Cisplatin and its derivatives are widely used chemotherapeutic drugs for cancer treatment. However, they have debilitating side effects in normal tissues and induce ototoxicity, neurotoxicity, and nephrotoxicity.
In kidneys, cisplatin preferentially accumulates in renal tubular cells causing tubular cell injury and death, resulting in acute kidney injury (AKI). Recent studies have suggested that DNA damage and the associated DNA damage response (DDR) are an important pathogenic mechanism of AKI following cisplatin treatment. Activation of DDR may lead to cell cycle arrest and DNA repair for cell survival or, in the presence of severe injury, kidney cell death. Modulation of DDR may provide novel renoprotective strategies for cancer patients undergoing cisplatin chemotherapy.
Archives of toxicology. 2015 Nov 13 [Epub ahead of print]
Shiyao Zhu, Navjotsingh Pabla, Chengyuan Tang, Liyu He, Zheng Dong
Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. , Departments of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA. , Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. , Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. , Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.