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Evaluation of Genotoxicity and Mutagenicity of Ketamine on Human Peripheral Blood Leukocytes and in Salmonella typhimurium

2019; Elsevier BV; Volume: 62; Linguagem: Inglês

10.1016/j.tiv.2019.104718

1879-3177

Bruno C. Cavalcanti, João Batista de Andrade Neto, Antônio Adailson de Sousa Silva, Francisco Stefânio Barreto, José Roberto de Oliveira Ferreira, Cecília Rocha da Silva, Francisca Bruna Stefany Aires do Nascimento, Lívia Gurgel do Amaral Valente Sá, Hemerson Iury Ferreira Magalhães, Hélio Vitoriano Nobre Júnior, Manoel Odorico de Moraes,

Anesthesia and Sedative Agents

Ketamine is a potent uncompetitive NMDA receptor antagonist that provides amnesia, analgesia, environmental dissociation and immobility, where it has its cytotoxic effect well described in the literature. However, the work on its genotoxic/mutagenic potentials are scarce and insufficient and does not allow a reasonable evaluation of its role. Thus, in the present work, we decided to evaluate the genotoxic and mutagenic effects of ketamine on human peripheral blood leukocytes (PBLs) and Salmonella typhimurium (TA98, TA97a, TA100, and TA102) through several well-established experimental protocols based on different parameters in the presence or not of exogenous metabolizing S9 fraction. Our data revealed that ketamine induces a weak cytotoxic effect on human PBLs after 24 h and is devoided of hemolytic effects. A small amount of DNA strand breaks levels were detected in the modified comet assay (employment of FPG enzyme) only at highest concentrations (500 and 700 μg/mL) of ketamine, highlighting our pro-oxidant data regarding ketamine. However, the oxidative DNA lesions were almost completely repaired which reflects in the lack of mutagenesis (micronuclei and chromosomal aberrations) on human PBLs and no increases in revertants numbers on S. typhimurium/microsome test (500 to 5000 μg/plate). In summary, ketamine is a weak oxidative DNA damaging agent and is devoid of mutagenic properties on eukaryotic and prokaryotic models.