In Vitro Impact of Macrolide Antibiotics on the Viability of Selected Mammalian Cell Lines
Keywords:
cell cultures, macrolides, mitochondrial activity, spiramycin, tilmicosin, tylosinAbstract
The aim of this study was to evaluate the in vitro cytotoxicity of different concentrations of macrolide antibiotics (tilmicosin-TILM, tylosin-TYL and spiramycin-SPI) on selected animal cell cultures. VERO cells (kidney cells from Macacus rhesus), FE cells (feline embryonal cells) and BHK 21 cells (cell line from young hamster kidneys) were used in the study and subjected to 50-1000 µg/mL macrolides, depending on the specific antibiotic and cell line. The cell viability was assessed using the metabolic mitochondrial MTT test. FE cells were the most sensitive to TILM with a significant decrease of viability at 100-150 µg/mL (P<0.001). VERO cells were the most resistant. FE cells showed the highest sensitivity to TYL, as 1000 µg/mL significantly reduced the cell viability (P<0.001) when compared to the untreated control. VERO cells exhibited the highest resilience, with no significant differences of viability in comparison to the control. BHK 21 cells exhibited the highest sensitivity to SPI, as all concentrations led to a significant decrease (P<0.001) of the viability. On the other hand, VERO cells revealed the highest resistance to SPI. Our data reveal that macrolides have a significant adverse effect on the cell viability.
References
Nikolaou, A., Meric, S., Fatta, D., Occurrence patterns of pharmaceuticals in water and wastewater environments. Analytical and Bioanalytical Chemistry, 2007, 387, 1225-1234.
Lai, H. T., Hou, J. H., Su, C. I., Chen, C. L., Effects of chloramphenicol, florfenicol, and thiamphenicol on growth of algae Chlorella pyrenoidosa, Isochrysis galbana, and Tetraselmis chui. Ecotoxicology and Environmental Safety, 2009, 72, 329-734.
Kümmerer, K., Antibiotics in the aquatic environment-a review-part II. Chemosphere, 2009, 75, 435-441.
Baran, W., Adamek, E., Ziemiańska, J., Sobczak, A., Effects of the presence of sulfonamides in the environment and their influence on human health. Journal of Hazardous Materials, 2011, 196, 1-15.
Giguere, S., Prescott, J.F., Baggot, J.D., Walker, R.D., Dowling, P.M., Antimicrobial Therapy in Veterinary Medicine, fourth ed., Wiley-Blackwell, New York, 2007, 626 p.
Hamilton-Miller, J. M., Chemistry and biology of the polyene macrolide antibiotics. Bacteriological Reviews, 1973, 37, 166-196.
Kanoh, S., Rubin, B. K., Mechanisms of action and clinical application of macrolides as immunomodulatory medications. Clinical Microbiology Reviews, 2010, 23, 590-615.
De Liguoro, M., Fioretto, B., Poltronieri, C., Gallina, G., The toxicity of sulfamethazine to Daphnia magna and its additivity to other veterinary sulfonamides and trimethoprim. Chemosphere, 2009, 75, 1519-1524.
Eguchi, K., Nagase, H., Ozawa, M., Endoh, Y. S., Goto, K., Hirata, K., Miyamoto, K., Yoshimura, H., Evaluation of antimicrobial agents for veterinary use in the ecotoxicity test using microalgae. Chemosphere, 2004, 57, 1733-1738.
Isidori, M., Lavorgna, M., Nardelli, A., Pascarella, L., Parrella, A., Toxic and genotoxic evaluation of six antibiotics on non-target organisms. Science of The Total Environment, 2005, 346, 87-98.
Lin, A.Y.C., Yu, T.H., Lin, C.F., Pharmaceutical contamination in residential, industrial, and agricultural waste streams: risk to aqueous environments in Taiwan, Chemosphere, 2008, 74, 131-141.
Tvrdá, E., Lukáč, N., Lukáčová, J., Jambor, T., Massányi, P., Dose- and time-dependent in vitro effects of divalent and trivalent iron on the activity of bovine spermatozoa. Biological Trace Element Research, 2015, 167, 36-47.
Shryock, T.R., Staples, J.M., DeRosa, D.C., Minimum inhibitory concentration breakpoints and disk diffusion inhibitory zone interpretive criteria for tilmicosin susceptibility testing against Pasteurella multocida and Actinobacillus pleuropneumoniae associated with porcine respiratory disease. Journal of Veterinary Diagnostic Investigation, 2000, 14, 389-395.
Ishida, Y., Abe, Y., Harabuchi, Y., Effects of macrolides on antigen presentation and cytokine production by dendritic cells and T lymphocytes. International Journal of Pediatric Otorhinolaryngology, 2007, 71, 397-405.
Viluksela, M., Vainio, P. J., Tuominen, R. K., Cytotoxicity of macrolide antibiotics in a cultured human liver cell line. Journal of Antimicrobial Chemothrapy, 1996, 38, 465-473.
Otoguro, K., Komiyama, K., Omura, S., Tyson, C.A., An in vitro cytotoxicity assay using rat hepatocytes and MTT and Coomassie blue dye as indicators. Alternatives to Laboratory Animals, 1991, 19, 352-360.
Jordan, W. H., The toxicity of tilmicosin given orally to rats for three months, R-09886. Lilly research Laboratories, Toxicological Division, 1989. Web page: http://www.inchem.org/documents/jecfa/jecmono/v38je06.htm.
Anderson, R. C., Harris, P. N., Lee, C. C., Maze, N., Small, R. M., Worth, H. M., The toxicology and pharmacology of tylosin, an antibiotic, and some salts of tylosin, X/E/4. Lilly research Laboratories, Toxicological Division, 1966. Web page: http://www.inchem.org/documents/jecfa/jecmono/v29je08.htm.
Baguer, A. J., Jensen, J., Krogh, P. H., Effects of the antibiotics oxytetracycline and tylosin on soil fauna. Chemosphere, 2000, 40, 751-757.
The European Agency for the Evaluation of Medicinal Products, Veterinary Medicines Evaluation Unit, 1994. Web page: http://www.ema.europa.eu/docs/en_GB/document_library/Maximum_Residue_Limits_-_Report/2009/11/WC500015984.pdf.
Havlík, J., Význam makrolidových antibiotik. Lékařské listy, 2008, 5, 7-9.