Oxidative stress and antioxidant parameters in dogs with lymphoma during chemotherapy

Abstract

Purpose: Oxidative stress is a contributor in the development of neoplasms. OS is involved in multidrug resistance, adverse events, and outcome. Methods: Forty- two dogs with lymphoma have been included in the study, 30 of which were treated by Cyclophosphamide - Hydroxyldaunorubicin® (doxorubicin) - Oncovin® (vincristine) - Prednisolone (CHOP)-based protocol. Tumor samples were excised for histopatholgy, immunophenotyping, Ki67%, and biochemical analyses. Thiobarbituric acid reactive substances (TBARS), reduced and oxidized glutathione (GSH, GSSG), glutathione peroxidase (GSH-Px), Cu-Zn-superoxide dismutase (SOD), ferric reducing ability (FRAP), vitamin-C, -E, retinyl palmitate and trans-retinol in red blood cell hemolysates, lymph node homogenates, and blood plasma have been measured. The results were correlated with the outcome of the chemotherapy. Results: Median overall survival time (OST), relapse-free period (RFP) were 862 and 280 days, respectively, with adverse effects in 18 cases. Plasma GSH levels increased with age (dogs from 1 to 6 years vs 9 to 13 years, p = 0.0385). Lymph node FRAP levels were higher in samples with higher Ki67%, and plasma GSH/GSSG ratio was lower in dogs with increased OST and RFP. Plasma retinyl palmitate levels were lower in dogs with increased RFP. Overall survival time was increased with lower lymph node TBARS (cut off: 53 nmol/mg protein), GHS-Px (cut off: 16 U/mg protein), and higher plasma all-trans-retinol (cut off: 4 mg/ml). Relapse-free period was increased with lower lymph node TBARS (cut off: 53 nmol/mg protein), lower FRAP (cut off: 6 µmol/mg) and higher SOD (cut off: 70 U/mg protein). During chemotherapy a gradual increase in plasma vitamin E and C concentrations was detected, while GSH and GSSG showed a decrease before adverse events. Conclusion: Although oxidative stress parameters varied, some parameters, i.e. TBARS, GSH-Px, SOD, FRAP measured in lymph node samples, and plasma all-trans retinol might be used as prognostic indices.