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Study of the cytotoxicity and genotoxicity of the drug pregabalin in vitro models

Grant number: 13/09470-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2013
Effective date (End): June 30, 2014
Field of knowledge:Biological Sciences - Genetics - Mutagenesis
Principal researcher:Lusânia Maria Greggi Antunes
Grantee:Patrick Wellington da Silva dos Santos
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Anticonvulsants are primarily developed for treatment of epilepsy, however they showed efficiency in the treatment of disordes such as migraines, neuropathic pains, bipolar disorder and fibromyalgia. Pregabalin is one of the most important anticonvulsants and current leader of prescriptions. Pregabalin is structural analogue of gabapentin, which inhibits the calcium current through channels activated at high voltage. Currently, this drug is used to treat pain resulting from diabetic neuropathy, neuralgia postherpetic in adults and also cases involving chronic pain. Although mutagenicity studies of pregabalin resulted in absence of toxic effects, there are few results about its genotoxicity and use of human cell lines in the safety assessment. Moreover, pregabalin has been used for non-therapeutic purposes or recreational due to the pleasant effects experienced by some patients. This project proposes to conduct the MTT assay and the comet assay for assessment of cytotoxicity and genotoxicity, respectively. To achieve this, three different cell lines will be used: HepG2, L132 and PC12. HepG2 is a cell line isolated from a human hepatocellular carcinoma, which means that it has phase I and phase II enzymes, responsible for drugs metabolization; L132, a normal cell line from human embryonic lung, will be used to verify the specificity of the results; and PC12, rat pheochromocytoma, will be used because it represents a model for neurotoxicity and allows cell differentiation in neurons. Through the analysis of results, it will be possible to determine the safety of the drug tested in these three cell lines, contributing to a better understanding of pregabalin features and providing a conscious therapeutic use.