Long-term parenteral administration of 2-hydroxypropyl-β-cyclodextrin causes bone loss

Toxicologic Pathology
Ingrid Kantner, Reinhold G Erben

Abstract

Cyclodextrins are oligosaccharides which are used in the pharmaceutical industry and research as vehicles for application of apolar substances such as steroids. The aim of this study was to examine the long-term effects of parenteral administration of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) on bone. Sham-operated (SHAM) or ovariectomized (OVX) adult rats were subcutaneously injected with physiological saline, 50, or 200 mg/kg HP-β-CD daily. After 4 months, body weight in OVX rats and uterine weight in SHAM rats were significantly lower after administration of 200 mg/kg HP-β-CD, relative to vehicle controls. At 200 mg/kg, HP-β-CD was hepatotoxic as measured by increased serum transaminases, and reduced serum albumin. Moreover, 200 mg/kg HP-β-CD led to decreased vertebral and tibial bone mineral density (BMD), and to cortical thinning at the tibial shaft. Bone loss in HP-β-CD-treated rats was associated with increased bone resorption as measured by increased renal deoxypyridinoline excretion. Although 50 mg/kg HP-β-CD was devoid of overt signs of organ toxicity and did not impair BMD, bone resorption was already increased. In summary, subcutaneous long-term administration of HP-β-CD at a daily dose of 200 mg/kg led to increased ...Continue Reading

References

May 1, 1995·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·M E BellringerP Olivier
Feb 1, 1997·Journal of Pharmaceutical Sciences·T Irie, K Uekama
Jun 7, 2000·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·R G ErbenM Goldberg
Jun 26, 2001·Journal of Clinical Pharmacy and Therapeutics·L WillemsK de Beule
Jul 5, 2001·Biochemical and Biophysical Research Communications·L VandenputD Vanderschueren
Jul 12, 2002·Pflügers Archiv : European journal of physiology·Harriet S Tenenhouse, Yves Sabbagh
Oct 13, 2004·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Reinhold G ErbenBianca Breig
Jul 16, 2005·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Sarah Gould, Robert C Scott
May 18, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Nancy K MelloJack H Mendelson
Jan 18, 2008·Biomaterials·Xin-Ming LiuDong Wang
Mar 14, 2008·Toxicologic Pathology·Valentino J Stella, Quanren He
Apr 15, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Wen-Hong KanIrshad H Chaudry
Dec 31, 2008·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Bruno M LapauwJean-Marc Kaufman

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BETA
electrophoresis

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OsteoMeasure
SPSS

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