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The Safety of Low Concentration Hypochlorous Acid as an Oral Gargle Solution and Its Anti-Microbial Effects
Abstract
The authors aimed to evaluate the safety of low concentration hypochlorous acid as an oral gargle solution. To do this, we carried out in vitro and in vivo experiments and evaluated its efficacy by compared with normal saline and chlorhexidine gargle using throat culture before and after gargling.
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Cystic fibrosis is a debilitating lung disease due to mutations in the cystic fibrosis transmembrane conductance regulator protein (CFTR) and is associated with chronic infections resulting in elevated myeloperoxidase activity and generation of hypochlorous acid (HOCl). CFTR mutations lead to decreased levels of glutathione (GSH) and thiocyanate (SCN) in the epithelial lining fluid (ELF). Hypertonic saline is used to improve lung function however the mechanism is uncertain.
In the present study, the effect of GSH and SCN on HOCl-mediated cell injury and their changes in the ELF after hypertonic saline nebulization in wild type (WT) and CFTR KO mice was examined. CFTR sufficient and deficient lung cells were assessed for GSH, SCN and corresponding sensitivity towards HOCl-mediated injury, in vitro.
CFTR (-) cells had lower extracellular levels of both GSH and SCN and were more sensitive to HOCl-mediated injury. In vivo, hypertonic saline increased ELF GSH in the WT and to a lesser extent in the CFTR KO mice but only SCN in the WT ELF. Finally, potential protective effects of GSH and SCN at concentrations found in the ELF against HOCl toxicity were examined in vitro.
While the concentrations of GSH and SCN associated with the WT ELF protect against HOCl toxicity, those found in the CFTR KO mice were less sufficient to inhibit cell injury. These data suggests that CFTR has important roles in exporting GSH and SCN which are protective against oxidants and that hypertonic saline treatment may have beneficial effects by increasing their levels in the lung.
Oxidative degradation of biological substrates by hypochlorous acid has been examined under reaction conditions similar to those found in active phagosomes. Iron sulfur proteins are bleached extremely rapidly, followed in decreasing order by beta-carotene, nucleotides, porphyrins, and heme proteins. Enzymes containing essential cysteine molecules are inactivated with an effectiveness that roughly parallels the nucleophilic reactivities of their sulfhydryl groups. Other compounds, including glucosamines, quinones, riboflavin, and, except for N-chlorination, phospholipids, are unreactive. Rapid irreversible oxidation of cytochromes, adenine nucleotides, and carotene pigments occurs when bacterial cells are exposed to exogenous hypochlorous acid; with Escherichia coli, titrimetric oxidation of cytochrome was found to coincide with loss of aerobic respiration. The occurrence of these cellular reactions implicates hypochlorous acid as a primary microbicide in myeloperoxidase-containing leukocytes; the reactivity patterns observed are consistent with the view that bactericidal action results primarily from loss of energy-linked respiration due to destruction of cellular electron transport chains and the adenine nucleotide pool.
Pharyngodynia, or sore throat, is one of the symptoms most frequently reported by patients to primary care physicians.
The purpose of this study was to compare the efficacy and tolerability of mouthwash formulations of ketoprofen lysine salt (KLS), an anti-inflammatory agent, and benzydamine hydrochloride (BH), a local anesthetic, in patients with acute inflammation of the pharyngeal cavity.
In this randomized, multicenter, parallel-group, single-blind study, patients (who were blinded) were assigned to receive undiluted BH 15 mL (22.5 mg) or KLS 10 mL (160 mg) diluted in 100 mL of water. Both agents were gargled twice daily until pain remission or up to 7 days. A physical examination of the oropharyngeal cavity was performed, and severity of edema and hyperemia was assessed after 3 days of treatment and, if symptoms had not resolved, after pain remission.
Of the 241 patients (120 KLS, 121 BH), 239 were included in the safety analysis and 232 were in the intent-to-treat population. The differences between groups in the duration of analgesic effect after the first dose of drug and the time course of pain were found to be statistically significant (P = 0.006 and P = 0.017, respectively), favoring KLS. Adverse drug-related effects reported included numbness of the tissues in the oral cavity, sensation of tingling in the tissues in the oral cavity, dry mouth, thirst, and nausea. A significantly greater proportion of BH-treated patients reported adverse events (P = 0.001 for all adverse events and drug-related adverse events).
KLS mouthwash exerts a significantly longer first-application analgesic action with significantly greater local tolerability than BH in patients with pharyngeal pain of inflammatory and/or infectious origin.
BACKGROUND: Low concentrations of hypochlorous acid (HOCl) have been shown to exhibit both antibacterial and anti-influenza virus activity, but HOClstill has not been used to kill human rhinovirus (HRV). To model the antiviral effect of nasal irrigation with low-level HOCl in patients with the common cold, we tested the effects of a low concentration of HOCl on HRV infection of primary human nasal epithelial cells (HNEC).METHODS: Cells were infected with HRV for 24 hours and treated with HOCl three times, for 5 minutes each time, at 12 hour intervals. The effects of HOCl on rhinovirus-induced secretion of IL-6 and IL-8 were assessed by ELISA and HRV replication was determined by viral titration.RESULTS: HOCl treatment significantly inhibited HRV-induced secretion of IL-6 and IL-8 and significantly reduced viral titer. The effects of HOCl peakedat 1 minute after HOCl generation and decreased thereafter.CONCLUSION: These in vitro findings indicate that nasal irrigation with low-level HOCl solution may improve clinical symptoms in patients with thecommon cold.
To evaluate the impact of oral health on the evolution of nosocomial infections and to document the effects of oral antiseptic decontamination on oral health and on the rate of nosocomial infections in patients in a surgical intensive-care unit (ICU).
A prospective, randomized, double-blind, placebo-controlled clinical trial.
Surgical ICU in University Hospital Dubrava.
The study included 60 nonedentulous patients consecutively admitted to the surgical ICU and requiring a minimum stay of three days.
After randomization, the treatment group underwent antiseptic decontamination of dental plaque and the oral mucosa with chlorhexidine gel. The control group was treated with placebo gel. Dental status was assessed using a caries-absent-occluded (CAO) score, and the amount of plaque was assessed using a semi-quantitative score. Samples of dental plaque, oral mucosa and nasal and tracheal aspirates were collected for bacterial culture, and nosocomial infections were assessed.
The plaque score significantly increased in the control group and decreased in the treated patients. Patients who developed a nosocomial infection had higher plaque scores on admission and during their ICU stay. The control group showed increased colonization by aerobic pathogens throughout their ICU stay and developed nosocomial infections (26.7%) significantly more often than the treated patients (6.7%); the control group also stayed longer in the ICU (5.1 +/- 1.6 vs. 6.8 +/- 3.5 days, P = 0.019). Furthermore, a trend in reduction of mortality was noted in the treated group (3.3% vs. 10%).
Among surgical ICU patients, poor oral health had a significant positive correlation with bacterial colonization and the evolution of nosocomial infections. Oral decontamination with chlorhexidine significantly decreased oropharyngeal colonization, the incidence of nosocomial infections, length of ICU stay, and mortality in these patients.
Saline irrigation would be more effective for chronic sinusitis patients if it had bactericidal effects. Low concentrations of hypochlorous acid may be used as a nasal irrigation solution. First, we developed a 0.85% NaCl solution by adding NaCl to tap water (pH 7.0 and 8.4) and measuring the concentration of free chlorine and hypochlorous acid after giving the solution a short electrical impulse of 20 seconds. Then we investigated whether the derived hypochlorous acid had a toxic effect on human primary nasal epithelial cells, if and what effect it had on the expression of mucin genes, and, finally, if it had bactericidal, fungicidal, or virucidal effects.
In vitro biochemical experiment.
We treated human primary nasal epithelial cells with 3.5 ppm of hypochlorous acid and then examined the cells for cytotoxicity. We also investigated the bactericidal, fungicidal, and virucidal effects by challenging the cells with the following microorganisms Aspergillus fumigatus, Haemophilus influenzae, Klebsiella pneumoniae, Rhizopus oryzae, Candida albicans, Methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes. To study the virucidal effects of HOCl, we used the human influenza A virus to challenge the cells.
: In the cytotoxicity assay and in the morphological examination, the cells did not show anytoxicity at 30 minute or 2 hours after treatment with HOCl. More than 99% of bactericidal or fungicidal activity was noted for all species, except for Candida albicans, in tap water at either pH 7.0 or 8.4. In addition, a 3.2-log10 reduction was achieved in cells challenged with the human influenza A virus.
A low concentration HOCl solution can be used as an effective nasal irrigation solution.
The effect of duration of orally administered penicillin V potassium on the bacteriologic and clinical cure of group A streptococcal pharyngitis was evaluated. One hundred ninety-one middle-class patients received either seven days (96 patients) or ten days (95 patients) of therapy. Compliance with taking penicillin was assessed by multiple methods, including penicillinuria. Throat cultures were obtained during therapy and three times in the three weeks after therapy. M-precipitin and T-agglutinin typing were done on paired isolates of group A streptococci from patients who had recurrences. Patients treated for seven days had a significantly greater failure rate (30/96 [31%]) compared with patients receiving ten days of penicillin (17/95 [18%]). Compliance rates were high; 66% to 81% of patients showed penicillinuria throughout the study period. Treatment failure was not a function of poor compliance in either treatment group. The data support the current recommendation for ten full days of penicillin therapy and suggest that persistence of streptococci in the throat after adequate therapy may be common.
1. Some biochemical and pathophysiological aspects of hypochlorous acid (as major oxidant species produced by activated white blood cells) are discussed. 2. Moreover, we have discussed the problem of the pharmacological scavenging of hypochlorous acid, focusing attention on the biochemical tests able to study therapeutically relevant scavenging properties of various drugs against hypochlorous acid itself.
Oral care is of great importance in the prevention of chemotherapy-induced oropharyngeal mucositis. Although considerable attention has been given in improving oral care practices, patients' acceptance and tolerance of oral rinses is a continuing problem in oral care. A randomized crossover design was used to determine the relative acceptability and tolerability of chlorhexidine and benzydamine oral rinse agents in children receiving chemotherapy. At the end of the study, each subject was asked to compare these two agents in relation to stinging and taste, as well as his/her perception in reducing mucositis. Thirty-four children aged 6-17 years completed two courses of chemotherapy during which they alternately practiced oral care using chlorhexidine then benzydamine or benzydamine then chlorhexidine. All of the children tolerated the agents well and continued with rinsing throughout the study. Only a few children had to resort to diluting the agents with normal saline or water. Fifty-nine percent of children reported that the stinging associated with benzydamine was more accepted than chlorhexidine. The taste of both these agents was accepted by 50% of children. Approximately 60% of children reported that chlorhexidine was more helpful than benzydamine in reducing mucositis. About 47% and 50% of them preferred chlorhexidine and benzydamine in their subsequent chemotherapy, respectively. In conclusion, chlorhexidine and benzydamine are acceptable and well-tolerated by children over the age 6 years old.