DNA damage response in cisplatin-induced nephrotoxicity

Abstract

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) is 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.

53BP1 inhibits the migration and regulates the chemotherapy resistance of ovarian cancer cells

“…Cisplatin is commonly used by gynecologists to kill tumor cells by inducing DNA damage, promoting cell cycle arrest and increasing the rate of apoptosis (6,7). Previous studies have reported the following mechanisms underlying chemotherapy resistance: Certain tumor cells exhibit enhanced DNA repair functions and a weakened apoptotic process, with the transformation to epithelial stroma facilitating the secretion of matrix protein enzymes, including matrix metalloproteinase (MMP)-2 and MMP-9, which enable these tumor cells to break through the basement membrane, metastasize and invade.…”

DNA damage response in nephrotoxic and ischemic kidney injury

“…Clinically, the main cause of AKI includes ischemia/reperfusion injury, nephrotoxic damage, and sepsis (Basile et al, 2012; Togel and Westenfelder, 2014; Yang et al, 2016). Using various models of cisplatin-induced nephrotoxic AKI, we and others have delineated a rapid DDR in kidney cells and tissues(Zhu et al, 2015). Moreover, recent studies have begun to unveil DDR and its pathogenic role in renal ischemia/reperfusion injury.…”

Pharmacokinetic changes of cefdinir and cefditoren and its molecular mechanisms in acute kidney injury in rats

“…Nephrotoxicity could be observed in as many as 38% of patients after the treatment with cisplatin . It would affect the cycles of chemotherapy, and then diminishing the antitumour effect . The initiation and progression of kidney injury by cisplatin were multifactorial, including biotransformation, adduct formation, oxidative stress, inflammation and changes in cell cycle .…”