Numerous techniques have been tested to attempt to prevent the onset or progression of age-related hearing loss (ARHL): raising the animals in an augmented acoustic environment (used successfully in mouse and rat models), enhancing the antioxidant defenses with exogenous antioxidant treatments (used with mixed results in mouse and rat models), raising the animals with a calorie restricted diet (used successfully in mouse and rat models), restoring lost endocochlear potential voltage with exogenous electrical stimulation (used successfully in the Mongolian gerbil model), and hypothetical enhancement of outer hair cell electromotility with salicylate therapy. Studies of human ARHL have revealed a set of unique hearing loss configurations with unique underlying pathologies. Animal research has developed models for the different forms of age-related peripheral pathology. Using the animal models, different techniques for prevention of ARHL have been developed and tested. The current review discusses ARHL patterns in humans and animal models, followed by discussions of the different prevention techniques.
Ototoxicity remains a major dose-limiting side effect of cisplatin. The current studies were carried out to evaluate the effectiveness of a novel Src-protein tyrosine kinase inhibitor in protecting the ear from cisplatin ototoxicity without compromising cisplatin's antitumor effects. The Src inhibitor has been shown to be effective in protecting the ear from noise-induced hearing loss. Three studies were carried out to determine whether this compound has otoprotective activity in rats treated with cisplatin. The first two studies used the Src inhibitor as a cotreatment with single doses of cisplatin in Fischer 344/NHsd rats and nude rats, respectively. Cochlear damage was assessed by auditory brainstem response threshold shifts and outer hair cell loss. The third study was carried out in nude rats with implanted HT-29 tumors, and the Src inhibitor was administered as a cotreatment with a lower dose of cisplatin. Cochlear damage and changes in tumor volume were assessed in the third study. In the first two studies, cotreatment with the Src inhibitor reduced cisplatin-induced hearing loss significantly. In the third study, little hearing loss was induced because of the use of a lower dose of cisplatin. However, cotreatment with the Src inhibitor did not exert a negative effect on cisplatin's slowing of tumor growth in the treated rats. The findings suggest that the Src inhibitor may provide an effective cotreatment with cisplatin to reduce cisplatin's ototoxicity, without compromising its antitumor capability.
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