Reactive oxygen species and cisplatin (ROS/CDDP)

Reactive oxygen species (ROS) and cisplatin represent a critical pharmacological relationship rather than a single therapeutic target. Cisplatin is a potent platinum-based chemotherapeutic agent that exerts its primary anti-tumor effect by forming DNA cross-links; however, its administration significantly elevates intracellular ROS levels, particularly within the mitochondria (Dasari & Tchounwou, 2014). This induction of oxidative stress plays a dual role: it enhances the apoptotic signaling required to kill cancer cells, but it is also the fundamental driver of cisplatin's severe systemic toxicities, including acute kidney injury and permanent hearing loss (Rybak et al., 2007; Miller et al., 2010). In healthy cells, cisplatin depletes antioxidant enzymes such as superoxide dismutase and catalase, leading to an accumulation of superoxide and hydroxyl radicals that damage cellular membranes and organelles. From a drug development perspective, this relationship is a major focus for the design of cytoprotective 'chemoprotectants' like amifostine, which aim to neutralize ROS in normal tissues without diminishing the drug's efficacy against the tumor. Understanding the balance between ROS-mediated cytotoxicity and ROS-induced side effects remains essential for optimizing platinum-based oncology regimens.

Other names

Cisplatin-induced oxidative stressROS-mediated cisplatin toxicityPlatinum-induced reactive oxygen species

Cisplatin induces the generation of reactive oxygen species (ROS) primarily through mitochondrial interference and the depletion of endogenous antioxidant defenses like glutathione. These ROS, including superoxide and hydroxyl radicals, cause oxidative damage to nuclear and mitochondrial DNA, proteins, and lipids, which synergizes with cisplatin-DNA adducts to trigger intrinsic apoptotic pathways (Dasari & Tchounwou, 2014; Miller et al., 2010).