Co-treatment with probucol does not improve lung pathology in hydroxypropyl-β-cyclodextrin-treated Npc1−/− mice
We previously reported the altered pulmonary function and pathology found in the mouse model of infantile Niemann-Pick C1 disease, the Npc1−/− mouse. Despite its salutary properties on brain and liver parameters, we did not find efficacious effects of hydroxypropyl-β-cyclodextrin (HPBCD) on pulmonary pathology. Since we had previously shown the beneficial effects of probucol on the somatic phenotype in the Npc1−/− mice, we have now studied the effects of combined therapy with HPBCD and probucol on the lung with mostly negative results. Body weight and lung weight for body weight were increased in parallel while inspiratory capacity for body weight was markedly decreased. Other physical, biochemical, and pulmonary function parameters were not much changed. There were trends towards improved lung elastance (p = 0.09) and compliance (p = 0.07).
KeywordsNiemann-pick C1 disease Mouse model Probucol Hydroxypropyl-β-cyclodextrin Pulmonary function Cholesterol storage
We thank Drs. Gordon A. Francis and Shinji Yokoyama, the University of Alberta, Canada for the gift of probucol and the Abitec Corp., Janesville, WI for the gift of Caprex 300.
RPE conceived, helped perform experiments, and wrote the manuscript; IAB performed experiments and analyzed data.
This work was supported by the National Institutes of Health [grant number 5RO1 ED000343-5, Theodore Trouard PI] and the Holsclaw Family Professorship of Human Genetics and Inherited Diseases (RPE).
Compliance with ethical standards
All mouse experiments were approved by our Institutional Review Board.
Conflict of interest
The authors declare that they have no conflict of interest.
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