Molecular docking study of frequently used food additives for selected targets depending on the chromosomal abnormalities they cause.

Food additives (FAs) (flavor enhancers, sweeteners, etc.) protect foods during storage and transportation, making them attractive to consumers. Today, while the desire to access natural foods is increasing, the chemicals added to foods have started to be questioned. In this respect, genotoxicity tests have gained importance. Studies show that some food additives may have genotoxic risks. Previous studies carried out in our laboratory also revealed genotoxic effects of Monopotassium glutamate (MPG), Monosodium glutamate (MSG), Magnesium diglutamate (MDG) as flavor enhancers; Potassium benzoate (PB), Potassium sorbate (PS), Sodium benzoate (SB), Sodium sorbate (SS) as preservatives; Acesulfame potassium (ACE-K), Xylitol (XYL) as sweeteners. In this study, we determined the interactions of these food additives with ATM and p53 proteins, which are activated in the cell due to genotoxic effects, and with DNA by employing the molecular docking method for the first time. Among the food additives, SB (-4.307) for ATM, XYL (-4.629) for p53, and XYL (-4.927) for DNA showed the highest affinity. Therefore, flexible docking (IFD) scores were determined for SB, XYL, and MDG from flavor enhancers. The potential binding modes of the food additives to target molecules' possible inhibition mechanisms were determined by molecular docking. Thus, new information was obtained to show how these additives cause chromosomal abnormalities.

Biomatrix of health risk assessment of benzene-exposed workers at Thai gasoline stations.

OBJECTIVE: This study assessed the health risk of benzene exposure among Thai gasoline station workers through biomarker detection and experience of adverse symptoms. METHODS: Trans, trans-muconic acid (tt-MA) metabolites of benzene were analyzed from spot urine sampled among gasoline station workers after shift work using HPLC-UV. Air benzene monitoring was done with an active sampler connected to a charcoal sorbent tube, and analyzed by GC-FID. The health risk was calculated by using the biomatrix of the likelihood of benzene exposure and the severity of adverse symptoms. RESULTS: The tt-MA concentration, among 235 workers, ranged from less than 10-2159 µg/g Cr, which corresponded to the air benzene concentration range of <0.1 to 65.8 ppb. In total, 32.3% of workers had a higher than acceptable risk level and there was a significant association between gasoline station work zones and the likelihood of benzene exposure as well as the health risk of workers. The health risk levels estimated from the biomarker monitoring were consistent with the risk matrix of air benzene monitoring. CONCLUSION: This tt-MA biomarker monitoring and biomatrix of health risk assessment is suggested as useful for health surveillance of gasoline station workers exposed to benzene.

Antimicrobial activity of organic acids against Campylobacter spp. and development of combinations-A synergistic effect?

Contaminated poultry meat is considered to be the main source of human infection with Campylobacter spp., a pathogen that asymptomatically colonizes broiler chickens during fattening and contaminates carcasses during slaughter. To prevent or reduce the colonization of broiler flocks with Campylobacter spp., applying different organic acids, especially in combinations, via feed or drinking water seems to be a promising approach. However, only very few combinations of organic acids have been tested for their antibacterial efficacy against Campylobacter spp. Therefore, the in vitro susceptibility of 30 Campylobacter spp. isolates (20 C. jejuni and ten C. coli) to ten organic acids and ten combinations was determined. The testing of minimum inhibitory concentration (MIC) values was performed at pH 6.0 and 7.3 by using the broth microdilution method and included the following organic acids: Caprylic acid, sorbic acid, caproic acid, benzoic acid, ascorbic acid, propionic acid, acetic acid, formic acid, fumaric acid and tartaric acid and combinations thereof. The lowest MIC values were seen for caprylic acid (MIC range at pH 7.3: 0.5-2 mmol/L) and sorbic acid (MIC range at pH 7.3: 1-4 mmol/L). One to two dilution steps lower MIC values were determined at the lower pH value of 6.0. Furthermore, ten combinations consisting of three to five organic acids were developed. In addition to the tested antibacterial activity, other criteria were included such as approval as feed additives, reported synergistic effects and chemical properties. For nine of ten combinations, the MIC90 values of the organic acids decreased 1.25- to 241.5-fold compared to the MIC90 values for the individual substances. Furthermore, nine of ten combinations exhibited synergistic activities against two or more of the tested C. jejuni and C. coli isolates. A combination of caprylic acid, sorbic acid and caproic acid exhibited synergistic activities against the largest number of Campylobacter spp. isolates (six C. jejuni and four C. coli) with fractional inhibitory concentration (FIC) indices (∑FIC) ranging from 0.33 to 1.42. This study shows in vitro synergistic activities of different organic acids in combinations against the major Campylobacter species and could therefore be a promising basis for reducing Campylobacter spp. in vivo.

Comparative biocompatibility and antimicrobial studies of sorbic acid derivates.

Nowadays, the sorbates are the third largest group of antimicrobial preservatives in food and pharmaceutical industries, following the parabens and benzoates whose safety is questioned by recent publications. A disadvantage of sorbates is their pH dependence, as their antimicrobial effect is greatly reduced in alkaline environment. The main, widely used sorbate derivatives are sorbic acid and potassium sorbate, no sorbic acid esters are involved in current industrial application. We aimed to test whether the esters of sorbic acid are capable to extend the antimicrobial spectrum of the original molecule while maintaining its advantageous biocompatibility profile. A comparative biocompatibility study of different derivatives (sorbic acid, potassium sorbate, isopropyl sorbate and ethyl sorbate) was carried out. In vitro cell viability assays of MTT (2-(4,5-dimethyl-2-thiazolyl)-3,5-diphenyl-2H-tetrazolium bromide), Neutral Red (3-amino-7-dimethylamino-2-methylphenazine hydrochloride) and flow cytometry with propidium iodide and annexin were performed on Caco-2 cells. In case of in vivo toxicity study, G. mellonella larvae were injected with different concentrations of the test compounds. Time-kill tests were executed on reference strains of C. albicans, E. coli, and S. aureus. According to the MTT-assay, the IC50 values were the following: ethyl sorbate, sorbic acid <0.045% w/w, isopropyl sorbate 0.32% w/w, potassium sorbate >0.75% w/w, while Neutral Red values were >0.75% w/w for the esters and potassium sorbate and 0.66% w/w for sorbic acid. Flow cytometry results indicated the higher cell damage in case of isopropyl sorbate. However, the cytotoxic results of isopropyl sorbate, in vivo toxicity study on G. mellonella larvae did not show significant mortality. It was found, that the antimicrobial properties of isopropyl sorbate were outstanding compared to sorbic acid and potassium sorbate. These results indicate, that the use of sorbate esters can be advantageous, hence, further toxicity studies are needed to prove their safety.

Potassium sorbate suppresses intestinal microbial activity and triggers immune regulation in zebrafish (Danio rerio).

Potassium sorbate (PS) is a class of bacteriostatic antiseptic agent widely used in the food industry; the effects of its intake on host health are currently unclear. In the present study, zebrafish (Danio rerio) were exposed to 0.1 g L-1 and 1 g L-1 aqueous solutions of PS for 2 weeks to investigate the impact of PS on the microecological balance of the intestinal microbiota and immune system. PS exposure triggered immune regulation of zebrafish, significantly reducing the content of diverse biomarkers in the gut, including Immunoglobulin G (IgG), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). Based on high-throughput sequencing data, it was observed that PS exposure resulted in some destabilization of the microbiome composition of the zebrafish, which mainly manifested as a reduction in the abundance of specific genera and the relative levels of transcription and carbohydrate metabolism related to microbial reproductive ability and activity. These changes were consistent with the activity index of microbiota (AIM), a novel measure that we constructed. Collectively, these results illustrate that PS can affect the immune system of zebrafish by changing the composition and function of the gut microbiota, and inhibiting the metabolism of the intestinal microbiota. Our study offers a new understanding of the toxicity of PS.

Molecular and technical aspects on the interaction of serum albumin with multifunctional food preservatives.

Synthetic food preservatives like sodium acetate (SA), sodium benzoate (SB), potassium sorbate (PS) and Butyl paraben (BP) have been widely used in food and pharmacy industries. One of the toxicological aspects of food additives is evaluation of their interaction with serum proteins such as albumin. These additives interaction with human serum albumin (HSA) can exert considerable effect on the absorption, distribution, metabolism and toxicity of chemical compounds. It should be noticed that the aforementioned food preservatives intake increase mainly in the presence of glucose may lead to complex formation of SA, SB, PS and BP with HSA and accelerate the development of variety disease such as cancer, diabetes, multiple sclerosis, brain damage, nausea and cardiac disease. Therefore, to understand the mechanisms of aforementioned food additives interaction and conformational changes of proteins, we aim to review various studies that investigated albumin interaction with these additives using several procedures.

Assessment of sodium benzoate and potassium sorbate preservatives in some products in Kashan, Iran with estimation of human health risk.

The purpose was to assess of sodium benzoate (SB) and potassium sorbate (PS) preservatives in 103 samples of cake, toast bread, tomato paste, mayonnaise sauce, carbonated soft drink and Olovieh salad in Kashan, by spectrophotometry and high performance liquid chromatography (HPLC) methods. The chronic daily intake (CDI), target hazard quotient (THQ) and hazard index (HI) of SB and PS for Iranian population were calculated. The results showed that SB and PS were not detected in the tomato paste samples. SB and PS concentrations for all samples were less than regulatory limits except for PS in one cake sample (3.57%). CDI and THQ of PS for mayonnaise sauce, Olovieh salad and cake products, except toast bread, were less than the acceptable daily intakes (ADIs) and one, respectively. While HI value of PS for the selected products was more than one, indicating that the non-carcinogenic risk represent a threat to consumers. THQ and HI values of SB for mayonnaise sauce and carbonated soft drink products were more than one through consumption of these products, indicating considerable non-carcinogenic risk. Therefore, the results highlighted the importance of a more attentive monitoring of these preservatives by the public and food health authorities in Iran.

Safety assessment of sodium acetate, sodium diacetate and potassium sorbate food additives.

Cytotoxicity and genotoxicity of sodium acetate (SA), sodium diacetate (SDA), and potassium sorbate (PS) was tested on Human Umbilical Vein Endothelial Cells (HUVEC). Cytotoxicity was investigated by MTT assay and flow cytometry analysis, while genotoxicity was evaluated using DNA fragmentation and DAPI staining assays. The growth of treated HUVECs with various concentrations of SA, SDA and PS decreased in a dose-and time-dependent manner. The IC50 of 487.71, 485.82 and 659.96 µM after 24 h and IC50 of 232.05, 190.19 and 123.95 µM after 48 h of treatment were attained for SA, SDA and PS, respectively. Flow cytometry analysis showed that early and late apoptosis percentage in treated cells was not considerable. Also neither considerable DNA fragmentation nor DNA smear was observed using DAPI staining and DNA ladder assays. Overall, it can be concluded that the aforementioned food additives can be used as safe additives at low concentration in food industry.

Comparative toxic effects of butylparaben sodium, sodium diacetate and potassium sorbate to Dunaliella tertiolecta and HL7702 cells.

Butylparaben sodium (BP), sodium diacetate (SDA) and potassium sorbate (PS) are safe and internationally recognized preservatives. The aim of this study is to further evaluate their toxicities using microalgae cells, and a comparison is made with their mammalian cell cytotoxicities. Unicellular Dunaliella tertiolecta, was employed to test the possible toxicities of BP, SDA and PS. The results show that the three preservatives have a negative effect on D. tertiolecta, as manifested by a strong decrease in chlorophyll and carotenoid content, viable algal cells, and superoxide dismutase (SOD) and catalase (CAT) activities. SDA and PS had small effects on the normal hepatocytes HL7702, but similar to that for MCF-10A cells, BP is toxic. The effective concentration (EC50) value for HL7702 is 215.97 mg L-1. It is concluded that BP, SDA and PS have low toxicities to D. tertiolecta under slightly alkaline conditions, while under acidic conditions, SDA has moderate toxicity and PS has high toxicity. The sensitivity of algal cells is higher than that of HL7702 cells under slightly alkaline conditions, and is even more sensitive under acidic conditions. D. tertiolecta can be used as a pre-screen for toxicity testing.

Benzene exposure is associated with cardiovascular disease risk.

Benzene is a ubiquitous, volatile pollutant present at high concentrations in toxins (e.g. tobacco smoke) known to increase cardiovascular disease (CVD) risk. Despite its prevalence, the cardiovascular effects of benzene have rarely been studied. Hence, we examined whether exposure to benzene is associated with increased CVD risk. The effects of benzene exposure in mice were assessed by direct inhalation, while the effects of benzene exposure in humans was assessed in 210 individuals with mild to high CVD risk by measuring urinary levels of the benzene metabolite trans,trans-muconic acid (t,t-MA). Generalized linear models were used to assess the association between benzene exposure and CVD risk. Mice inhaling volatile benzene had significantly reduced levels of circulating angiogenic cells (Flk-1+/Sca-1+) as well as an increased levels of plasma low-density lipoprotein (LDL) compared with control mice breathing filtered air. In the human cohort, urinary levels of t,t-MA were inversely associated several populations of circulating angiogenic cells (CD31+/34+/45+, CD31+/34+/45+/AC133-, CD34+/45+/AC133+). Although t,t-MA was not associated with plasma markers of inflammation or thrombosis, t,t-MA levels were higher in smokers and in individuals with dyslipidemia. In smokers, t,t-MA levels were positively associated with urinary metabolites of nicotine (cotinine) and acrolein (3-hydroxymercapturic acid). Levels of t,t-MA were also associated with CVD risk as assessed using the Framingham Risk Score and this association was independent of smoking. Thus, benzene exposure is associated with increased CVD risk and deficits in circulating angiogenic cells in both smokers and non-smokers.

MiR-34a, a promising novel biomarker for benzene toxicity, is involved in cell apoptosis triggered by 1,4-benzoquinone through targeting Bcl-2.

Exposure to benzene is inevitable, and concerns regarding the adverse health effects of benzene have been raised. Most investigators found that benzene exposure induced hematotoxicity. In this regard, Our study aimed to explore a novel potential biomarker of adverse health effects following benzene exposure and the toxic mechanisms of benzene metabolites in vitro. This study consisted of 314 benzene-exposed workers and 288 control workers, an air benzene concentration of who were 2.64 ± 1.60 mg/m3 and 0.05 ± 0.01 mg/m3, respectively. In this population-based study, miR-34a expression was elevated in benzene-exposed workers. The correlation of miR-34a with the airborne benzene concentration, S-phenylmercapturic acid (S-PMA) and trans, trans-muconic acid (t, t-MA), all of which reflect benzene exposure, was found. Correlation analysis indicated that miR-34a was associated with peripheral blood count, alanine transaminase (ALT) and oxidative stress. Furthermore, multivariate analysis demonstrated that miR-34a expression was strongly associated with white blood cell count (structure loadings = 0.952). In population-based study, miR-34a had the largest contribution to altered peripheral blood counts, which reflect benzene-induced hematotoxicity. The role of miR-34a in benzene toxicity was assessed using lentiviral vector transfection. Results revealed that 1,4-benzoquinone induced abnormal cell apoptosis and simultaneously upregulated miR-34a accompanied with decreased Bcl-2. Finally, inhibition of miR-34a elevated Bcl-2 and decreased 1,4-benzoquinone-induced apoptosis. In conclusion, miR-34a was observed to be involved in benzene-induced hematotoxicity by targeting Bcl-2 and could be regarded as a potential novel biomarker for benzene toxicity.

Investigation of local anesthetic and antimycobacterial activity of Ottonia martiana Miq. (Piperaceae).

Ottonia martiana is a plant popularly known in Brazil by the use for toothache. Ethanolic extract (EE), hexane fraction (HF), dichloromethane fraction (DF) and piperovatine obtained from O. martiana were assayed in vitro and in vivo. The acute toxicity of EE was determined, and LD50 values of 164.5 and 65.0 mg/kg by the oral and intraperitoneal routes, respectively, indicated a high toxicity for EE in vivo, explaining its popular use by topical administration only. A local anesthetic-like effect of EE and its fractions was observed in experimental models using pain induction, and such effect involved an analgesic action. The antimycobacterial activity of EE, HF, DF and piperovatine was evaluated against Mycobacterium tuberculosis H37Rv ATCC 27924. EE, HF, DF, and piperovatine showed a potential antimycobacterial effect with MICs of 16.0, 62.0, 62.0 and 8.0 µg/mL, respectively. Piperovatine was more effective than the EE or the other fractions. The selectivity index (SI=IC50/MIC) values calculated for EE, HF, DF and piperovatine based on the MICs and the cytotoxicity against J774 macrophages (IC50 by MTT assay) revealed values of 6.43, 2.34, 1.5 and 9.66, respectively.

Comparative toxicity of physiological and biochemical parameters in Euglena gracilis to short-term exposure to potassium sorbate.

Potassium sorbate is the potassium salt of sorbic acid, is a widespread and efficient antioxidant that has multiple functions in plants, traditionally associated with the reactions of photosynthesis; however, it has moderate toxicity to various species including rat, fish, bacteria and human health. The effects of potassium sorbate on the movement and photosynthetic parameters of Euglena gracilis were studied during short-term exposure. Potassium sorbate showed acute toxicity to the green flagellate E. gracilis affecting different physiological parameters used as endpoints in an automatic bioassay such as motility, precision of gravitational orientation (r-value), upward movement and alignment, with mean EC50 values of 2867.2 mg L(-1). The concentrations above 625 mg L(-1) of potassium sorbate induce an inhibition of the photosynthetic efficiency and electron transport rate and, in concentrations more than 2500.0 mg L(-1), the Euglena cells undergo a complete inhibition of photosynthesis even at low light irradiation.

The natural compounds piperovatine and piperlonguminine induce autophagic cell death on Trypanosoma cruzi.

The currently available treatments for Chagas disease show limited therapeutic potential and are associated with serious side effects. Our group has been attempting to find alternative drugs isolated from natural products as a potential source of pharmacological agents against Trypanosoma cruzi. Here, we demonstrate the antitrypanosomal activity of the amides piperovatine and piperlonguminine isolated from Piper ovatum against epimastigotes and intracellular amastigotes. We also investigated the mechanisms of action of these compounds on extracellular amastigote and epimastigote forms of T. cruzi. These amides showed low toxicity to LLCMK(2) mammalian cells. By using transmission and scanning electron microscopy, we observed that the compounds caused severe alterations in T. cruzi. These alterations were mainly located in plasma membrane and mitochondria. Furthermore, the study of treated parasites labeled with Rh123, PI and MDC corroborate with our TEM data. These mitochondrial dysfunctions induced by the amides might trigger biochemical alterations that lead to cell death. Altogether, our data evidence a possible autophagic process.

Transcriptomic and phenotypic responses of Listeria monocytogenes strains possessing different growth efficiencies under acidic conditions.

In an experiment delineating aciduric strains, food and clinical Listeria monocytogenes isolates tended to produce the most biomass whereas ovine and avian strains produced comparatively less biomass when exposed to high levels of sodium diacetate (SD) and potassium sorbate. Compared to reference strains that exhibited greater acid sensitivity, representative food isolates with comparatively good growth capacities in the presence of 21 mM SD at pH 5.0 accumulated reduced levels of acetate anion and K(+) ion. The aciduric nature of SD-resistant strains was also reflected by comparatively high tolerance to pH 2.4 (HCl) acid challenges, a property boosted by the presence of SD. Exposure to elevated levels of SD (21 mM SD at pH 5.0) was found to have broad effects on gene expression, as differentiated from effects caused by mildly acidic conditions (pH 5.0). SD-resistant strain FW04/0025 was more responsive to elevated SD, increasing the expression of 222 genes (>2-fold change [P < 0.05]), compared to the more sensitive EGD reference strain, which exhibited increases in expression of 112 genes. Key differences between the strains in relation to SD-enhanced transcripts were notably associated with the cell envelope, oxidative stress management, and intermediary metabolism. SD thus appears to differentially influence growth efficiency and survival of strains, under conditions relevant to acidic foods, that could be due to altered cell wall and metabolic phenotypes.

Comparison of preservative-induced toxicity on monolayer and stratified Chang conjunctival cells.

Preservatives are used in ocular medications to prevent microbial contamination. The use of benzalkonium chloride (BAC), the most widely used preservative in ocular medications, has been scrutinized with a number of studies indicating its toxicity to monolayer cultures of corneal and conjunctival epithelial cells. The purpose of this study was to evaluate and compare the toxicity of BAC and other preservatives and common components of ocular formulations on monolayer and stratified air-lifted cultures of Chang conjunctival cells. Air-lifting Chang cells grown on transwell filters increased stratification as assessed by transepithelial electrical resistance and histology. Unlike monolayer cultures in which ocular medications containing BAC caused near complete loss of cell viability, stratified, air-lifted cultures were not affected by the presence of BAC in ocular medications with up to 30-min exposures. Stratification shifted the dose-response curve to the right for benzalkonium chloride, thimerosal, chlorhexidine digluconate, potassium sorbate and EDTA. These results demonstrate that stratification significantly affects cell viability of Chang conjunctival cells in response to preservatives and additives of ophthalmic preparations.

Does potassium sorbate induce genotoxic or mutagenic effects in lymphocytes?

The present study evaluates the genotoxic potential of potassium sorbate (PS) in cultured and isolated human lymphocytes. To assess the damage caused by PS in humans, we designed in vitro experiments by measuring chromosomal aberrations (CAs), sister-chromatid exchanges (SCEs), micronucleus (MN) and comet assays. Lymphocytes were treated with negative control (sterile distilled water), positive control (MMC for cultured lymphocytes, and H(2)O(2) for isolated lymphocytes) and four concentrations (125, 250, 500, and 1000 microg/ml) of PS. According to the results, PS treatment significantly increases the CAs (with or without gaps at 500 and 1000 microg/ml concentrations) and SCEs (at 250, 500, 1000 microg/ml for 24h and 125, 250, 500, 1000 microg/ml for 48h) compared with vehicle control. Following treatment of the isolated lymphocytes for 1h, significant PS-induced DNA strand breaks were observed, at all concentrations. However, PS failed to significantly affect the MN assay. On the contrary, PS does not cause cell cycle delay as noted by the non-significant decrease in the cytokinesis-block proliferation index (CBPI) and replicative index (RI). Only a slight decrease was observed in the mitotic index (MI) at the highest concentration for both treatment times. From the results, PS is clearly seen to be genotoxic to the human peripheral blood lymphocytes in vitro.

Cytogenetic study in cultured human lymphocytes treated with three commonly used preservatives.

Potassium sorbate, sodium benzoate and potassium nitrate have been tested for their genotoxic, cytostatic and cytotoxic potential in human peripheral blood cells in vitro. Potassium nitrate has shown no activity in the test system. When potassium sorbate and sodium benzoate were used at concentrations of 2.0, 0.2 and 0.02 mM no cytostatic activity was detected. However, concentrations of 4 and 8 mM have shown a weak cytostaticity. Additionally, a genotoxic activity using the SCE methodology has been observed at 8 mM of sodium benzoate and at 4 and 8 mM of potassium sorbate. No cytotoxic activity has been induced by the three preservatives. Data demonstrate that the preservatives at low concentrations can be considered as non genotoxic under conditions tested.

Green tea attenuates benzene-induced oxidative stress in pump workers.

Workers exposed to benzene frequently suffer from toxicities of the bone marrow as well as the central nervous, immune, and reproductive systems. This toxicity most likely is a result of the oxidative metabolism of benzene to reactive products. As green tea possesses antioxidant effects, the objective of this study was to examine any amelioration of benzene-induced oxidative stress in pump workers drinking 6 cups (150 ml/cup) of freshly prepared tea daily. Sixty male non-smoking subjects, divided into four groups: no benzene exposure/no green tea; no exposure/tea; exposure/no tea; and, exposure/tea, were monitored after a 6 mo period. On the final day of the study, urine samples were collected for analyses of benzene, trans-trans muconic acid, and phenol. Blood was also collected at this time; plasma was assayed for total antioxidant activity, malondialdehyde (MDA), and glutathione (GSH) while erythrocytes were analyzed for activity of antioxidant enzymes glutathione peroxidase (GSHPX), superoxide dismutase (SOD), and catalase. The results demonstrated that urinary levels of benzene, trans-trans muconic acid, and phenol were elevated in all pump workers, and that this elevation was mitigated by consumption of green tea. The benzene exposures also led to significant reductions in plasma GSH levels and erythrocyte antioxidant enzyme activities; these effects were abrogated (to near-control levels) by the tea. Interestingly, among control subjects, tea ingestion itself caused significant increases in both GSHPX and catalase activities. Unlike with the other plasma parameters, while the benzene exposures also significantly increased plasma MDA levels and decreased total antioxidant activity, tea ingestion did not cause a near-total reversion to control values; the effects on these two endpoints were more like those noted with the urine parameters (mitigation, not abrogation). These studies demonstrate that drinking green tea during benzene exposure can reduce several parameters indicative of oxidative stress. As such, as a dietary supplement, green tea could represent a potential therapeutic agent in reducing certain aspects of benzene-induced toxicity.

In vitro effects of preservatives in nasal sprays on human nasal epithelial cells.

BACKGROUND: The preservatives benzalkonium chloride and potassium sorbate are widely used in nasal drops and sprays. Recently, side effects resulting from mucosal damage caused by benzalkonium chloride and potassium sorbate were reported. METHODS: We investigated the toxicity of benzalkonium chloride and potassium sorbate on human nasal epithelial cells in vitro. Using primary human nasal epithelial cells, different concentrations of benzalkonium chloride, potassium sorbate, or phosphate-buffered saline (PBS; control group) solutions were cocultured with nasal epithelial cells for 15 minutes. Then, the viability of the cells and the cell morphology were assessed. RESULTS: Nasal epithelial cells were more severely damaged with use of clinical preparations or higher concentrations of benzalkonium chloride than in the control group. In addition, nasal epithelial cell membrane lysis was seen on electronic microscopy in the benzalkonium chloride groups. In contrast, there was no significant cell damage seen in the potassium sorbate groups compared with the control group, even with higher concentrations than clinically used. CONCLUSION: Potassium sorbate appears to be a relatively safer preservative than benzalkonium chloride for use in nasal sprays and drops in vitro study.