Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.18/521
Título: In vitro surfactant structure-toxicity relationships: implications for surfactant use in prophylaxis of sexually transmitted infections
Autor: Inácio, Ângela S
Mesquita, Katia A
Jordão, Luísa
Santos, Maria S
Moreno, António J M
Vaz, Winchil L C
Vieira, Otília V
Palavras-chave: Infecções Sexualmente Transmissíveis
Data: 19-Dez-2011
Citação: IX CNC Annual Meeting, 2011:13
Resumo: Sexually transmitted infections (STIs) are a major public-health problem worldwide. According to the World Health Organization there are 340 million new cases of bacterial and protozoal STIs (Gonorrhea, Syphilis, Chlamydia and Trichomoniasis) per year. The direct treatment costs and serious perinatal collateral damage caused by STIs represent hefty financial and social burdens, particularly in developing countries. Thus, the urgent need for woman-controlled, cheap, safe, effective, easy-to-use and easy-tostore topical applications for prophylaxis against STIs makes surfactant-containing formulations an interesting option that requires a more fundamental knowledge concerning surfactant toxicology and structure-activity relationships. We report in vitro effects of cationic surfactant concentration, exposure time and structure on the viability of mammalian cell types typically encountered in the vagina, namely, fully polarized and confluent epithelial cells, confluent non-polarized epithelial-like cells and dendritic cells. The microbicide effect of surfactants was also evaluated in Escherichia coli, used as Gram-negative bacteria cell model. Representatives of different types of commercially available cationic surfactants (CnTAB (n = 10 to 16), C12PB, and C12BZK) were examined in order to evaluate the effects of the hydrocarbon chain length and polar head group structure upon cell viability. All cationic surfactants were toxic at concentrations far below their critical micelle concentration (CMC) and showed significant differences in their toxicity towards polarized as compared with non-polarized cells. Cationic amphiphiles of the CnTAB family, differing in the length of their hydrophobic chain, exhibit a non-linear dependence of their toxicity on the number of carbons. Surfactants toxicity was also dependent on the chemical structure of the polar head group, being surfactants with larger polar head groups (C12BZK and C12PB) and more delocalized positive charge (C12PB) the most toxic. We also observed that surfactant concentrations close to the critical micelle concentration cause acute toxicity whereas lower concentrations can lead to a persistent post-exposure toxicity, suggesting an intracellular locus of action. This observation is supported by the results obtained for isolated rat liver mitochondria, showing that cationic surfactants decrease substrate generated mitochondrial membrane potential in a concentration-dependent manner and delayed the rebuilding of the potential by respiration after its collapse by ADP addition. Concerning surfactants microbicidal effect, bacteria were more susceptible to cationic surfactants and, contrary to mammalian cells, show biphasic dose-response toxicity curves, which may well imply different cellular targets. Altogether, our results pointed out to the fact that structure-activity relationships could be profitably exploited for STIs prophylaxis in vaginal gel formulations and contribute to a better understanding of the mechanisms involved in surfactant toxicity, have a predictive value with regard to their safety, and may be used to design more effective and less harmful surfactants for use in topical applications for STIs prophylaxis.
Peer review: yes
URI: http://hdl.handle.net/10400.18/521
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