CISPLATIN - AN OVERVIEW OF ITS EFFICIENCY AND TOXICITY

Cisplatin is the first heavy metal compound that has been found to possess antineoplastic activity. It effective in treating testicular, ovarian, head and neck, bladder, cervical, esophageal tumors, small cell lung carcinoma. Approximately 1% of cisplatin enters interacts with DNA, forming DNA-cisplatin bonds. Both apoptosis necrosis can be same population cells exposed cisplatin, mode death depends on concentration metabolic state target cell. In bloodstream, platinum component binds blood's proteins (hemoglobin, albumin transferrin), other significant portion glutathione cysteine-rich biomolecules. impairs mitochondrial antioxidant defense system (decreases GSH, NADPH levels, GCH/GSSG ratio, increases GSSG levels) leading oxidative stress. There are three main mechanisms resistance cisplatin: (1) enhanced repair cisplatin-induced DNA lesions, (2) decrease uptake and/or increase efflux (3) inactivation intracellularly. The usage limited due its toxicity side effects, which include neurotoxicity (numbness tingling, paresthesia, reduced deep tendon reflexes), nephrotoxicity (renal insufficiency, hypomagnesemia), ototoxicity (tinnitus bilateral high-frequency hearing loss), cardiotoxicity (changes electric heart activity, congestive failure), gastrotoxicity (nausea, vomiting, dyspepsia), etc. So far, there no effective, clinically administered, therapy for toxicity.