PROTECTOR EFFECT OF THE ANNATTO ON THE CISPLATIN-INDUCED MUTAGENICITY IN PC12 CELLS

BM12

Graciela Cristina dos Santos (1), Leonardo Meneghin Mendonça (2), Gilmara Ausech Antonucci (2), Lusânia Maria Greggi Antunes (2), Maria de Lourdes Pires Bianchi (2)

(1) Departamento de Alimentos e Nutrição - Faculdade de Ciências Farmacêuticas de Araraquara/UNESP. (2) Departamento de Análises Clínicas, Toxicológicas e Bromatológicas – Faculdade de Ciências Farmacêuticas de Ribeirão Preto/USP.

Cisplatin is one of the most potent and highly effective chemotherapeutic agents in treatment of several types of cancers. A major dose limiting side effect of this drug is neurotoxicity. About 20% of patients are unable to complete a full course of cisplatin therapy due to sensory neuropathy. Previous reports have demonstrated that this event can be mediated by oxidative stress as a result of generation of reactive oxygen species, and that the administration of antioxidants could be able to reduce the damage and protect the tissues. The annatto contains carotenoids with efficient antioxidant activity, and the present study was designed to investigate whether annatto has a protective effect against cisplatin-induced mutagenicity in PC12 cells. Thus, cultures were divided in groups for treatment: 1) a negative control, 2) cisplatin (0.1 μg/mL), 3) annatto pre-treatment (concentrations ranging from 0.2 to 1.0 μg/mL) with cisplatin (0.1 μg/mL). The analyzed parameters were cytotoxicity assessment by MTT method and mutagenicity by micronucleus test (MN) in PC12 binucleated cells. Cisplatin was not cytotoxic in the tested concentrations and annatto did not demonstrate expressive cytotoxicity, maintaining cell viability above 80% in all concentrations. We could identity that treatment with cisplatin 0.1 μg/ml induced more than 80 MN by 1000 BN cells, and that the pre-treatment with annatto was able to reduce MN induction more than 55%. Under the tested conditions we can say that cisplatin, in the concentration of 0.1 ug/mL was not cytotoxic, but was mutagenic in PC12 cells and that the annatto presented protective activity against this mutagenicity.