ABSTRACT
BACKGROUND: Vincristine (VCR) is not a specific chemotherapeutic drug, responsible for cause several side effects. In this sense, many natural products have been studied to reduce this problem. Objetives: To examine the guarana neuroprotective effect in mice brain and cerebellum cells against vincristine (VCR) exposition. DESIGN: An in vitro study was performed using mice brain and cerebellum mice in monolayer culture. First, cells were exposed to VCR (0.009 µM for 24 hours and 0.0007 µM for 72 hours) to measure the cytotoxicity effect. Also, the cellular effect of hydroalcoholic extract of guarana (10; 30; 100 and 300 µg/mL) was evaluated in the same cells in 24 and 72 hours. After that, cells were exposed to VCR and guarana extract to evaluate the neuroprotective effect of guarana. MEASUREMENTS: Cell viability was analyzed by MTT, Free dsDNA and LHD Assays. Moreover, metabolism oxidative profile was evaluated by reactive oxygen species (ROS), lipoperoxidation (LPO) and catalase (CAT) levels through DCFH-DA, TBARS and Catalase Activity Assays, respectively. RESULTS: Our findings revealed that VCR caused neuronal cytotoxicity by reducing cell viability and increasing ROS and LPO levels. On the other hand, guarana did not cause cell damage in none of tested concentrations. In addition, guarana exhibited a notable protective effect on brain and cerebellum cells exposed to VCR by increasing cell viability, stimulating CAT activity, reducing levels of ROS and LPO. CONCLUSIONS: In this sense, guaraná is a remarkable antioxidant fruit that could be a target in new therapies development to reduce VCR neurotoxicity. .
Subject(s)
Antineoplastic Agents, Phytogenic/toxicity , Brain/drug effects , Cerebellum/drug effects , Neuroprotective Agents/administration & dosage , Paullinia , Plant Extracts/administration & dosage , Vincristine/toxicity , Animals , Antioxidants/administration & dosage , Brain/metabolism , Cell Survival/drug effects , Cells, Cultured , Cerebellum/metabolism , Male , Mice , Reactive Oxygen SpeciesABSTRACT
INTRODUCTION: Cisplatin is an effective chemotherapeutic agent commonly used in the treatment of malignant tumours, but ototoxicity is a significant side effect. OBJECTIVES: To discuss the mechanisms of cisplatin ototoxicity and subsequent cell death, and to present the results of experimental studies. MATERIAL AND METHODS: We conducted a systematic search for data published in national and international journals and books, using the Medline, SciELO, Bireme, LILACS and PubMed databases. RESULTS: The nicotinamide adenine dinucleotide phosphate oxidase 3 isoform (also termed NOX3) seems to be the main source of reactive oxygen species in the cochlea. These reactive oxygen species react with other molecules and trigger processes such as lipid peroxidation of the plasma membrane and increases in expression of the transient vanilloid receptor potential 1 ion channel. CONCLUSION: Cisplatin ototoxicity proceeds via the formation of reactive oxygen species in cochlear tissue, with apoptotic cell death as a consequence.
