RESUMO
OBJECTIVE: The aim of this study was to analyse the genetic and non genetic risk factors for cisplatin ototoxicity. METHODS: This study was conducted on 72 children who received cisplatin based chemotherapy. Brock and Muenster classifications were used to evaluate ototoxicity seen in these children. 6 single nucleotide polymorphisms (SNP); ERCC1 rs 11615, GSTP1 rs1138272, GSTP1 rs1695, LRP2 rs 2075252, TPMT rs 12201199, COMT rs 9332377, were evaluated as genetic factors by real time PCR. Non genetic factors such as cranial irradiation, cumulative doses of cisplatin, age, gender, administration of other ototoxic drugs were analysed as well. By using Chi-square test, risk factors were matched with the ototoxicity classifications. Significant risk factors were reevaluated using logistic regression modelling. RESULTS: According to univariate analyses, male gender, co-treatment with aminoglycosides and mutant genotype of GSTP1 rs1695 were significantly related with cisplatin ototoxicity. Logistic regression modelling analyses also showed that male gender, co-treatment with aminoglycosides were found to be significantly related with cisplatin ototoxicity. Mutant genotype of GSTP1 rs1695 was not found to be significant, but close to the level of statistical significance. CONCLUSION: Male gender, co-treatment with aminoglycosides are significant risk factors for cisplatin ototoxicity in pediatric patients. Mutant genotype of GSTP1 rs1695 seems to be a genetic risk factor in univariate analyses, although not confirmed by multivariate analyses. Therefore, GSTP1 rs1695 SNP needs to be studied in larger series.
Assuntos
Aminoglicosídeos/efeitos adversos , Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Otopatias/induzido quimicamente , Otopatias/genética , Glutationa S-Transferase pi/genética , Adolescente , Fatores Etários , Antineoplásicos/administração & dosagem , Criança , Pré-Escolar , Cisplatino/administração & dosagem , Quimioterapia Combinada/efeitos adversos , Feminino , Genótipo , Humanos , Lactente , Masculino , Neoplasias/terapia , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Radioterapia/efeitos adversos , Fatores de Risco , Fatores SexuaisRESUMO
OBJECTIVES/HYPOTHESIS: Our objectives were to study effects of orally administered resveratrol (RV) against cisplatin (CDDP) ototoxicity in different doses and to investigate ultrastructural changes in the cochlea and brainstem. STUDY DESIGN: In vivo study using an animal model. METHODS: Thirty-two male Wistar albino rats were divided into six groups. Baseline distortion product otoacoustic emissions (DPOAEs) and auditory brainstem response (ABR) measurements were made. In groups I, II, and III, only saline, RV, and CDDP were given, respectively. Group IV, V, and VI animals were administered 10 mg/kg/day, 1 mg/kg/day, and 0.1 mg/kg/day of RV for 10 days, respectively, before 16 mg/kg CDDP injections were administered on day 11. All animals were sacrificed after repeated DPOAEs and ABR measurements were made on day 14. Cochleas of animals were investigated with transmission electron microscopy. Apoptosis were investigated with caspase-3 activity and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method in the brainstem. RESULTS: In groups IV and V, DPOAEs and ABR findings revealed that oral administration of RV 10 mg/kg/day and 1 mg/kg/day doses before CDDP injection enhanced ototoxicity. In group VI, electomicroscopy revealed better ultrastructural findings than in the cisplatin group; however, these changes were not reflected in the audiological findings accordingly. CONCLUSIONS: Our results implied that there were noticeable differences between different oral RV doses used for cisplatin ototoxicity. Especially in higher doses, RV was observed to enhance cisplatin ototoxicity.
