The Effect of L-Carnitine on the Prevention of Experimentally Induced Cisplatin
نویسندگان
چکیده
Cisplatin is a platinum-containing compound which is widely used in the treatment of epithelial tumors. However this cytotoxic drug produces several adverse effects such as renal insufficiency, peripheral neuropathies and ototoxicity. Cisplatin induced ototoxicity is generally manifested as sensorineural hearing loss, which may be accompanied by tinnitus. The hearing loss is dose related, usually permanent, and typically bilateral and begins at higher frequencies, progressing to lower frequencies with continued treatment . The histological lesions in the cochlea after cisplatin administration are most prominent in the organ of Corti, and consist of degeneration and loss of the sensory cells. This loss typically starts at the first row of outer hair cells (OHCs) in the basal turn of the cochlea followed by the other OHC rows and, with increasing doses or prolonged administration, progresses towards the more apically located cochlear turns and eventually to the inner hair cells (IHCs). Free radical production with resulting glutation depletion and subsequent lipid peroxidation is a proposed mechanism for cisplatin ototoxicity. Several biochemical changes are linked to cochlear injury and OHC loss including an increase in free radicals or reactive oxygen species (ROS) . A change in the level of reduced glutathione and the activity of glutathione utilizing enzymes has been correlated with OHC loss due to cisplatin exposure. Endogenous antioxidant enzymes are important to the health and survival of OHCs such as superoxide dismutase and glutathione peroxidase .
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