RESUMEN
Sodium benzoate (SB), the sodium salt of benzoic acid, is a food preservative with wide applications in the food, cosmetic and pharmaceutical industries due to its ability to kill many microorganisms effectively. Experimental evidence however suggests that excessive intake of SB poses detrimental health risks among consumers in the population. The present study investigated the toxic effects of various concentrations of SB using Drosophila melanogaster as a model. Adult wild-type flies of Canton S strain (1- to 3-days old) was orally exposed to SB (0, 0.5, 1.0, 2.0 and 5.0 mg/5 g diet) to evaluate survival rates for 21 days. Thereafter, we evaluated markers of oxidative stress, antioxidant status and behavioral activity in D. melanogaster exposed to SB for seven (7) days. We observed that SB (2.0 and 5.0 mg/5 g diet) decreased the survival of D. melanogaster. Also, SB inhibited glutathione-S-transferase activity and depleted total thiols and nonprotein thiols contents. Moreover, SB (5 mg/5 g diet) increased nitric oxide (nitrite/nitrate) level and reduced flies' emergence rate. Conclusively, findings from this study revealed that exposure to high concentrations of SB reduced survival rate and induced toxicity via the induction of oxidative stress and inhibition of antioxidant enzymes in D. melanogaster.
Asunto(s)
Antioxidantes , Drosophila melanogaster , Animales , Drosophila melanogaster/metabolismo , Antioxidantes/farmacología , Benzoato de Sodio/toxicidad , Estrés Oxidativo , Compuestos de SulfhidriloRESUMEN
Epigenetics, specifically histone post-translational modification (HPTM) induced by environmental factors, plays a crucial role in the development of diabetes. Sodium benzoate (NAB) is a widely used additive, however, its potential contribution to diabetes has been largely overlooked. In 2018, a novel HPTM called benzoylation (Kbz) induced by NAB was discovered. This modification can be catalyzed by ACSS2 (acyl-CoA synthetase short-chain member 2) and acyltransferase P300/CBP, and can be reversed by erase enzymes SIRT2. Studies have indicated that Kbz may regulate insulin secretion, although the exact molecular mechanism remains unclear. In our study, C57BL/6J mice were divided into two groups: the NC group and the 1g/kg NAB water feeding group. In vivo experiments were conducted using ß-TC-6 cells, with 6 mM NAB or 100 µM benzoyl-CoA as stimuli, and 10 µM A485 (P300 inhibitor), 5 µM ACSS2 inhibitor (inhibiting benzoyl-CoA synthesis), or 5 µM AGK2 (SIRT2 inhibitor) as intervention factors. Our study found that, although the experimental concentration of NAB is below the maximum allowable concentration in food, it still damaged the insulin secretion function of C57BL/6J mice and induced inflammation and apoptosis of islet ß cells. We observed significant differences in serum benzoyl-CoA levels between healthy individuals and patients with type 2 diabetes. Furthermore, NAB concentration-dependently increases benzoyl-CoA and Kbz levels. When Kbz is down-regulated using A485 and ACSS2 inhibitor, we observed a reduction in ß cell inflammation, apoptosis, and insulin secretion damage. Conversely, up-regulating Kbz using AGK2 resulted in increased levels of ß cell inflammation and apoptosis. In conclusion, our data suggest that NAB, despite being within the safe dose range, may be an overlooked environmental risk factor contributing to the pathogenesis of diabetes through its impact on Kbz.
Asunto(s)
Diabetes Mellitus Tipo 2 , Benzoato de Sodio , Humanos , Ratones , Animales , Benzoato de Sodio/toxicidad , Benzoato de Sodio/metabolismo , Sirtuina 2/metabolismo , Diabetes Mellitus Tipo 2/inducido químicamente , Ratones Endogámicos C57BL , Histonas , Inflamación/inducido químicamente , ApoptosisRESUMEN
BACKGROUND: Liver damage is a global health concern associated with a high mortality rate. Sodium benzoate (SB) is a widely used preservative in the food industry with a wide range of applications. However, there's a lack of scientific reports on its effect on lipopolysaccharide-induced hepatic dysfunction. OBJECTIVE: The present study investigated the influence of SB on lipopolysaccharide (LPS)-induced liver injury. MATERIALS AND METHODS: Twenty-eight rats were randomly allocated into four groups: control (received distilled water), SB (received 600 mg/kg), LPS (received 0.25 mg/kg), and LPS + SB (received LPS, 0.25 mg/kg, and SB, 600 mg/kg). SB was administered orally for 14 days while LPS was administered intraperitoneally for 7 days. RESULTS: Administration of SB to rats with hepatocyte injury exacerbated liver damage with a significant increase in the activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). We also observed that SB aggravated LPS-mediated hepatic oxidative stress occasioned by a marked decrease in antioxidant status with a concomitant increase in lipid peroxidation. Furthermore, LPS - mediated increase in inflammatory biomarkers as well as histological deterioration in the liver was exacerbated following the administration of SB to rats. CONCLUSION: Taken together, the study provides experimental evidence that SB exacerbates hepatic oxidative stress and inflammation in LPS-mediated liver injury.
Asunto(s)
Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Enfermedad Hepática Inducida por Sustancias y Drogas , Ratas , Animales , Lipopolisacáridos/toxicidad , Benzoato de Sodio/toxicidad , Benzoato de Sodio/metabolismo , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/patología , Hígado , Inflamación/patología , Estrés Oxidativo , Enfermedad Hepática Inducida por Sustancias y Drogas/patologíaRESUMEN
Sodium benzoate is a widely used food and pharmaceutical preservative due to its antibacterial and antifungal activity. In the present study effect of different concentrations of sodium benzoate on hepatic antioxidants, inflammatory cytokines (TNF-α, IFN-γ, IL-1ß and IL-6), biochemical markers and histopathology of liver was evaluated. Twenty five adult rats (aged 1-2 months) with 5 rats per group were randomly distributed into 5 groups. Group 1 rats were used as control and all groups (1-5) were provided with water and fed ad libitum. In addition to usual water and food, rats of group 2, 3, 4 and 5 were treated with 70, 200, 400 and 700 mg/kg b.wt of sodium benzoate once a day via oral gavage for 30 days. Our results showed that activity of glutathione peroxidase (GPx), catalase (CAT), glutathione-s-transferase (GST), glutathione reductase (GR) and superoxide dismutase (SOD) in rats decreased significantly when treated with 200, 400 and 700 mg/kg b.wt of sodium benzoate. Increase in the concentration of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, serum total protein, albumin, globulin, urea and creatinine was found to be dose dependent. Severe histopathological damage was observed in the hepatic tissue at higher concentrations of sodium benzoate. It was noticed that high concentrations of sodium benzoate (200, 400 and 700 mg/kg b.wt) produce significant increase in inflammatory cytokine markers (TNF-α, IFN-γ, IL-1ß and IL-6) in comparison to control. Sodium benzoate at concentration of 70 mg/kg b.wt did not produce any significant changes in any of the above studied parameters.
Asunto(s)
Citocinas , Benzoato de Sodio , Animales , Antioxidantes/farmacología , Biomarcadores/metabolismo , Citocinas/metabolismo , Glutatión/metabolismo , Glutatión Transferasa/metabolismo , Interleucina-6 , Hígado , Masculino , Estrés Oxidativo , Ratas , Ratas Wistar , Benzoato de Sodio/toxicidad , Factor de Necrosis Tumoral alfa/metabolismo , AguaRESUMEN
The use of additives in different food products is growing up. It has attracted the attention towards the relation between the mutagenic potential of human diseases and food additives. Sunset yellow (SY) and sodium benzoate (NaB) are used as colorant and food additives worldwide. In the present study, genotoxic effects of different combinations of SY and NaB were assessed in vivo in female rats. Different combinations of SY and NaB were dissolved in water and administered daily to six animals groups for 12 weeks. Group 1 (control) received water, Group 2 received 5 mg/kg body weight (bw) SY plus 10 mg/kg bw NaB, group 3 received 5 mg/kg SY plus 100 mg/kg NaB, group 4 received 50 mg SY plus 100 mg/kg NaB, group 5 received 50 mg/kg SY plus 10 mg/kg NaB, group 6 received 200 mg/kg SY plus 750 mg/kg NaB, and group 7 received 20 mg/kg SY plus 75 mg/kg NaB. Genotoxicity investigations (Chromosomal aberration of bone marrow cells, Comet assay and DNA profile of liver cells) were carried out at the end of the experiment. Administration of 200 mg/kg SY plus 750 mg/kg NaB (group 6) induced the highest abnormalities percentage (1.5%) and showed structural abnormalities including end-to-end association, fragmentation, chromatid break, ring chromosome, and centric fusion break of chromosomes. Different combinations of SY and NaB induced an increase in the frequency of tailed nuclei (DNA damage) in liver cells. A concentration-dependent distinct DNA smear pattern was observed in the DNA isolated from liver cells of animals administered SY and NaB. In addition, administration of SY plus NaB resulted in an abnormal distribution of serum proteins. The results showed that the SY plus NaB could have genotoxic potential. With the increase applications of food additives, this study reported important data about screening the potential impacts.
Asunto(s)
Compuestos Azo/toxicidad , Daño del ADN , Colorantes de Alimentos/toxicidad , Conservantes de Alimentos/toxicidad , Benzoato de Sodio/toxicidad , Animales , Aberraciones Cromosómicas/inducido químicamente , Ensayo Cometa , Femenino , RatasRESUMEN
Sodium benzoate (SB) is a common food preservative. Its FDA described safety limit is 1000â¯ppm. Lately, increased use of SB has prompted investigations regarding its effects on biological systems. Data regarding toxicity of SB is divergent and controversial with studies reporting both harmful and beneficial effects. Therefore, we did a systematic dose dependent toxicity study of SB using zebrafish vertebrate animal model. We also investigated oxidative stress and anxiety-like behaviour in zebrafish larva treated with SB. Our results indicate that SB induced developmental (delayed hatching), morphological (pericardial edema, yolk sac edema and tail bending), biochemical (oxidative stress) and behavioural (anxiety-like behaviour) abnormalities in developing zebrafish larva. LC50 of SB induced toxicity was approximately 400â¯ppm after 48â¯h of SB exposure. Our study strongly supports its harmful effects on vertebrates at increasing doses. Thus, we suggest caution in the excessive use of this preservative in processed and convenience foods.
Asunto(s)
Conservantes de Alimentos/toxicidad , Larva/efectos de los fármacos , Benzoato de Sodio/toxicidad , Animales , Ansiedad/inducido químicamente , Conducta Animal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Conservantes de Alimentos/administración & dosificación , Glutatión Reductasa/genética , Lactoilglutatión Liasa/genética , Larva/crecimiento & desarrollo , Larva/fisiología , Modelos Animales , Estrés Oxidativo/efectos de los fármacos , Benzoato de Sodio/administración & dosificación , Regulación hacia Arriba/efectos de los fármacos , Pez Cebra/genética , Pez Cebra/crecimiento & desarrollo , Pez Cebra/fisiología , Proteínas de Pez Cebra/genéticaRESUMEN
Zebrafish (Danio rerio) is increasingly employed for evaluating toxicity and drug discovery assays. Commonly experimental approaches for biotoxicity assessment are based on visual inspection or video recording. However, these techniques are limited for large-scale assays, as they demand either a time-consuming detailed inspection of the animals or intensive computing resources in order to analyze a considerable amount of screenshots. Recently, we have developed a simple methodology for tracking the locomotor activity of small animals cultured in microtiter plates. In this work, we implemented this automatic methodology, based on infrared (IR) microbeam scattering, for measuring behavioral activity in zebrafish larvae. We determined the appropriate culture conditions, number of animals and stage of development to get robust results. Furthermore, we validated this methodology as a rapid test for evaluating toxicity. By measuring the effects of reference compounds on larvae activity, we were able to estimate the concentration that could cause a 50% decrease in activity events values (AEC50), showing a strong linear correlation (R² = 0.91) with the LC50 values obtained with the standard DarT test. The toxicity order of the measured compounds was CuSO4 > 2,4-dinitrophenol > 3,4-dichloroaniline > SDS > sodium benzoate > EDTA > K2CrO4 ; regarding solvents, EtOH ≈ DMSO. In this study, we demonstrate that global swimming behavior could be a simple readout for toxicity, easy to scale-up in automated experiments. This approach is potentially applicable for fast ecotoxicity assays and whole-organism high-throughput compound screening, reducing the time and money required to evaluate unknown samples and to identify leading pharmaceutical compounds.
Asunto(s)
Ecotoxicología/métodos , Actividad Motora/efectos de los fármacos , Dispersión de Radiación , Pruebas de Toxicidad , 2,4-Dinitrofenol/toxicidad , Compuestos de Anilina , Animales , Cromatos/toxicidad , Sulfato de Cobre/toxicidad , Relación Dosis-Respuesta a Droga , Ácido Edético/toxicidad , Femenino , Larva/efectos de los fármacos , Dosificación Letal Mediana , Masculino , Compuestos de Potasio/toxicidad , Reproducibilidad de los Resultados , Benzoato de Sodio/toxicidad , Dodecil Sulfato de Sodio/toxicidad , Pez CebraRESUMEN
The aim of this study was to evaluate the protective effect of catechin and quercetin in sodium benzoate- (SB-) induced oxidative stress in human erythrocytes in vitro. For this, the effects of SB (6.25, 12.5, 25, 50, and 100 µg/mL), catechin (10 µM), and quercetin (10 µM) on lipid peroxidation (LPO) and the activities of SOD, CAT, GPx, and GST were studied. Significantly higher LPO and lower activities of antioxidant enzymes were observed with the increasing concentrations of SB. Catechin or quercetin protected the erythrocytes against SB-induced toxicity only at low concentrations of SB. The presence of catechin or quercetin at 10 µM have no effect on SB-induced toxicity at high concentrations of SB (50 and 100 µg/mL). In conclusion, SB may cause oxidative stress as food additive in human erythrocytes in vitro. So, it appears that our findings provide evidence for the protection of erythrocytes from SB that could be considered for further studies.
Asunto(s)
Antioxidantes/farmacología , Catequina/farmacología , Eritrocitos/efectos de los fármacos , Peroxidación de Lípido , Quercetina/farmacología , Catalasa/metabolismo , Glutatión Peroxidasa/metabolismo , Glutatión Transferasa/metabolismo , Humanos , Benzoato de Sodio/toxicidad , Superóxido Dismutasa/metabolismoRESUMEN
OBJECTIVE: To investigate the behavioral characteristics, including anxiety and motor impairment, in sodium benzoate (NaB) treated rats. METHODS: The study was carried out between July and September 2012 in the Laboratory Animal Center of Shiraz University of Medical Sciences, Shiraz, Iran. The rats were divided into 2 groups receiving distilled water and NaB (200mg/kg/day). All the animals received daily gavages for 4 weeks. At the end of the fourth week, anxiety, and motor function were assessed in elevated plus maze and rotarod test. RESULTS: According to the results, NaB-treated rats spent less time in the open arm and had fewer entrances to the open arms in comparison with the control group (p<0.04). Also, the performance of the NaB-treated rats in fixed and accelerating speed rotarods was impaired, and the riding time (endurance) was lower than the control group (p<0.01). CONCLUSION: The performance of the NaB-treated rats was impaired in the elevated plus maze, an indicator of anxiety. Their riding time in fixed and accelerating speed rotarods was decreased, indicating motor impairment.
Asunto(s)
Ansiedad/inducido químicamente , Conservantes de Alimentos/toxicidad , Trastornos del Movimiento/etiología , Benzoato de Sodio/toxicidad , Animales , Modelos Animales de Enfermedad , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Prueba de Desempeño de Rotación con Aceleración ConstanteRESUMEN
The toxicity, in terms of changes in the DNA content, of two food preservatives, sodium nitrate and sodium benzoate was studied on the protozoan Tetrahymena pyriformis using DNA image analysis technology. For this purpose, selected doses of both food additives were administered for 2 h to protozoa cultures and DNA image analysis of T. pyriformis nuclei was performed. The analysis was based on the measurement of the Mean Optical Density which represents the cellular DNA content. The results have shown that after exposure of the protozoan cultures to doses equivalent to ADI, a statistically significant increase in the macronuclear DNA content compared to the unexposed control samples was observed. The observed increase in the macronuclear DNA content is indicative of the stimulation of the mitotic process and the observed increase in MOD, accompanied by a stimulation of the protozoan proliferation activity is in consistence with this assumption. Since alterations at the DNA level such as DNA content and uncontrolled mitogenic stimulation have been linked with chemical carcinogenesis, the results of the present study add information on the toxicogenomic profile of the selected chemicals and may potentially lead to reconsideration of the excessive use of nitrates aiming to protect public health.
Asunto(s)
Replicación del ADN/efectos de los fármacos , ADN Protozoario/efectos de los fármacos , Conservantes de Alimentos/toxicidad , Macronúcleo/efectos de los fármacos , Nitratos/toxicidad , Benzoato de Sodio/toxicidad , Tetrahymena pyriformis/efectos de los fármacos , ADN Protozoario/biosíntesis , Macronúcleo/metabolismo , Mitosis/efectos de los fármacos , Medición de Riesgo , Tetrahymena pyriformis/genética , Tetrahymena pyriformis/crecimiento & desarrolloRESUMEN
The synthetic food preservative sodium benzoate (SB) is widely used in both food and pharmaceutical industries. A growing body of evidence highlights the adverse effects of SB on human health; however, effect of the prolonged intake of SB on the reproductive system is not fully elucidated. The current study investigates the effect of different doses of SB (0-1000 mg/kg BW) on the reproductive system of male rats administered oral SB for 90 consecutive days. Results revealed that increasing doses of SB significantly altered the weight of reproductive organs, decreased sperm count and motility and enhanced the percentage of abnormal sperms. This was concomitant with significant decline in plasma testosterone and FSH levels, increase in plasma LH and decrease in the activities of 17ß-HSD and 17-KSR enzymes in the testes. Inflammation and oxidative stress were induced as indicated by the significant increase in TNF-α and IL-6 levels, inhibition of antioxidant enzymes activity and levels of GSH, increase in the levels of NO and TBARS and enhanced protein expression of mtTFA and UCP2 in the testes. Interestingly, p53 expression and caspase-3 activity were upregulated in the testes suggesting induction of apoptosis. Histopathological examination of the testes confirmed apoptosis and revealed degenerative alterations of the testes' architecture and perturbation of spermatogenesis. Based upon these findings, the no-observed-adverse-effect level of SB on the reproductive system was determined to be less than 1 mg/kg BW/day, highlighting the risks of long-term exposure to low as well as high doses of SB on male reproductive health.
Asunto(s)
Conservantes de Alimentos/toxicidad , Benzoato de Sodio/toxicidad , Administración Oral , Animales , Apoptosis/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Hormona Folículo Estimulante/sangre , Glutatión Transferasa/metabolismo , Inflamación/inducido químicamente , Inflamación/metabolismo , Inflamación/patología , Hormona Luteinizante/sangre , Masculino , Mitocondrias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Oxidorreductasas/metabolismo , Ratas Wistar , Reproducción/efectos de los fármacos , Recuento de Espermatozoides , Espermatozoides/efectos de los fármacos , Testículo/efectos de los fármacos , Testículo/metabolismo , Testículo/patología , Testosterona/sangreRESUMEN
BACKGROUND: Recent data have demonstrated that treatment with sodium benzoate (SB) leads to significant developmental defects in motor neuron axons and neuromuscular junctions in zebrafish larvae, thereby implying that SB can be neurotoxic. This study examined whether SB affects the development of dopaminergic neurons in the zebrafish brain. METHODS: Zebrafish embryos were exposed to different concentrations of SB for various durations, during which the survival rates were recorded, the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the neurons in the ventral diencephalon were detected by in situ hybridization and immunofluorescence, and the locomotor activity of larval zebrafish was measured. RESULTS: The survival rates were significantly decreased with the increase of duration and dose of SB-treatment. Compared to untreated clutch mates (untreated controls), treatment with SB significantly downregulated expression of TH and DAT in neurons in the ventral diencephalon of 3-day post-fertilization (dpf) zebrafish embryos in a dose-dependent manner. Furthermore, there was a marked decrease in locomotor activity in zebrafish larvae at 6dpf in response to SB treatment. CONCLUSIONS: The results suggest that SB exposure can cause significantly decreased survival rates of zebrafish embryos in a time- and dose-dependent manner and downregulated expression of TH and DAT in dopaminergic neurons in the zebrafish ventral diencephalon, which results in decreased locomotor activity of zebrafish larvae. This study may provide some important information for further elucidating the mechanism underlying SB-induced developmental neurotoxicity.
Asunto(s)
Diencéfalo/efectos de los fármacos , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/biosíntesis , Conservantes de Alimentos/toxicidad , Neuronas/efectos de los fármacos , Benzoato de Sodio/toxicidad , Tirosina 3-Monooxigenasa/biosíntesis , Proteínas de Pez Cebra/biosíntesis , Pez Cebra/embriología , Animales , Secuencia de Bases , ADN Complementario/genética , Diencéfalo/embriología , Diencéfalo/metabolismo , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo/efectos de los fármacos , Inducción Enzimática/efectos de los fármacos , Hibridación in Situ , Larva/efectos de los fármacos , Microscopía Fluorescente , Datos de Secuencia Molecular , Neuronas/metabolismo , Distribución Aleatoria , Natación , Tirosina 3-Monooxigenasa/genética , Proteínas de Pez Cebra/genéticaRESUMEN
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.
Asunto(s)
Conservantes de Alimentos/química , Albúmina Sérica/química , Citocinas/genética , Citocinas/metabolismo , Daño del ADN/efectos de los fármacos , Conservantes de Alimentos/toxicidad , Humanos , Estrés Oxidativo/efectos de los fármacos , Parabenos/química , Parabenos/toxicidad , Acetato de Sodio/química , Acetato de Sodio/toxicidad , Benzoato de Sodio/química , Benzoato de Sodio/toxicidad , Ácido Sórbico/química , Ácido Sórbico/toxicidadRESUMEN
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.
Asunto(s)
Aberraciones Cromosómicas/inducido químicamente , Conservantes de Alimentos/toxicidad , Linfocitos/efectos de los fármacos , Nitratos/toxicidad , Compuestos de Potasio/toxicidad , Benzoato de Sodio/toxicidad , Ácido Sórbico/toxicidad , Ciclo Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Humanos , Pruebas de MutagenicidadRESUMEN
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.
Asunto(s)
Exposición Dietética , Conservantes de Alimentos/análisis , Benzoato de Sodio/análisis , Ácido Sórbico/análisis , Cromatografía Líquida de Alta Presión , Estudios Transversales , Análisis de los Alimentos , Conservantes de Alimentos/toxicidad , Humanos , Irán , Límite de Detección , Política Nutricional , Medición de Riesgo , Benzoato de Sodio/toxicidad , Ácido Sórbico/toxicidad , Espectrofotometría UltravioletaRESUMEN
Sodium benzoate (SB) is a commonly used food preservative and anti-microbial agent in many foods from soup to cereals. However, little is known about the SB-induced toxicity and teratogenicity during early embryonic development. Here, we used zebrafish as a model to test the toxicity and teratogenicity because of their transparent eggs; therefore, the organogenesis of zebrafish embryos is easy to observe. After low dosages of SB (1-1000 ppm) treatment, the zebrafish embryos exhibited a 100% survival rate. As the exposure dosages increased, the survival rates decreased. No embryos survived after treatment with 2000 ppm SB. The 50% lethal dose (LD(50)) of zebrafish is found to be in the range of 1400-1500 ppm. Gut abnormalities, malformation of pronephros, defective hatching gland and edema in pericardial sac were observed after treatment with SB. Compared to untreated littermates (vehicle-treated control), SB-treated embryos exhibited significantly reduced tactile sensitivity frequencies of touch-induced movement (vehicle-treated control: 27.60+/-1.98 v.s. 1000 ppm SB: 7.89+/-5.28; N=30). Subtle changes are easily observed by staining with specific monoclonal antibodies F59, Znp1 and alpha6F to detect morphology changes in muscle fibers, motor axons and pronephros, respectively. Our data showed that the treatment of SB led to misalignment of muscle fibers, motor neuron innervations, excess acetyl-choline receptor cluster and defective pronephric tubes. On the basis of these observations, we suggest that sodium benzoate is able to induce neurotoxicity and nephrotoxicity of zebrafish larvae.
Asunto(s)
Anomalías Inducidas por Medicamentos/patología , Anomalías Inducidas por Medicamentos/psicología , Larva/anatomía & histología , Benzoato de Sodio/toxicidad , Teratógenos , Pez Cebra/fisiología , Animales , Anticuerpos Monoclonales , Relación Dosis-Respuesta a Droga , Embrión no Mamífero/efectos de los fármacos , Tracto Gastrointestinal/anomalías , Riñón/anomalías , Riñón/crecimiento & desarrollo , Actividad Motora/efectos de los fármacos , Neuronas Motoras/efectos de los fármacos , Neuronas Motoras/patología , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/patología , Unión Neuromuscular/anomalías , Unión Neuromuscular/patología , Fenotipo , Estimulación Física , Receptores Colinérgicos/efectos de los fármacos , Receptores Colinérgicos/genética , Factores de TiempoAsunto(s)
Perfumes/toxicidad , Benzoato de Sodio/toxicidad , Animales , Seguridad de Productos para el Consumidor , Femenino , Fertilidad/efectos de los fármacos , Humanos , Masculino , Ratones , Odorantes/análisis , Perfumes/química , Ratas , Ratas Sprague-Dawley , Sistema de Registros , Medición de Riesgo , Benzoato de Sodio/química , Pruebas de ToxicidadRESUMEN
Recently, the development of several gene expression-based prediction methods has been attempted in the fields of toxicology. CARCINOscreen® is a gene expression-based screening method to predict carcinogenicity of chemicals which target the liver with high accuracy. In this study, we investigated the applicability of the gene expression-based screening method to SD and Wistar rats by using CARCINOscreen®, originally developed with F344 rats, with two carcinogens, 2,4-diaminotoluen and thioacetamide, and two non-carcinogens, 2,6-diaminotoluen and sodium benzoate. After the 28-day repeated dose test was conducted with each chemical in SD and Wistar rats, microarray analysis was performed using total RNA extracted from each liver. Obtained gene expression data were applied to CARCINOscreen®. Predictive scores obtained by the CARCINOscreen® for known carcinogens were > 2 in all strains of rats, while non-carcinogens gave prediction scores below 0.5. These results suggested that the gene expression based screening method, CARCINOscreen®, can be applied to SD and Wistar rats, widely used strains in toxicological studies, by setting of an appropriate boundary line of prediction score to classify the chemicals into carcinogens and non-carcinogens.
Asunto(s)
Pruebas de Carcinogenicidad/métodos , Carcinógenos/toxicidad , Expresión Génica , Hígado/efectos de los fármacos , Fenilendiaminas/toxicidad , ARN/análisis , Benzoato de Sodio/toxicidad , Tioacetamida/toxicidad , Administración Oral , Animales , Carcinógenos/administración & dosificación , Hígado/metabolismo , Masculino , Análisis por Micromatrices , Fenilendiaminas/administración & dosificación , Valor Predictivo de las Pruebas , ARN/aislamiento & purificación , Ratas Sprague-Dawley , Ratas Wistar , Benzoato de Sodio/administración & dosificación , Tioacetamida/administración & dosificaciónRESUMEN
In this study, the genotoxic effects of sodium benzoate (SB) and potassium benzoate (PB) were investigated in cultured human peripheral lymphocytes using chromosomal aberrations (CA), sister chromatid exchange (SCE), and micronuclei (MN). The level of nuclear DNA damage of SB and PB were also evaluated using the comet assay. The lymphocytes were incubated with different concentrations of SB (6.25, 12.5, 25, 50, and 100 µg/ml) and PB (62.5, 125, 250, 500, and 1000 µg/ml). A significant increase was observed in CA, SCE, and MN, in almost all treatments compared to negative controls. SB and PB significantly decreased the mitotic index (MI) in all the treatments, compared to the negative controls. However, neither of the additives affected the replication index (RI). Although SB significantly increased DNA damage, PB did not cause a significant increase in DNA damage. The present results indicate that SB and PB are clastogenic, mutagenic and cytotoxic to human lymphocytes in vitro.