Possible relationship of polymerphosms in CYP2E1 gene with cisplatin-induced cell-oxidative stress in patients with head and neck cancer

• Grant number: 17/10187-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): August 01, 2017
• Effective date (End): November 30, 2019
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Patricia Moriel
• Grantee: Nadine de Godoy Torso
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated scholarship(s): 18/17654-7 - Potential impact of CYP2D6 genotyping on postoperative analgesia with tramadol in patients undergoing hip and knee arthroplasty, BE.EP.IC

Abstract

Head and neck cancer corresponds to tumors located in the upper aerodigestive tract. The most effective treatment consists of radiotherapy concomitant with chemotherapy with high doses of cisplatin, however, its use is limited due to its adverse reactions, mainly nephrotoxicity, caused by oxidative stress. The CYP450 enzyme complex is responsible for metabolising a wide variety of lipophilic compounds of an endogenous and exogenous nature. Studies suggest that the presence of the CYP2E1 subfamily, found in tissues such as the proximal renal tubule, predisposes an increased risk of developing nephrotoxicity compared to those that do not express this enzymatic subfamily. The objective of this study will be to verify a possible relation of the polymorphisms in the CYP2E1 gene with cisplatin induced cell oxidative stress in patients with head and neck cancer. We will include patients with head and neck cancer who will undergo antineoplastic treatment with cisplatin (80-100mg / m2 every 21 days for 3 cycles, being considered for the analysis only the 1st cycle) concomitant with radiation therapy. Cellular oxidative stress will be measured by the AmplexRed and MitoSox Red tests. The polymorphisms rs3813867, rs3813865, rs8192772 of CYP2E1 will be detected by Restriction Fragment Length Polymorphisms (PCR-RFLP). (AU)