Osteopontin Does Not Mitigate Cisplatin Ototoxicity or Nephrotoxicity in Adult Mice

Abstract

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. In vivo study using a model system of cisplatin toxicity in adult mice. Virginia Merrill Bloedel Hearing Research Center, University of Washington. 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. 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. 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.