BENZNIDAZOLE CAUSES OXIDATIVE STRESS IN BALB-C MICE-BEARING EHRLICH ASCITES TUMOR

Zeferino, R. C. (Universidade Federal de Santa Catarina), Mota, N. S. R. S. (Universidade Federal de Santa Catarina), Grinevicius, V. M. A. S. (Universidade Federal de Santa Catarina), Correia, J. F. G (Universidade Federal de Santa Catarina), Castro , L.

Universidade Federal de Santa CatarinaCancer stands out among the leading causes of mortality worldwide. Indeed, alternatives for patients under cancer treatment can rely on discovery of medicines including drug repositioning. These pharmaceutical approaching uses compounds with defined pharmacokinetic and pharmacodynamic properties applied in additional condition. In this sense, Benznidazole (BZN;PubChemCID31593) through its nucleophilic metabolites enable ROS (reactive oxygen species) generation and  oxidative stress induction triggers death of Chagas disease parasites. In same sense, increase of intracellular ROS in cancer cells arise as smart therapeutic target based in deficiency on redox capability of cancer cells.This study aim was to evaluate BZN-induced oxidative stress against Ehrlich ascites carcinoma (EAC, animal breast cancer model) in balb-c mice-bearing EAC (male, n=6, i.p.) treated during 9 days (PP00784, CEUA (Ethics Committee on the use of animals-UFSC (Federal University of Santa Catarina)). Treated groups received BZN (5 or 10 mg(milligram)/kg(kilogram)/day);saline (NaCl (Sodium chloride); 0,8%) with Dimethyl sulfoxide 1% (Negative Control – NC). In the end of treatment, ascitic liquid samples were collected for stress oxidative biomarker and antioxidant defense analysis (TBARS (Thiobarbituric acid reactive substances), SOD (Superoxide dismutase), CAT (Catalase), GPx (Gluthatione peroxidase) and GSH (Gluthatione)). Results showed increased lipid peroxidation around 15-fold comparatively to NC. SOD activity was increased around 9-fold comparatively to NC; CAT activity increased 261-fold after treatment with 5mg/kg/day and increased 179-fold with 10mg/kg/day comparatively to NC; GPx increased around 16-fold comparatively to NC. GSH content increased 48-fold after treatment with 5mg/kg/day and 25-fold fold with 10mg/kg/day of BZN. Therefore, BZN-enhanced oxidative stress in EAC cells showed potential to become a prototype molecule to research of new chemotherapy drug for a cancer treatment.   Benznidazole, oxidative stress, Ehrlich ascites carcinoma, Balb-c, breast-cancer