DOSE-DEPENDENT BRAIN-STEM NEUROPATHOLOGY FOLLOWING REPEATED ARTEETHERADMINISTRATION IN RATS

Histopathological effects of the artemisinin antimalarial, beta-arteet her, were evaluated in rats, Arteether (3.125-12.5 mg/kg/day, IM, in s esame oil) was administered for 7 consecutive days, Seven days followi ng the last injection, histological evaluation of the brainstem was pe rformed. Rats treated with 12,5 mg/kg showed significant neuropatholog y, including chromatolysis, in the nucleus trapezoideus and nucleus su perior olive, To a lesser extent, neuropathology was present in the nu cleus 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 o f these treatment conditions. These results confirm and extend previou s studies demonstrating brainstem neurotoxicity from artemisinin antim alarials. Furthermore, these results suggest that, in rats, brainstem auditory pathways may be particularly vulnerable. Early detection of a rteether neuropathology may, therefore, require examination of auditor y functions. Published 1998 Elsevier Science Inc.