Open Access Moxidectin Toxicity in Senescence-Accelerated Prone and Resistant Mice

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Abstract:

Moxidectin has been used safely as an antiparasitic in many animal species, including for the eradication of the mouse fur mite, Mycoptes musculinus. Although no side effects of moxidectin have previously been reported to occur in mice, 2 strains of the senescence-accelerated mouse (SAMP8 and SAMR1) sustained considerable mortality after routine prophylactic treatment. To investigate the mechanism underlying this effect, moxidectin toxicosis in these mice was evaluated in a controlled study. Moxidectin was applied topically (0.015 mg), and drug concentrations in both brain and serum were analyzed by using HPLC coupled with mass spectrometry. The moxidectin concentration in brain of SAMP8 mice was 18 times that in controls, and that in brain of SAMR1 mice was 14 times higher than in controls, whereas serum moxidectin concentrations did not differ significantly among the 3 strains. Because deficiency of the blood–brain barrier protein P-glycoprotein leads to sensitivity to this class of drugs in other SAM mice, Pgp immunohistochemistry of brain sections from a subset of mice was performed to determine whether this commercially available analysis could predict sensitivity to this class of drug. The staining analysis showed no difference among the strains of mice, indicating that this test does not correlate with sensitivity. In addition, no gross or histologic evidence of organ toxicity was found in brain, liver, lung, or kidney. This report shows that topically applied moxidectin at a standard dose accumulates in the CNS causing toxicosis in both SAMP8 and SAMR1 mice.

Document Type: Research Article

Affiliations: 1: Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA. vlee@dar.emory.edu 2: California Animal Health and Food Safety Laboratory System, School of Veterinary Medicine, University of California, Davis, California 3: Department of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 4: Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 5: Division of Animal Resources, Department of Pathology and Laboratory Medicine, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia

Publication date: June 1, 2009

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  • Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.

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