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Cisplatin

Decent Essays
CHAPTER 1
INTRODUCTION
Cisplatin is a platinum-based chemotherapeutic agent with proven efficacy against solid tumors. However, the clinical use of cisplatin is limited by the development of permanent hearing loss in cancer patients. There is currently no drug approved by the US Food and Drug Administration for cisplatin-induced hearing loss (1, 2). Multiple studies have shown that cisplatin profoundly damages outer hair cells (OHCs) present in the hook region, basal and middle turns of the cochlea (3, 4) with relative sparing of inner hair cells (IHCs) in these regions. Other regions of the cochlea such as the spiral ligament (SL), stria vascularis (SV) and spiral ganglion neuron (SGN) are also susceptible to cisplatin-induced damage (5-9).
The generation of reactive oxygen species (ROS) has long been recognized as an important contributor to cisplatin-induced hearing loss (10-14). Antioxidants have shown good promise initially for treating cisplatin-induced hearing loss. However, concerns have been raised that these agents could inhibit the anti-tumor action of cisplatin (15), reducing interest in developing anti-oxidants as otoprotectants. Recent studies have shown that cisplatin-induced ROS stimulate the activation of mitogen activated protein kinase (MAPK) pathway which in turn activates
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This agent is also a known inhibitor of STAT1 (21, 27) and shows beneficial effect in diseases such as diabetes, cancer, neurodegenerative disorders, cardiovascular disease and obesity (28-31). Our interest in EGCG stems from the fact that it could provide an orally effective STAT1 inhibitor with anticancer properties which could complement the overall therapeutic benefits of cisplatin. We show that oral EGCG is an effective otoprotective drug against cisplatin-induced hearing loss which did not alter its chemotherapeutic
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