Genotoxic effect of non-lethal concentrations of minocycline in human glial cell culture

This study was financed in part by the Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior?Brazil (CAPES)?Finance Code 001 and supported by the Brazilian National Council for Scientific and Technological Development (CNPq). Federal University of Par?. Institute of Biological Science. Laboratory of Functional and Structural Biology. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Cultura Celular e Citogen?tica. Ananindeua, PA, Brasil. Federal University of Par?. Institute of Biological Science. Laboratory of Functional and Structural Biology. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Cultura Celular e Citogen?tica. Ananindeua, PA, Brasil. Federal University of Par?. Institute of Biological Science. Laboratory of Functional and Structural Biology. Bel?m, PA, Brazil. Federal University of Par?. Institute of Biological Science. Laboratory of Functional and Structural Biology. Bel?m, PA, Brazil. Federal University of Par?. Institute of Biological Science. Laboratory of Functional and Structural Biology. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Cultura Celular e Citogen?tica. Ananindeua, PA, Brasil. Federal University of Par?. Institute of Biological Sciences. Laboratory of Experimental Neuroprotection and Neuroregeneration. Bel?m, PA, Brazil. Federal University of Par?. Institute of Biological Science. Laboratory of Functional and Structural Biology. Bel?m, PA, Brazil. Minocycline has been proposed as a neuroprotective agent with pleiotropic effects on several experimental models of neurodegenerative diseases, including microglial inhibition. However, although most studies have focused on the central actions of minocycline in affecting microglial functions, other central nervous system (CNS) cell types may also be affected by this drug toxicity. Hence, considering that glial cells play a pivotal role on CNS physiology and are the main responsible for neuronal integrity, a comprehensive investigation on the effects of minocycline treatment on human glial cells is mandatory before translational studies to afford neuroprotection in humans. Therefore, we explored the cytotoxic and genotoxic effects of minocycline at different concentrations in glial cells using an in vitro model. To achieve this, U87 glial cell were exposed to 10?50 ?g/mL for 24 h. After exposure, cell viability, general metabolic status and genotoxic assays were performed. No changes were observed in cell viability, however, the general metabolic status decreased over 20 ?g/mL. In addition, although no chromossome aberrations were observed, evidences of genotoxicity, such as increase on micronucleus, buds and bridges, were observed from 10 ?g/mL. These results suggest that minocycline may induce genotoxic effects even at concentrations considered previously safe and should be used with caution in translational studies.