Effects of high-dose major components in oral disinfectants on the cell cycle and apoptosis in primary human gingival fibroblasts in vitro

Nomura, Yuji; Bhawal, Ujjal K.; Nishikiori, Ryo; Sawajiri, Masahiko; Maeda, Takeshi; Okazaki, Masanori

doi:10.4012/dmj.2009-031

Cited by 22 publications

(24 citation statements)

References 29 publications

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“…Such blocks were observed in some human corneal line cells treated with commercial anti-glaucoma medication containing BAK [9]. This observation has not been confirmed in vitro by others on corneal cells [18], primary gingival fibroblasts [2] or on lymphoid line cells in this study. Most likely, the G2M blocks observed in our previous publication were due to active compounds of ophthalmic medication and not due to BAK's influence, but studies on corneal epithelial cells still need to be performed.…”

Section: Discussion Discussion Discussion Discussioncontrasting

confidence: 39%

“…Due to chronicity and widespread use of such treatments, BAK's side effects are of great importance. BAK's toxicity, probably related to its pro-oxidative activities [2], is timeand dose-dependent. It also causes protein denaturation and disruption of the cytoplasmatic membranes [1].…”

Section: Introduction Introduction Introduction Introduction Introducmentioning

confidence: 99%

“…BAK, due to its antibacterial activities, is widely used especially in ophthalmology and dentistry. Its concentration in oral disinfectant mouthwash can reach as much as 10% [2] whereas in eye drops it varies between 0.004-0.05% [3]. Due to chronicity and widespread use of such treatments, BAK's side effects are of great importance.…”

Section: Introduction Introduction Introduction Introduction Introducmentioning

confidence: 99%

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Benzalkonium chloride (BAK) induces apoptosis or necrosis, but has no major influence on the cell cycle of Jurkat cells

Pożarowska¹,

Pożarowski²

2011

Folia Histochem Cytobiol.

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Section: Discussion Discussion Discussion Discussioncontrasting

confidence: 39%

Section: Introduction Introduction Introduction Introduction Introducmentioning

confidence: 99%

Section: Introduction Introduction Introduction Introduction Introducmentioning

confidence: 99%

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Benzalkonium chloride (BAK) induces apoptosis or necrosis, but has no major influence on the cell cycle of Jurkat cells

Pożarowska¹,

Pożarowski²

2011

Folia Histochem Cytobiol.

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“…Benzethonium, a cationic surfactant with bactericidal [1,2] and fungicidal [3] activity is widely used as preservative of vaccines and drugs [2,4], for topical 348 wound care [1] as well as for oral disinfection [5,6]. Recent evidence points to toxicity of benzethonium to human hematopoietic cells, Jurkat cells, neurons, glial cells, conjunctival cells and gingival fibroblasts [2,4,5,7].…”

Section: Introductionmentioning

confidence: 99%

Stimulation of Suicidal Erythrocyte Death by Benzethonium

Lang

Jilani²,

Zelenak³

et al. 2011

Cell Physiol Biochem

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Benzethonium, an antimicrobial surfactant widely used as preservative of pharmaceuticals, topical wound care product and oral disinfectant, triggers apoptosis of several cell types. The apoptosis is preceded and possibly triggered by mitochondrial depolarization. Even though lacking mitochondria, erythrocytes may similarly undergo suicidal cell death or eryptosis. Hallmarks of eryptosis include cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface. Eryptosis may be triggered by energy depletion, which leads to increase of cytosolic Ca²⁺-activity with subsequent Ca²⁺-sensitive cell shrinkage and cell membrane scrambling. Ca²⁺-sensitivity is enhanced by ceramide. The present study explored the effect of benzethonium on eryptosis. Cell membrane scrambling was estimated from binding of fluorescent annexin V to phosphatidylserine, cell volume from forward scatter in FACS analysis, cytosolic Ca²⁺-concentration from Fluo3-fluorescence, hemolysis from hemoglobin release, lactate formation by colorimetry and ceramide utilizing fluorescent antibodies. A 48 hours exposure to benzethonium (=5µM) significantly increased cytosolic Ca²⁺-concentration, decreased forward scatter and triggered annexin V-binding affecting some 30% of the erythrocytes at 5 µM benzethonium. Only 5% of treated erythrocytes were hemolytic. The effects of benzethonium on annexin V binding were blunted in the nominal absence of Ca²⁺ and in the presence of amiloride (1 mM) but not in the presence of the pancaspase inhibitor zVAD (10 µM). Benzethonium further significantly enhanced the effect of glucose depletion on cytosolic Ca²⁺-concentration and annexin V-binding, but significantly blunted the effect of glucose depletion on forward scatter. Benzethonium (5 µM) significantly enhanced lactic acid formation but not ceramide abundance. The present observations disclose a novel effect of benzethonium, i.e. triggering of suicidal death of erythrocytes.

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“…In Japan, CHX-containing mouthwash products must use maximum CHX concentrations of 0.0005-0.002%, whereas the effective concentration of CHX for management of halitosis is 0.05-0.2% (18,19). Like CHX, BZC is a cationic surfactant and its positively charged polar heads seem to play a role in its antimicrobial action (20). In Japan, BZC is one of the most widely used antiseptics for disinfection of the oral cavity and oropharyngeal regions (21), and this is the first report of its antiseptic efficacy for treatment of oral malodor.…”

Section: Figmentioning

confidence: 99%

Assessment of oral malodor and tonsillar microbiota after gargling with benzethonium chloride

Iwamura

Hayashi

Sato

et al. 2016

Journal of Oral Science

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The oropharyngeal area can be a source of halitosis. However, the relationship between healthy tonsillar microbiota and halitosis is poorly understood. We conducted a pilot clinical study to clarify the effect of gargling with an antiseptic agent on tonsillar microbiota in patients with halitosis. Twenty-nine halitosis patients who did not have otolaryngologic disease or periodontitis were assigned randomly to one of three groups: benzethonium chloride (BZC) gargle; placebo gargle; no gargle. Concentrations of volatile sulfur compounds (VSCs) in mouth air, the organoleptic score (ORS) and tongue-coating score (TCS) were measured before and after testing. IntroductionHalitosis is defined as an offensive and unpleasant breath odor. It is caused by various volatile molecules, including sulfur compounds, aromatic compounds, and short-chain fatty acids. Volatile sulfur compounds (VSCs) such as methyl mercaptan (CH 3 SH), hydrogen sulfide (H 2 S) and dimethyl sulfide (CH 3 SCH 3 ) are mainly responsible for halitosis (1). Most instances of halitosis can be attributed to oral causes. Usually, the source of malodor is flaking cells that have been sloughed off via turnover of epidermal cells and food residue attached to the posterior dorsum of the tongue, which are degraded by the proteolytic enzymes of anaerobic bacteria. These bacteria produce VSCs via enzymatic reactions with sulfur-containing amino acids (2).The ear-nose-throat (ENT) region is another site where halitosis can develop. Tonsillitis, sinusitis, and postnasal drip in the nasal cavity are frequent non-oral causes of

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Effects of high-dose major components in oral disinfectants on the cell cycle and apoptosis in primary human gingival fibroblasts in vitro

Cited by 22 publications

References 29 publications

Benzalkonium chloride (BAK) induces apoptosis or necrosis, but has no major influence on the cell cycle of Jurkat cells

Benzalkonium chloride (BAK) induces apoptosis or necrosis, but has no major influence on the cell cycle of Jurkat cells

Stimulation of Suicidal Erythrocyte Death by Benzethonium

Assessment of oral malodor and tonsillar microbiota after gargling with benzethonium chloride

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