Osteopontin does not mitigate cisplatin ototoxicity or nephrotoxicity in adult mice

Nicole Schmitt, Edwin W. Rubel

Research output: Contribution to journalArticle

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. Study Design. In vivo study using a model system of cisplatin toxicity in adult mice. Setting. Virginia Merrill Bloedel Hearing Research Center, University of Washington. Subjects and Methods. Osteopontin1/1 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 Osteopontin1/1 and Osteopontin+/+ mice. Cochlear and renal histologic damage following cisplatin appeared to be similar in Osteopontin1/1 and Osteopontin+/+ mice. Conclusion. 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.

Original languageEnglish (US)
Pages (from-to)614-620
Number of pages7
JournalOtolaryngology - Head and Neck Surgery
Volume149
Issue number4
DOIs
StatePublished - Oct 2013
Externally publishedYes

Fingerprint

Osteopontin
Cisplatin
Kidney
Inner Ear
Brain Stem Auditory Evoked Potentials
Cochlea
Outer Auditory Hair Cells
Creatinine
Histology
Cell Death
Poisons
Serum
Hearing
Regeneration
Immunohistochemistry
Wounds and Injuries

Keywords

  • chemotherapy
  • cisplatin
  • hearing loss
  • nephrotoxicity
  • ototoxicity

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Surgery

Cite this

Osteopontin does not mitigate cisplatin ototoxicity or nephrotoxicity in adult mice. / Schmitt, Nicole; Rubel, Edwin W.

In: Otolaryngology - Head and Neck Surgery, Vol. 149, No. 4, 10.2013, p. 614-620.

Research output: Contribution to journalArticle

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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. Study Design. In vivo study using a model system of cisplatin toxicity in adult mice. Setting. Virginia Merrill Bloedel Hearing Research Center, University of Washington. Subjects and Methods. Osteopontin1/1 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 Osteopontin1/1 and Osteopontin+/+ mice. Cochlear and renal histologic damage following cisplatin appeared to be similar in Osteopontin1/1 and Osteopontin+/+ mice. Conclusion. 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.",
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