Effects of high-dose cisplatin chemotherapy and conventional radiotherapy on urinary oxidative and nitrosative stress biomarkers in patients with head and neck

Cisplatin is a chemotherapeutic agent widely used in the treatment of several solid tumours. For patients with advanced head and neck squamous cell carcinoma in whom surgery is contraindicated, treatment with high-dose cisplatin administered every 21 days for 3 cycles concomitantly with conventional radiotherapy is recommended [1-3]. Its anticancer mechanism is mediated by DNA binding, which leads to the formation of inter-and intrastrand crosslinks and results in defective DNA templates, arrest of DNA synthesis and replication, DNA damage and, finally, cell death [4]. In addition, cisplatin accumulates in human cells (normal and tumour cells) resulting in enhanced production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which leads to mitochondrial damage and dysfunction [5,6]. In addition, there is a decrease in the antioxidant defence system mediated primarily by links formed between cisplatin and glutathione, which culminates in the depletion of glutathione [7]. The excessive generation of ROS and RNS damages biomolecules, resulting in lipid, protein and DNA/RNA oxidation and causing toxicities including nephrotoxicity, neurotoxicity, ototoxicity and hepatotoxicity [8-11]. The intensity of biomolecular damage can be determined by oxidative/nitrosative stress biomarkers. In this study, we used malondialdehyde (MDA) and lipid hydroperoxides, which are indicators of lipid peroxidation/oxidative stress biomarkers and nitrite, a nitrosative stress biomarker. Therefore, the aim of this study was to determine the effects of high-dose cisplatin chemotherapy and conventional radiotherapy on urinary levels of MDA, lipid hydroperoxides and nitrite biomarkers in patients with head and neck11818386CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPES