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Updated: May 9, 2026
Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity
Published on: March 16, 2018
Osteopontin does not mitigate cisplatin ototoxicity or nephrotoxicity in adult mice
Nicole C Schmitt1, Edwin W Rubel
1Virginia Merrill Bloedel Hearing Research Center, Seattle, Washington, USA.
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:
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.
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.
Insights
Osteopontin does not protect the inner ear or kidney from cisplatin toxicity in mice. This molecule is not essential for normal auditory or kidney function, though it may aid in kidney tubule cell regeneration after injury.
Area of Science:
- Ototoxicity and Nephrotoxicity Research
- Molecular Biology
- Biomedical Science
Background:
- Cisplatin is a widely used chemotherapeutic agent with significant ototoxic and nephrotoxic side effects.
- Osteopontin (OPN) is a pleiotropic protein involved in various biological processes, including cell survival and tissue repair.
- The potential role of osteopontin in mitigating cisplatin-induced organ damage remains largely unexplored.
Purpose of the Study:
- To investigate the role of osteopontin in protecting the inner ear and kidney from cisplatin-induced toxicity.
- To determine if osteopontin deficiency affects auditory function, cochlear integrity, renal function, or renal histology following cisplatin administration.
Main Methods:
- An in vivo study utilizing osteopontin-deficient (Osteopontin-/-) and wild-type (Osteopontin+/+) adult mice.
- Mice were treated with cisplatin (20 mg/kg) or saline, and assessed for ototoxicity (auditory brainstem response, cochlear histology) and nephrotoxicity (serum creatinine, renal histology).
- Osteopontin expression was examined via immunohistochemistry.
Main Results:
- No significant differences were observed in auditory brainstem response thresholds, outer hair cell death, or serum creatinine levels between osteopontin-deficient and wild-type mice after cisplatin treatment.
- Cochlear and renal histological damage following cisplatin exposure appeared similar in both groups of mice.
- A slight increase in renal osteopontin levels was noted 72 hours post-cisplatin treatment, but not in the inner ear.
Conclusions:
- Osteopontin is not essential for the development of normal auditory or renal function.
- Osteopontin does not appear to play a protective role against acute cisplatin-induced ototoxicity or nephrotoxicity.
- Elevated renal osteopontin following cisplatin injury may be implicated in the regeneration of proximal tubule cells.
