After entering the cochlea, cisplatin is taken up into cells by diffusive and passive transport, copper transporter protein 1 (Ctr1) and organic cation transporter protein 2 (OCT2), endocytosis, and toxicity through DNA adduct formation, oxidative stress, mitochondrial dysfunction, inflammatory response, and ferroptosis ( 2.1 Cisplatin-induced DNA damage and apoptosis Once cisplatin enters the cell it can be hydrolyzed to form toxic aqua-cisplatin complexes and form intra-and interstrand crosslinks with DNA (Figure 1) FIGURE 1 2.2 Cisplatin induces oxidative stress The cochleas high metabolic rate results in its production of abundant reactive oxygen species (ROS), so it requires an active antioxidant defense system [glutathione (GSH), oxidized glutathione (GSSG), and antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR)] to achieve a dynamic oxidant-antioxidant balance to maintain healthy hearing
Frequency of anaemia in patients with systemic lupus erythematosus at tertiary care hospitals
Excess copper triggers the Fenton reaction, which induces mitochondrial lipid metabolism disorders
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For readers comparing options, it also helps to understand how dosing and protocols are structured in general, which our team outlines in our guide to how AOD 9604 dosing and cycles are typically approached under supervision
