title: Effects of sanguinarium, chlorhexidine and tetracycline on neutrophil viability and functions in vitro.
abstract: The effectiveness of an ideal antimicrobial agent depends on its ability to kill microbes with minimal toxicity to host cells. Depending on the treatment regimen, antimicrobial agents come into contact with host cells for various intervals of time. Sanguinarium (SANG), chlorhexidine (CHX) and tetracycline (TET) are 3 antimicrobial agents frequently used in the management of periodontal infections. However, their effects on host immune cells during different treatment regimens are not known. Due to their ability to serve as the first line of host defense against microbial infections, we have compared the effects of these antimicrobial agents on human neutrophil functions and viability. The results show that SANG is not lytic to neutrophils from peripheral blood or crevicular fluid, at all concentrations tested. However, exposures of neutrophils to very low concentrations of SANG (0.001%) inhibits neutrophil chemotaxis, oxidative metabolism and degranulation within 5 min. Increasing the exposure time results in a similar inhibition of neutrophil functions, albeit at 50-100 fold lower concentrations of SANG. CHX rapidly disrupts the cell membrane of both crevicular and peripheral blood neutrophils at concentrations above 0.005% within 5 min, and inhibition of all neutrophil functions is due to its lytic properties. While TET is least toxic to neutrophils, a dose dependent inhibition of neutrophil functions is dependent on the calcium concentrations of the cellular environment, and is observed only above 0.04% or higher concentrations in the absence of calcium. The data suggest that a critical cumulative concentration of these drugs is essential for their toxicity and inhibition of neutrophil functions. Therefore, both the length of exposure and the dose of the drug both are critical while considering the effectiveness of SANG, CHX or TET in the treatment of infections. Furthermore, due to differences in their mechanisms of action, the consequences of their effects on neutrophils may have significant bearing on tissue pathology as well as on their therapeutic efficacy.
authors.affiliation: Division of Oral Biology and Dental Surgical Sciences, University of Pittsburgh School of Dental Medicine, PA 15261, USA.
authors.forename: S
authors.initials: S
authors.lastname: Agarwal
authors.forename: N P
authors.initials: NP
authors.lastname: Piesco
authors.forename: D E
authors.initials: DE
authors.lastname: Peterson
authors.forename: J
authors.initials: J
authors.lastname: Charon
authors.forename: J B
authors.initials: JB
authors.lastname: Suzuki
authors.forename: K C
authors.initials: KC
authors.lastname: Godowski
authors.forename: G L
authors.initials: GL
authors.lastname: Southard
mesh_terms: D000328:Adult; D000470:Alkaloids / Q000633:toxicity*; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D000891:Anti-Infective Agents, Local / Q000633:toxicity*; D053119:Benzophenanthridines; D015550:Cell Degranulation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002710:Chlorhexidine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007546:Isoquinolines; D008826:Microbial Sensitivity Tests; D009504:Neutrophils / Q000187:drug effects*; D016897:Respiratory Burst / Q000187:drug effects; D013481:Superoxides / Q000037:antagonists & inhibitors; D013752:Tetracycline / Q000633:toxicity*
chemical_list: D000470:Alkaloids; D000900:Anti-Bacterial Agents; D000891:Anti-Infective Agents, Local; D053119:Benzophenanthridines; D007546:Isoquinolines; D013481:Superoxides; C005705:sanguinarine; D013752:Tetracycline; D002710:Chlorhexidine