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• W1994735062 abstract "Hydroxypropyl-β-cyclodextrin (HPBCD) is an attractive drug candidate against Niemann-Pick Type C (NPC) disease. However, the safety of HPBCD treatment for NPC patients remains to be elucidated. In this study, we examined the acute toxicity of HPBCD in Npc1-deficient mice. When treated with HPBCD (20,000 mg/kg, subcutaneously), over half of the wild-type (Npc1+/+) or Npc1+/- mice died by 72 h after the injection. In contrast, all of the Npc1-/- mice survived. Marked pathophysiological changes, such as an elevation in serum transaminase and creatinine levels, hepatocellular necrosis, renal tubular damage, interstitial thickening, and hemorrhages in lungs, were induced by the HPBCD treatment in Npc1+/+ or Npc1+/- mice. However, these pathophysiological changes were significantly alleviated in Npc1-/- mice. In addition, in vitro analysis showed that the Npc1 gene deficiency and treatment with U18666A, an Npc1 inhibitor, remarkably attenuated the cytotoxicity of HPBCD in Chinese hamster ovary cells. These results suggest that the NPC1 genotype exacerbates the cytotoxicity of HPBCD and Npc1-/- mice have substantial resistance to the lethality and the organ injury induced by HPBCD injection compared with Npc1+/+ or Npc1+/- mice. We suggest that the Npc1 genotype should be considered in the safety evaluation of HPBCD using experimental animals and cells." @default.
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• W1994735062 date "2014-01-01" @default.
• W1994735062 modified "2023-10-01" @default.
• W1994735062 title "Influence of Npc1 genotype on the toxicity of hydroxypropyl-β-cyclodextrin, a potentially therapeutic agent, in Niemann–Pick Type C disease models" @default.
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• W1994735062 doi "https://doi.org/10.1016/j.ymgmr.2013.12.003" @default.
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