier Science Inc.
引用
收藏
页码:199 / 202
页数:4
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