title: Osteopontin does not mitigate cisplatin ototoxicity or nephrotoxicity in adult mice.
abstract: OBJECTIVE
  The goal of this study was to determine whether osteopontin, a molecule with a variety of biologic effects including cell death inhibition, plays an important role in protection of the inner ear and kidney from the toxic effects of the chemotherapeutic drug cisplatin.
  
  
  METHODS
  In vivo study using a model system of cisplatin toxicity in adult mice.
  
  
  METHODS
  Virginia Merrill Bloedel Hearing Research Center, University of Washington.
  
  
  METHODS
  Osteopontin+/+ and Osteopontin-/- adult mice were treated with intraperitoneal cisplatin (20 mg/kg) or saline (control). Osteopontin levels were investigated by immunohistochemistry. Auditory brainstem response thresholds and cochlear histology were used to assess ototoxicity, while serum creatinine and renal histology were used to assess nephrotoxicity. For quantitative experiments, 8 to 18 animals were included in each treatment group.
  
  
  RESULTS
  At 72 hours after cisplatin treatment, there was a slight increase in osteopontin levels within the kidney but not in the inner ear. There was no difference in auditory brainstem response threshold shifts, outer hair cell death, or serum creatinine between Osteopontin+/+ and Osteopontin-/- mice. Cochlear and renal histologic damage following cisplatin appeared to be similar in Osteopontin+/+ and Osteopontin-/- mice.
  
  
  CONCLUSIONS
  Osteopontin is not required for development of normal auditory or renal function. Osteopontin is unlikely to play a role in protection of the inner ear or kidney from acute cisplatin toxicity. Slight increases in renal osteopontin 72 hours after cisplatin injury may be important for regeneration of proximal tubule cells.
authors.affiliation: Virginia Merrill Bloedel Hearing Research Center, Seattle, Washington, USA.
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Schmitt
authors.forename: Edwin W
authors.initials: EW
authors.lastname: Rubel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000009:adverse effects* / Q000378:metabolism; D003051:Cochlea / Q000473:pathology; D003404:Creatinine / Q000097:blood; D007758:Ear, Inner / Q000187:drug effects*; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D006198:Hair Cells, Auditory / Q000166:cytology; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053495:Osteopontin / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D053495:Osteopontin; D003404:Creatinine; D002945:Cisplatin
keywords: chemotherapy; cisplatin; hearing loss; nephrotoxicity; ototoxicity