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.
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.
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References
1. Rybak LP, Mukherjea D, Jajoo S, et al. Cisplatin ototoxicity and protection: clinical and experimental studies. Tohoku J Exp Med. 2009;219:177-186.
2. dos Santos NA, Carvalho Rodrigues MA, Martins NM, et al. Cisplatin-induced nephrotoxicity and targets of nephroprotection: an update. Arch Toxicol. 2012;86:1233-1250.
3. Chakraborty G, Jain S, Behera R, et al. The multifaceted roles of osteopontin in cell signaling, tumor progression and angiogenesis. Curr Mol Med. 2006;6:819-830.
4. Lund SA, Giachelli CM, Scatena M. The role of osteopontin in inflammatory processes. J Cell Commun Signal. 2009;3:311-322.
5. Weber GF, Lett GS, Haubein NC. Osteopontin is a marker for cancer aggressiveness and patient survival. Br J Cancer. 2010;103:861-869.
6. El-Tanani MK, Campbell FC, Kurisetty V, et al. The regulation and role of osteopontin in malignant transformation and cancer. Cytokine Growth Factor Rev. 2006;17:463-474.
7. Gu T, Ohashi R, Cui R, et al. Osteopontin is involved in the development of acquired chemo-resistance of cisplatin in small cell lung cancer. Lung Cancer. 2009;66:176-183.
8. Schmitt NC, Rubel EW, Nathanson NM. Cisplatin-induced hair cell death requires STAT1 and is attenuated by epigallocatechin gallate. J Neurosci. 2009;29:3843-3851.
9. Lopez CA, Olson ES, Adams JC, et al. Osteopontin expression detected in adult cochleae and inner ear fluids. Hear Res. 1995;85:210-222.
10. Sakagami M. Role of osteopontin in the rodent inner ear as revealed by in situ hybridization. Med Electron Microsc. 2000;33:3-10.
11. Zhao X, Jones SM, Thoreson WB, et al. Osteopontin is not critical for otoconia formation or balance function. JARO. 2008;9:191-201.
12. Iguchi S, Nishi S, Ikegame M, et al. Expression of osteopontin in cisplatin-induced tubular injury. Nephron Exp Nephrol. 2004;97:e96-e105.
13. Xie Y, Sakatsume M, Nishi S, et al. Expression, roles, receptors, and regulation of osteopontin in the kidney. Kidney Int. 2001;60:1645-1657.
14. Xie Y, Nishi S, Iguchi S, et al. Expression of osteopontin in gentamicin-induced acute tubular necrosis and its recovery process. Kidney Int. 2001;59:959-974.
15. Zhang B, Ramesh G, Norbury CC, et al. Cisplatin-induced nephrotoxicity is mediated by tumor necrosis factor-alpha produced by renal parenchymal cells. Kidney Int. 2007;72:37-44.
16. Poirrier AL, Van den Ackerveken P, Kim TS, et al. Ototoxic drugs: difference in sensitivity between mice and guinea pigs. Toxicol Lett. 2010;193:41-49.
17. Qureshy K, Blakley B, Alsaleh S, et al. End points for cisplatin ototoxicity. J Otolaryngol Head Neck Surg. 2011;40(suppl 1):S45-S48.
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Published In
Article first published online: July 24, 2013
Issue published: October 2013
Keywords
PubMed: 23884286
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This article was published in Otolaryngology–Head and Neck Surgery.
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