Amoebicidal effect of chlorine dioxide gas against pathogenic Naegleria fowleri and Acanthamoeba polyphaga.

The pathogenic free-living amoebae, Naegleria fowleri and Acanthamoeba polyphaga, are found in freshwater, soil, and unchlorinated or minimally chlorinated swimming pools. N. fowleri and A. polyphaga are becoming problematic as water leisure activities and drinking water are sources of infection. Chlorine dioxide (ClO2) gas is a potent disinfectant that is relatively harmless to humans at the concentration used for disinfection. In this study, we examined the amoebicidal effects of ClO2 gas on N. fowleri and A. polyphaga. These amoebae were exposed to ClO2 gas from a ready-to-use product (0.36 ppmv/h) for 12, 24, 36, and 48 h. Microscopic examination showed that the viability of N. fowleri and A. polyphaga was effectively inhibited by treatment with ClO2 gas in a time-dependent manner. The growth of N. fowleri and A. polyphaga exposed to ClO2 gas for 36 h was completely inhibited. In both cases, the mRNA levels of their respective actin genes were significantly reduced following treatment with ClO2 gas. ClO2 gas has an amoebicidal effect on N. fowleri and A. polyphaga. Therefore, ClO2 gas has been proposed as an effective agent for the prevention and control of pathogenic free-living amoeba contamination.

Oral mouthwashes for asymptomatic to mildly symptomatic adults with COVID-19 and salivary viral load: a randomized, placebo-controlled, open-label clinical trial.

BACKGROUND: Recent randomized clinical trials suggest that the effect of using cetylpyridinium chloride (CPC) mouthwashes on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in COVID-19 patients has been inconsistent. Additionally, no clinical study has investigated the effectiveness of on-demand aqueous chlorine dioxide mouthwash against COVID-19. METHODS: We performed a randomized, placebo-controlled, open-label clinical trial to assess for any effects of using mouthwash on the salivary SARS-CoV-2 viral load among asymptomatic to mildly symptomatic adult COVID-19-positive patients. Patients were randomized to receive either 20 mL of 0.05% CPC, 10 mL of 0.01% on-demand aqueous chlorine dioxide, or 20 mL of placebo mouthwash (purified water) in a 1:1:1 ratio. The primary endpoint was the cycle threshold (Ct) values employed for SARS-CoV-2 salivary viral load estimation. We used linear mixed-effects models to assess for any effect of the mouthwashes on SARS-CoV-2 salivary viral load. RESULTS: Of a total of 96 eligible participants enrolled from November 7, 2022, to January 19, 2023, 90 were accepted for the primary analysis. The use of 0.05% CPC mouthwash was not shown to be superior to placebo in change from baseline salivary Ct value at 30 min (difference vs. placebo, 0.640; 95% confidence interval [CI], -1.425 to 2.706; P = 0.543); 2 h (difference vs. placebo, 1.158; 95% CI, -0.797 to 3.112; P = 0.246); 4 h (difference vs. placebo, 1.283; 95% CI, -0.719 to 3.285; P = 0.209); 10 h (difference vs. placebo, 0.304; 95% CI, -1.777 to 2.385; P = 0.775); or 24 h (difference vs. placebo, 0.782; 95% CI, -1.195 to 2.759; P = 0.438). The use of 0.01% on-demand aqueous chlorine dioxide mouthwash was also not shown to be superior to placebo in change from baseline salivary Ct value at 30 min (difference vs. placebo, 0.905; 95% CI, -1.079 to 2.888; P = 0.371); 2 h (difference vs. placebo, 0.709; 95% CI, -1.275 to 2.693; P = 0.483); 4 h (difference vs. placebo, 0.220; 95% CI, -1.787 to 2.226; P = 0.830); 10 h (difference vs. placebo, 0.198; 95% CI, -1.901 to 2.296; P = 0.854); or 24 h (difference vs. placebo, 0.784; 95% CI, -1.236 to 2.804; P = 0.447). CONCLUSIONS: In asymptomatic to mildly symptomatic adults with COVID-19, compared to placebo, the use of 0.05% CPC and 0.01% on-demand aqueous chlorine dioxide mouthwash did not lead to a significant reduction in SARS-CoV-2 salivary viral load. Future studies of the efficacy of CPC and on-demand aqueous chlorine dioxide mouthwash on the viral viability of SARS-CoV-2 should be conducted using different specimen types and in multiple populations and settings.

Antimicrobial effects of chlorine dioxide in a hospital setting.

Chlorine dioxide is a powerful disinfectant with strong antibacterial properties. We conducted a study at different sites of the Lebanese American University Medical Center-Rizk Hospital to determine the efficacy of the ECOM air mask in decreasing the particle load. Air cultures were obtained from three different locations, namely the patients' elevator, visitors' elevator and mobile clinic and the number of colonies grown on each type of agar was determined. We also measured particle counts at the three sites both at baseline and after placement of the ECOM air mask. After 7 days of ECOM air mask use, the numbers of colonies grown on all types of media was decreased by 20-100% versus the baseline values. The counts of particles of different diameters (0.3, 0.5 and 5 µm) were decreased at all three sampled sites. This study highlighted the efficacy of the ECOM air mask. The utility of the gaseous form of ClO2 as an antiseptic in the hospital setting appears promising.

Antimicrobial efficacy of sodium hypochlorite and hyper-pure chlorine dioxide in the depth of dentin tubules in vitro.

OBJECTIVES: The study aimed to compare the antibacterial effect of a novel disinfectant, hyper-pure chlorine dioxide (hClO2) to sodium hypochlorite (NaOCl) in various depths of dentin tubules. MATERIALS AND METHODS: The distal root of the extracted lower molars was infected artificially with Enterococcus faecalis. The control group was rinsed with saline, and the test groups were irrigated with either 5% NaOCl or 0.12% hClO2. The longitudinally split teeth were stained by viability stain. The coronal third of the root was scanned with a confocal laser scanning microscope. The fluorescent intensities were measured, and the percentage of dead bacteria was calculated at depths up to 950 µm along the dentin tubules. The effect of penetration depth, irrigants, and their interaction on antimicrobial efficacy was determined by the linear mixed model. RESULTS: The percentage of dead bacteria was higher both in the NaOCl (45.1 ± 2.3%, p < 0.01) and in the hClO2 (44.6 ± 3.8%, p < 0.01) irrigant groups compared to saline (23 ± 4.5%); however, there was no difference between them. The percentage of killed bacteria was not correlated with the depths in any group (p = 0.633). CONCLUSIONS: Our results suggest that the functional penetration depth of NaOCl is at least 2-3 times more than published to date. There is no difference in disinfection effectiveness along the dentin tubules between NaOCl and hClO2 until at least the measured 950 µm. However, both were only able to eradicate the intratubular bacteria partially. CLINICAL RELEVANCE: Hyper-pure ClO2 could be used as an alternative or final adjuvant irrigant in endodontic treatment.

Antimicrobial efficiency of chlorine dioxide and its potential use as anti-SARS-CoV-2 agent: mechanisms of action and interactions with gut microbiota.

Chlorine dioxide (ClO2) is a disinfectant gas with strong antifungal, antibacterial, and antiviral activities. Applied on hard, non-porous surfaces as an aqueous solution or gas, the ClO2 exerts antimicrobial activity through its interaction and destabilization of cell membrane proteins, as well as through DNA/RNA oxidation, triggering cell death. As for viruses, the ClO2 promotes protein denaturalization mechanisms, preventing the union between the human cells and the viral envelope. Currently, ClO2 has been pointed out as a potential anti-SARS-CoV-2 clinical treatment for use in humans with the ability to oxidize the cysteine residues in the spike protein of SARS-CoV-2, inhibiting the subsequent binding with the Angiotensin-converting enzyme type 2 receptor, located in the alveolar cells. Orally administered ClO2 reaches the gut tract and exacerbates the symptoms of COVID-19, generating a dysbiosis with gut inflammation and diarrhea as side effects, and once absorbed, produces toxic effects including methemoglobinemia and hemoglobinuria, which can trigger respiratory diseases. These effects are dose-dependent and may not be entirely consistent between individuals since the gut microbiota composition is highly heterogeneous. However, to support the use of ClO2 as an anti-SARS-CoV-2 agent, further studies focused on its effectiveness and safety both in healthy and immunocompromised individuals, are needed.

Phthalate acid esters promoted the enrichment of chlorine dioxide-resistant bacteria and their functions related to human diseases in rural polyvinyl chloride distribution pipes.

Polyvinyl chloride (PVC) pipes are widely used as drinking water distribution pipes in rural areas of China. However, whether phthalate acid esters (PAEs) released from PVC pipes will affect tap water quality is still unknown. The influence of released PAEs on the water quality was analysed in this study, especially after ClO2 disinfection. The results indicated that ClO2 disinfection could control the growth of total coliforms and heterotrophic bacteria (HPC). However, when the ClO2 residual decreased to below 0.10 mg/L, HPC and opportunistic pathogens, including Mycobacterium avium and Pseudomonas aeruginosa, increased significantly. In addition, after ClO2 disinfection, PAEs concentrations increased from 10.6-22.2 µg/L to 21.2-58.8 µg/L in different sampling cites. Linear discriminant analysis (LDA) effect size (LEfSe) and statistical analysis of metagenomic profiles (Stamp) showed that ClO2 disinfection induced the enrichment of Pseudomonas, Bradyrhizobium, and Mycobacterium and functions related to human diseases, such as pathogenic Escherichia coli infection, shigellosis, Staphylococcus aureus infection, and Vibrio cholerae infection. The released PAEs not only promoted the growth of these ClO2-resistant bacterial genera but also enhanced their functions related to human diseases. Moreover, these PAEs also induced the enrichment of other bacterial genera, such as Blastomonas, Dechloromonas, and Kocuria, and their functions, such as chronic myeloid leukaemia, African trypanosomiasis, leishmaniasis, hepatitis C and human T-cell leukaemia virus 1 infection. The released PAEs enhanced the microbial risk of the drinking water. These results are meaningful for guaranteeing water quality in rural areas of China.

Evaluation of antimicrobial efficacies of chlorine dioxide gas released into the air towards pathogens present on the surfaces of inanimate objects.

The efficacy of ClO2 gas, as surface disinfectant at around 1,000 ppb against avian orthoavulaviruses type 1 (AOAV-1), infectious bronchitis virus (IBV), Escherichia coli (EC), and Salmonella Enteritidis (SE) was evaluated at the required level (≥99.9% reduction) on various surfaces. Exposing the surfaces to ClO2 gas for 1 hr reduced AOAV-1, except for rayon sheets which required 3 hr. However, 1 hr of exposure did not effectively reduced IBV titer. In the case of EC, glass plates and plastic carriers needed 1 hr of exposure, while rayon sheets required 2 hr. SE on rayon sheets required 1 hr exposure, but on the other tested surfaces showed inadequate reduction. Overall, ClO2 gas is an effective disinfectant for poultry farms.

Viral Disinfection of Porous Fomites Utilizing a Bacteriophage Model and Chlorine Dioxide Gas.

The pursuit of disinfecting porous materials or fomites to inactivate viral agents has special challenges. To address these challenges, a highly portable chlorine dioxide (ClO2) gas generation system was used to ascertain the ability of a gaseous preparation to inactivate a viral agent, the MS2 bacteriophage, when associated with potentially porous fomites of cloth, paper towel, and wood. The MS2 bacteriophage is increasingly used as a model to identify means of inactivating infectious viral agents of significance to humans. Studies showed that MS2 bacteriophage can be applied to and subsequently recovered from potential porous fomites such as cloth, paper towel, and wood. Paired with viral plaque assays, this provided a means for assessing the ability of gaseous ClO2 to inactivate bacteriophage associated with the porous materials. Notable results include 100% inactivation of 6 log bacteriophage after overnight exposure to 20 parts per million(ppm) ClO2. Reducing exposure time to 90 minutes and gas ppm to lower concentrations proved to remain effective in bacteriophage elimination in association with porous materials. Stepwise reduction in gas concentration from 76 ppm to 5 ppm consistently resulted in greater than 99.99% to 100% reduction of recoverable bacteriophage. This model suggests the potential of ClO2 gas deployment systems for use in the inactivation of viral agents associated with porous potential fomites. The ClO2 gas could prove especially helpful in disinfecting enclosed areas containing viral contaminated surfaces, rather than manually spraying and wiping them.

The effectiveness of chlorine dioxide gas in portable personal disinfectants to inhibit bacterial growth.

Disinfectants, especially air disinfectants, are necessary to prevent the potential spread of pathogens (bacteria and viruses) in the pandemic era and minimize the spread of pathogens. Some of the commercial disinfectant products that are often used generally contain chlorine dioxide (ClO2) gas. This study tested the effectiveness of two different commercial disinfectants, a liquid stick disinfectant and a powder disinfection card, to carry out the disinfection of pathogenic bacteria in the environment. These two disinfectants were used as a medium for releasing chlorine dioxide gas which has a much stronger bactericidal effect. In the form of liquid stick, ClO2 is more effective in the disinfection process rather than in the form of powder. The effectiveness of the liquid disinfectant in inhibiting the growth of pathogenic bacteria is influenced by the temperature and the area of the open space covered. Considering that the release from both disinfectants used is very small (0.002 ppmv/h), it takes a small area to ensure that the disinfection process runs effectively.

Lipid Oxidation and Volatile Compounds of Almonds as Affected by Gaseous Chlorine Dioxide Treatment to Reduce Salmonella Populations.

The effects of gaseous chlorine dioxide (ClO2) treatment, applied to inactivate Salmonella, on lipid oxidation, volatile compounds, and chlorate levels of dehulled almonds were evaluated during a 3 month accelerated storage at 39 °C. At treatment levels that yielded a 2.91 log reduction of Salmonella, ClO2 promoted lipid oxidation as indicated by increased peroxide values, total acid number, conjugated dienes, and thiobarbituric acid-reactive substances. Furthermore, several chlorine-containing volatile compounds including trichloromethane, 1-chloro-2-propanol, 1,1,1-trichloro-2-propanol, and 1,3-dichloro-2-propanol were identified in ClO2-treated samples. However, all the volatile chlorine-containing compounds decreased during the 3 months of storage. Chlorate (26.4 ± 5.1 µg/g) was found on the ClO2-treated samples. The amounts of non-ethanol alcohols, aldehydes, and carboxylic acids increased following ClO2 treatments. Some volatiles such as 2,3-butanediol that were present in non-treated samples became non-detectable during post-ClO2 treatment storage. Overall, our results demonstrated that gaseous ClO2 treatment promoted lipid oxidation, generation of volatiles of lipid origin, and several chlorine-containing compounds.

Metabolome analysis shows that ultrasound enhances the lethality of chlorine dioxide against Salmonella Typhimurium by disrupting its material and energy metabolism.

The physiological status of Salmonella after its ultrasonication was investigated to reveal the potential mechanism through which ultrasound enhances the lethality of chlorine dioxide against Salmonella. Applying either the probe ultrasound (US) or water bath ultrasound (WUS) disrupted the cellular structure of Salmonella bacteria, increased the permeability of their bacterial outer membrane (US: 9.00 %, WUS: 11.96 %), and caused intracellular reactive oxygen species to accumulate (US: 13.95 %, WUS: 4.34 %,), which resulted in a reduction of ATP (US: 15.22 %, WUS: 14.15 %) and ATPase activity (US: 3.13 %, WUS: 26.06 %). This series of adverse effects eventually led to the disruption of the metabolic process in Salmonella cells, by mainly altering the metabolism of lipids, small molecules, and energy. Therefore, ultrasound enhances the lethality of chlorine dioxide primarily by disrupting the cellular structure, intracellular material, and energy homeostasis of Salmonella. This finding will promote the development and application of ultrasonic-assisted sterilization technology in food industries.

Can nasal irrigation with chlorine dioxide be considered as a potential alternative therapy for respiratory infectious diseases? The example of COVID-19.

Chlorine dioxide (ClO2) is a high-level disinfectant that is safe and widely used for sterilization. Due to the limitations on preparing a stable solution, direct use of ClO2 in the human body is limited. Nasal irrigation is an alternative therapy used to treat respiratory infectious diseases. This study briefly summarizes the available evidence regarding the safety/efficacy of directly using ClO2 on the human body as well as the approach of nasal irrigation to treat COVID-19. Based on the available information, as well as a preliminary experiment that comprehensively evaluated the efficacy and safety of ClO2, 25-50 ppm was deemed to be an appropriate concentration of ClO2 for nasal irrigation to treat COVID-19. This finding requires further verification. Nasal irrigation with ClO2 can be considered as a potential alternative therapy to treat respiratory infectious diseases, and COVID-19 in particular.

Effects of the Preferential Oxidation of Phenolic Lignin Using Chlorine Dioxide on Pulp Bleaching Efficiency.

Chlorine dioxide is widely used for pulp bleaching because of its high delignification selectivity. However, efficient and clean chlorine dioxide bleaching is limited by the complexity of the lignin structure. Herein, the oxidation reactions of phenolic (vanillyl alcohol) and non-phenolic (veratryl alcohol) lignin model species were modulated using chlorine dioxide. The effects of chlorine dioxide concentration, reaction temperature, and reaction time on the consumption rate of the model species were also investigated. The optimal consumption rate for the phenolic species was obtained at a chlorine dioxide concentration of 30 mmol·L-1, a reaction temperature of 40 °C, and a reaction time of 10 min, resulting in the consumption of 96.3% of vanillyl alcohol. Its consumption remained essentially unchanged compared with that of traditional chlorine dioxide oxidation. However, the consumption rate of veratryl alcohol was significantly reduced from 78.0% to 17.3%. Additionally, the production of chlorobenzene via the chlorine dioxide oxidation of veratryl alcohol was inhibited. The structural changes in lignin before and after different treatments were analyzed. The overall structure of lignin remained stable during the optimization of the chlorine dioxide oxidation treatment. The signal intensities of several phenolic units were reduced. The effects of the selective oxidation of lignin by chlorine dioxide on the pulp properties were analyzed. Pulp viscosity significantly increased owing to the preferential oxidation of phenolic lignin by chlorine dioxide. The pollution load of bleached effluent was considerably reduced at similar pulp brightness levels. This study provides a new approach to chlorine dioxide bleaching. An efficient and clean bleaching process of the pulp was developed.

Imaging and plate counting to quantify the effect of an antimicrobial: A case study of a photo-activated chlorine dioxide treatment.

AIM: To assess removal versus kill efficacies of antimicrobial treatments against thick biofilms with statistical confidence. METHODS AND RESULTS: A photo-activated chlorine dioxide treatment (Photo ClO2 ) was tested in two independent experiments against thick (>100 µm) Pseudomonas aeruginosa biofilms. Kill efficacy was assessed by viable plate counts. Removal efficacy was assessed by 3D confocal scanning laser microscope imaging (CSLM). Biovolumes were calculated using an image analysis approach that models the penetration limitation of the laser into thick biofilms using Beer's Law. Error bars are provided that account for the spatial correlation of the biofilm's surface. The responsiveness of the biovolumes and plate counts to the increasing contact time of Photo ClO2 were quite different, with a massive 7 log reduction in viable cells (95% confidence interval [CI]: 6.2, 7.9) but a more moderate 73% reduction in biovolume (95% CI: [60%, 100%]). Results are leveraged to quantitatively assess candidate CSLM experimental designs of thick biofilms. CONCLUSIONS: Photo ClO2 kills biofilm bacteria but only partially removes the biofilm from the surface. To maximize statistical confidence in assessing removal, imaging experiments should use fewer pixels in each z-slice, and more importantly, at least two independent experiments even if there is only a single field of view in each experiment. SIGNIFICANCE AND IMPACT OF STUDY: There is limited penetration depth when collecting 3D confocal images of thick biofilms. Removal can be assessed by optimally fitting Beer's Law to all of the intensities in a 3D image and by accounting for the spatial correlation of the biofilm's surface. For thick biofilms, other image analysis approaches are biased or do not provide error bars. We generate unbiased estimates of removal and assess candidate CSLM experimental designs of thick biofilms with different pixilations, numbers of fields of view and number of experiments using the included design tool.

Application of chlorine dioxide-based hurdle technology to improve microbial food safety-A review.

In recent years, a variety of conventional and novel food sanitation technologies have been developed, among which some may adversely affect the organoleptic properties and the nutrients of foods. The increasing demand for fresh-like foods has promoted efforts for developing innovative technologies. The detrimental effects of some technologies on the sensorial and nutritional values of foods could be overcome by using the hurdle technology that has become a promising approach. The interest in using chlorine dioxide for food sanitation has increased due to its many advantages over chlorine such as its powerful antimicrobial activity and less formation of harmful disinfection by-products. However, using chlorine dioxide to achieve a complete pathogen elimination from foods is still hard. In this context, chlorine dioxide has been combined with other technologies to enhance microbial food safety. This review, therefore, aims to present the application of chlorine dioxide-based hurdle technology through sequential or simultaneous treatments to control foodborne pathogens. The antimicrobial effects of chlorine dioxide combined with thermal and non-thermal physical, chemical, and biological technologies on various foodborne pathogens in a wide range of food commodities are critically reviewed.

Efficient removal of residual lignin from eucalyptus pulp via high-concentration chlorine dioxide treatment and its effect on the properties of residual solids.

In fact, effectively removing lignin from pulp fibers facilitates the conversion and utilization of cellulose. In this study, the residual lignin in eucalyptus pulp was separated using a high concentration of chlorine dioxide. The effects of chlorine dioxide dosage, temperature, and time on lignin removal were investigated. The optimal conditions are chlorine dioxide dosage 5.0%, reaction temperature 40 °C, and reaction time 30 min. The lignin removal yield is 88.21%. The removal yields of cellulose and hemicellulose are 2.28 and 17.00%, respectively. The treated eucalyptus pulp has higher fiber crystallinity and thermal stability. The carbon content on the fiber surface is significantly reduced. The results show that lignin is removed by efficient oxidation, and the degradation of carbohydrates is inhibited using high concentrations of chlorine dioxide at low temperatures and short reaction times. This provides theoretical support for high value conversion of cellulose.

A systematic review on chlorine dioxide as a disinfectant.

The COVID-19 pandemic has tremendously increased the production and sales of disinfectants. This study aimed to systematically review and analyze the efficacy and safety of chlorine dioxide as a disinfectant. The literature relating to the use of chlorine dioxide as a disinfectant was systematically reviewed in January 2021 using databases such as PubMed, Science Direct, and Google Scholar. Inclusion criteria were studies that investigated the use of chlorine dioxide to assess the efficacy, safety, and impact of chlorine dioxide as a disinfectant. Out of the 33 included studies, 14 studies focused on the disinfectant efficacy of chlorine dioxide, 8 studies expounded on the safety and toxicity in humans and animals, and 15 studies discussed the impact, such as water treatment disinfection using chlorine dioxide. Chlorine dioxide is a safe and effective disinfectant, even at concentrations as low as 20 to 30 mg/L. Moreover, the efficacy of chlorine dioxide is mostly independent of pH. Chlorine dioxide can be effectively used to disinfect drinking water without much alteration of palatability and can also be used to destroy pathogenic microbes, including viruses, bacteria, and fungi from vegetables and fruits. Our review confirms that chlorine dioxide is effective against the resistant Mycobacterium, H1N1, and other influenza viruses. Studies generally support the use of chlorine dioxide as a disinfectant. The concentration deemed safe for usage still needs to be determined on a case-by-case basis.

Could polyhexanide and chlorine dioxide be used as an alternative to chlorhexidine? A systematic review

ABSTRACT BACKGROUND: Maintenance of oral microbiota balance is the simplest way to prevent infectious oral diseases, through controlling dental biofilm. Combined use of mouthwash and mechanical removal has been shown to be a very effective way for this. OBJECTIVES: To identify clinical studies comparing the antimicrobial effect and possible adverse effects and/or side effects of chlorhexidine-based mouthwashes with those of mouthwashes containing chlorine dioxide and/or polyhexanide, for controlling oral microbiota. DESIGN AND SETTING: Systematic review designed by the stomatology sector of postgraduation in applied dental sciences of Bauru Dentistry School, University of São Paulo, Brazil. METHODS: A systematic review was conducted using online databases (PubMed, Embase, Web of Science and Science Direct) up to April 8, 2020. The search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: The studies included comprised eight articles published between 2001 and 2017. A total of 295 young adults, adults and elderly people were evaluated (males 44.75% and females 55.25%). Three articles compared polyhexanide with chlorhexidine and five articles compared chlorine dioxide with chlorhexidine. No studies comparing all three mouthwashes were found. The concentrations of the study solutions were quite varied, and all rinses had an antimicrobial effect. In four studies, it was stated that no side effects or adverse effects had been found. Three studies did not address these results and only one study addressed side effects and/or adverse effects. CONCLUSION: Mouthwashes containing chlorine dioxide and polyhexanide are viable alternatives to chlorhexidine, since they reduce oral biofilm and have little or no reported side or adverse effects.

Could polyhexanide and chlorine dioxide be used as an alternative to chlorhexidine? A systematic review.

BACKGROUND: Maintenance of oral microbiota balance is the simplest way to prevent infectious oral diseases, through controlling dental biofilm. Combined use of mouthwash and mechanical removal has been shown to be a very effective way for this. OBJECTIVES: To identify clinical studies comparing the antimicrobial effect and possible adverse effects and/or side effects of chlorhexidine-based mouthwashes with those of mouthwashes containing chlorine dioxide and/or polyhexanide, for controlling oral microbiota. DESIGN AND SETTING: Systematic review designed by the stomatology sector of postgraduation in applied dental sciences of Bauru Dentistry School, University of São Paulo, Brazil. METHODS: A systematic review was conducted using online databases (PubMed, Embase, Web of Science and Science Direct) up to April 8, 2020. The search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: The studies included comprised eight articles published between 2001 and 2017. A total of 295 young adults, adults and elderly people were evaluated (males 44.75% and females 55.25%). Three articles compared polyhexanide with chlorhexidine and five articles compared chlorine dioxide with chlorhexidine. No studies comparing all three mouthwashes were found. The concentrations of the study solutions were quite varied, and all rinses had an antimicrobial effect. In four studies, it was stated that no side effects or adverse effects had been found. Three studies did not address these results and only one study addressed side effects and/or adverse effects. CONCLUSION: Mouthwashes containing chlorine dioxide and polyhexanide are viable alternatives to chlorhexidine, since they reduce oral biofilm and have little or no reported side or adverse effects.

pH-Regulating Nanoplatform for the "Double Channel Chase " of Tumor Cells by the Synergistic Cascade between Chlorine Treatment and Methionine-Depletion Starvation Therapy.

During rapid proliferation and metabolism, tumor cells show a high dependence on methionine. The deficiency of methionine exhibits significant inhibition on tumor growth, which provides a potential therapeutic target in tumor therapy. Herein, ClO2-loaded nanoparticles (fluvastatin sodium&metformin&bupivacaine&ClO2@CaSiO3@MnO2-arginine-glycine-aspatic acid (RGD) (MFBC@CMR) NPs) were prepared for synergistic chlorine treatment and methionine-depletion starvation therapy. After outer layer MnO2 was degraded in the high glutathione (GSH) tumor microenvironment (TME), MFBC@CMR NPs released metformin (Me) to target the mitochondria, thus interfering with the tricarboxylic acid (TCA) cycle and promoting the production of lactate. In addition, released fluvastatin sodium (Flu) by the NPs acted on monocarboxylic acid transporter 4 (MCT4) in the cell membrane to inhibit lactate leakage and induce a decrease of intracellular pH, further prompting the NPs to release chlorine dioxide (ClO2), which then oxidized methionine, inhibited tumor growth, and produced large numbers of Cl- in the cytoplasm. Cl- could enter mitochondria through the voltage-dependent anion channel (VDAC) channel, which was opened by bupivacaine (Bup). The disruption of Cl- homeostasis promotes mitochondrial damage and membrane potential decline, leading to the release of cytochrome C (Cyt-C) and apoptosis inducing factor (AIF) and further inducing cell apoptosis. To sum up, the pH-regulating and ClO2-loaded MFBC@CMR nanoplatform can achieve cascade chlorine treatment and methionine-depletion starvation therapy toward tumor cells, which is of great significance for improving the clinical tumor treatment effect.