Oxidative Damage as a Fundament of Systemic Toxicities Induced by Cisplatin-The Crucial Limitation or Potential Therapeutic Target?

Abstract

Cisplatin, an inorganic complex of platinum, is a chemotherapeutic drug that has been used for 45 years. Despite the progress of pharmaceutical sciences and medicine and the successful application of other platinum complexes for the same purpose, cisplatin is still the therapy of choice in many cancers. Treatment for testicular, ovarian, head and neck, urothelial, cervical, esophageal, breast, and pulmonary malignancies is still unthinkable without the use of this drug. However, cisplatin is also known for many side effects, of which the most pronounced are nephrotoxicity leading to acute renal failure, neurotoxicity, and ototoxicity. Mechanistic studies have proven that one of the conditions that plays a major role in the development of cisplatin-induced toxicities is oxidative stress. Knowing the fact that numerous antioxidants can be used to reduce oxidative stress, thereby reducing tissue lesions, organ failure, and apoptosis at the cellular level, many studies have defined antioxidants as a priority for investigation as a cotreatment. To investigate the mechanism of antioxidant action in vivo, many animal models have been employed. In the last few years, studies have mostly used rodents and zebrafish models. In this article, some of the most recent investigations that used animal models are listed, and the advantages and disadvantages of such experimental studies are pointed out.