RESUMO
First in the literature this study aimed to investigate the effects of Tartrazine, a common industrial food dye, on kidney and whether Thymoquinone has a protective effect in tartrazine-induced nephrotoxicity. The study conducted on the rats bred at Inönü University Experimental Animals Production and Research Center. Wistar albino rats were randomly divided into 4 groups, where each group included 8 rats: control, Tartrazine, Thymoquinone, and Tartrazine + Thymoquinone groups. The experiments continued for 3 weeks and then, kidney tissues and blood samples were collected from the rats under anesthesia. Malondialdehyde (MDA), super oxidized dismutase (SOD), total oxidant status (TOS), increase in Oxidative stress index (OSI), glutathione (GSH), Glutathione peroxidase (GSH-Px), catalase (CAT), Total antioxidant status (TAS) levels decreased in the kidney tissues collected from the tartrazine group. Serum Bun and Creatinine levels increased in the tartrazine group. Tartrazine administration damaged and degenerated the glomeruli and cortical distal tubes in the histopathology of kidney tissues, also different degrees of inflammatory cell infiltration were observed in the renal cortex and medulla. Thymoquinone and tartrazine administration improved both biochemical and histopathological parameters. Tartrazine administration induced nephrotoxicity. This could be observed with the increase in oxidant capacity and the deterioration of kidney functions. Thymoquinone was observed to demonstrate strong antioxidant properties. Thymoquinone could be used primarily as a protective agent against Tartrazine-induced toxicity.
Assuntos
Antioxidantes , Benzoquinonas , Tartrazina , Animais , Humanos , Ratos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Benzoquinonas/farmacologia , Caspase 3/efeitos dos fármacos , Caspase 3/metabolismo , Glutationa/metabolismo , Rim/efeitos dos fármacos , Malondialdeído/metabolismo , Oxidantes/metabolismo , Oxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Superóxido Dismutase/metabolismo , Tartrazina/toxicidade , Tartrazina/metabolismoRESUMO
The use of additives, especially colorants, in food and pharmaceutical industry is increasing dramatically. Currently, additives are classified as contaminants of emerging concern (CECs). Concerns have been raised about the potential hazards of food additives to reproductive organs and fertility. The present study investigates the reproductive toxicity of tartrazine (TRZ), a synthetic colorant, in male rats and aims to explore the curative effect of Ginkgo biloba extract (EGb) against TRZ-induced testicular toxicity. Twenty-four rats were divided into four groups: the control (0.5 ml distilled water), the EGb group (100 mg/kg EGb alone), the TRZ group (7.5 mg/kg TRZ alone), and the TRZ-EGb group (7.5 mg/kg TRZ plus 100 mg/kg EGb). The doses were administered orally in distilled water once daily for 28 days. Toxicity studies of TRZ investigated testicular redox state, serum gonadotropins, and testosterone levels, testicular 17 ß-hydroxysteroid dehydrogenase activity, sperm count and quality, levels of inflammatory cytokines, and caspase-3 expression as an apoptotic marker. Also, histopathological alterations of the testes were examined. TRZ significantly affected the testicular redox status as indicated by the increase in malondialdehyde and the decrease in reduced glutathione, superoxide dismutase, and catalase. It also disrupted serum gonadotropins (follicle stimulating hormone and luteinizing hormone) and testosterone levels and the activity of testicular 17ß-hydroxysteroid dehydrogenase. Additionally, TRZ adversely affected sperm count, motility, viability, and abnormality. Levels of tumor necrosis factor-α, interleukin-1ß, interleukin-6, and expression of caspase-3 were increased in the testes. Histopathological examination of the testes supported the alterations mentioned above. Administration of EGb significantly ameliorated TRZ-induced testicular toxicity in rats. In conclusion, EGb protected against TRZ-induced testicular toxicity through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms.
Assuntos
Antioxidantes , Extrato de Ginkgo , Testículo , Ratos , Masculino , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Caspase 3/metabolismo , Tartrazina/toxicidade , Estresse Oxidativo , Ginkgo biloba , Extratos Vegetais/metabolismo , Hormônio Luteinizante , Anti-Inflamatórios/farmacologia , Testosterona , Hidroxiesteroide Desidrogenases/metabolismo , Hidroxiesteroide Desidrogenases/farmacologia , Água/metabolismo , SementesRESUMO
Tartrazine (E-102) is one of the most widely used artificial food azo-colors that can be metabolized to highly sensitizing aromatic amines such as sulphanilic acid. These metabolites are oxidized to N-hydroxy derivatives that cause neurotoxicity. Melatonin is a neurohormone. That possesses a free-radical scavenging effect. The present work was mainly designed to evaluate the possible ameliorative role of melatonin against tartrazine induced neurotoxicity in cerebral cortex and cerebellum of male rats. Adult male rats were administered orally with tartrazine (7.5 mg/kg) with or without melatonin (10 mg/kg) daily for four weeks. The data revealed that tartrazine induced redox disruptions as measured by significant (p < 0.05) increased malondialdehyde (MDA) level and inhibition of (GSH) concentration and catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) antioxidant enzyme activities. Besides, brain acetyl cholin (Ach) and gamma-aminobutyric acid (GABA) were elevated while, dopamine (DA) was depleted in trtrazine -treated rats. Moreover, tartrazine caused a significant (p < 0.05) increase in the brain interleukin-6 (IL-6), interleukin-1ß (IL-1 ß) and tumor necrosis factor-α (TNFα). At the tissue level, tartrazine caused severe histopathological changes in the cerebellum and cerebral cortex of rats. The immunohistochemical results elucidated strong positive expression for Caspase-3 and GFAP and weak immune reaction for BcL2 and synaptophysin in tatrazine- treated rats. The administration of melatonin to tartrazine -administered rats remarkably alleviated all the aforementioned tartrzine-induced effects. It could be concluded that, melatonin has a potent ameliorative effect against tartrazine induced neurotoxicity via the attenuation of oxidative/antioxidative responses.
Assuntos
Melatonina , Tartrazina , Ratos , Masculino , Animais , Tartrazina/toxicidade , Melatonina/farmacologia , Ratos Wistar , Estresse Oxidativo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Catalase/metabolismo , Superóxido Dismutase/metabolismo , Malondialdeído/metabolismo , Glutationa Peroxidase/metabolismoRESUMO
BACKGROUND: Among the food additives used in the food industry, food dyes are considered the most toxic. For instance, tartrazine (TRZ) is a food colorant commercially available with conflicting data regarding its cytotoxic, genotoxic, and mutagenic effects. Therefore, this study aimed to evaluate the cytotoxic and mutagenic potential of TRZ using different eukaryotic cells (in vitro). METHODS: This study employed 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), brine shrimp lethality, Allium cepa and Saccharomyces cerevisiae tests. Different concentrations of TRZ and different exposure times were used in this study. RESULTS: The results demonstrate that TRZ induced a concentration-dependent toxic effect on the test systems. It also exerted cytotoxicity in fibroblasts and human gastric cells. In addition, TRZ showed mutagenic effects on the A. cepa test system. However, its toxicogenic effects may not relate to the oxidizing activity, which was confirmed by the S. cerevisiae test model. CONCLUSION: Taken together, TRZ exerted toxicogenic effects on the test systems. Therefore, it may be harmful to health, especially its prolonged use may trigger carcinogenesis.
Assuntos
Mutagênicos , Tartrazina , Humanos , Tartrazina/toxicidade , Mutagênicos/toxicidade , Aditivos Alimentares/toxicidade , Células Eucarióticas , Saccharomyces cerevisiae/genéticaRESUMO
Azo-dyes such as Allura Red, Carmoisine, Amaranth, Sunset Yellow (SY), Brilliant Blue, Tartrazine (Tz), etc., are popular as food coloring agents due to their low cost and stability. SY and Tz are the most used members of this group of dyes since they have similar colors and are usually used together in food products. Despite their advantageous industrial use, they exhibit a risk toxicity profile with adverse effects such as allergy, asthma, carcinogenicity, genotoxicity, cytotoxicity, anxiety, etc. Therefore, the United States Food and Drug Administration (FDA) and European Food Safety Authority (EFSA) regulate the permissions for using these compounds to provide safe food products for consumers and prevent adverse effects both short and long-term. Considering all of these, for the analysis of azo toxic dyes, highly sensitive, low-cost, simple, and rapid sensors are necessary. Electrochemical nanosensors, which combine the unique features of electrochemistry and nanotechnology, are devices with all these advantages and are widely used for the determination of azo dyes. SY and Tz step forth as the most used food dyes in the class of azo-toxic dyes. They are often preferred together in food products, increasing the occurrence and exposure risk. Therefore, the analysis of Sunset Yellow and Tartrazine in food products has significant importance. In this review, the latest nanomaterial-based approaches for the electrochemical sensors on the analysis of SY and Tz in food samples were evaluated in terms of used nanomaterials and applied food samples.
Assuntos
Compostos Azo/toxicidade , Técnicas Eletroquímicas/métodos , Contaminação de Alimentos/análise , Tartrazina/química , Compostos Azo/química , Análise de Alimentos/métodos , Tartrazina/toxicidadeRESUMO
Bile acid accumulation and subsequent liver damage is a frequent adverse effect induced by drugs. Considerable efforts have therefore been focused on the introduction and characterization of tools that allow reliable prediction of this type of drug-induced liver injury. Among those are the cholestatic index and transcriptomic profiling, which are typically assessed in in vitro settings. The present study was set up to test the applicability of both tools to non-pharmaceutical compounds with cholestatic potential, including the industrial compound bis(2-ethylhexyl)phthalate, the cosmetic ingredients triclosan and octynoic acid, the herbicides paraquat and quizalofop-para-ethyl, and the food additives sunset yellow and tartrazine, in a human hepatoma cell culture model of cholestatic liver injury. The cholestatic index method showed cholestatic liability of sunset yellow, tartrazine and triclosan. Of those, tartrazine induced transcriptional changes reminiscent of the transcriptional profile of cholestatic drugs. Furthermore, a number of genes were found to be uniquely modulated by tartrazine, in accordance with the cholestatic drugs atazanavir, cyclosporin A and nefazodone, which may have potential as novel transcriptomic biomarkers of chemical-induced cholestatic liver injury. In conclusion, unambiguous identification of the non-pharmaceutical compounds tested in this study as inducers of cholestasis could not be achieved.
Assuntos
Compostos Azo/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Colestase/induzido quimicamente , Tartrazina/toxicidade , Triclosan/toxicidade , Linhagem Celular Tumoral , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Colestase/complicações , Expressão Gênica/efeitos dos fármacos , Humanos , Transcriptoma/efeitos dos fármacosRESUMO
Phytoestrogens have been widely praised for their health-promoting effects, whereas synthetic environmental estrogens are considered a toxicological risk to human health. The aim of this study was therefore to compare in vitro the estrogenic, cytotoxic, and genotoxic profiles of three common estrogen-like endocrine-disrupting chemicals: the phytoestrogens 8-prenylnaringenine (8-PN) and genistein and the synthetic xenoestrogen tartrazine. As assessed by a yeast bioreporter assay and estrogen-dependent proliferative response in human mammary gland adenocarcinoma cell line (MCF-7), 8-PN showed the highest estrogen-like activity of the three compounds, followed by tartrazine and genistein. After 24-h incubation on MCF-7 cells, all three compounds exhibited low cytotoxicity in the lactate dehydrogenase assay and no genotoxicity in the micronucleus assay. These results demonstrate that 8-PN, genistein and tartrazine possess variable estrogenic activity but display little cellular toxicity in short-term tests in vitro. No difference between phytoestrogens and a synthetic xenoestrogen could be established.
Assuntos
Genisteína , Tartrazina , Dano ao DNA , Estrogênios , Genisteína/toxicidade , Humanos , Fitoestrógenos/toxicidade , Tartrazina/toxicidadeRESUMO
Twenty-five male Wistar rats (140-170 g) were partitioned into 5 groups (n = 5). 2.5 mg/kg, 5 mg/kg, 10 mg/kg and 20 mg/kg of combine Tartrazine and Erythrosine (T+E; 50:50) were administered for 23 days. Serum urea and creatinine, gene expression and profiling of pro-inflammatory cytokine (Tumor Necrosis Factor- α gene), Caspase-9 and Kidney injury molecule-1 (KIM-1) and histomorphological examination of the kidney were investigated. The fold change of relative gene expression of TNF-α gene showed significantly (p < 0.05) up-regulation in all the treated rats except for the 10 mg/kg T+E treated rats when compared to control rats. Casp-9 and KIM-1 genes were significantly (p < 0.05) up-regulated in low dose treatment (2.5 mg/kg T+E and 5 mg/kg T+E) and down-regulated in high dose treatment (10 mg/kg T+E and 20 mg/kg T+E). However, there was significant (p < 0.05) increase in serum urea concentration in the rats treated with 5 mg/kg T+E and 20 mg/kg T+E while the rats treated with 10 mg/kg T+E indicated a significant (p < 0.05) decrease. Conversely, serum creatinine concentration indicated significant (p < 0.05) increase in10mg/kg T+E and 20 mg/kg T+E treated rats versus the control. From the histomorphological examination of the kidney, there was hypertrophy of the glomeruli in relation to the size of Bowman's capsule in the 10 mg/kg T+E and 20 mg/kg T+E treated rats. Kidney function was impaired as evident in up-regulation of TNF-α gene, KIM-1 gene, and serum urea and creatinine concentration with down-regulation of Casp-9 gene. The combined treatment also tampers with the architecture of the kidney.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Caspase 9/metabolismo , Moléculas de Adesão Celular/metabolismo , Corantes/toxicidade , Eritrosina/toxicidade , Rim/efeitos dos fármacos , Tartrazina/toxicidade , Fator de Necrose Tumoral alfa/metabolismo , Injúria Renal Aguda/enzimologia , Injúria Renal Aguda/genética , Injúria Renal Aguda/patologia , Animais , Caspase 9/genética , Moléculas de Adesão Celular/genética , Creatinina/sangue , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica , Rim/enzimologia , Rim/patologia , Masculino , Ratos Wistar , Fator de Necrose Tumoral alfa/genética , Ureia/sangueRESUMO
The present study evaluates the regulatory effect of Nano-Curcumin (Nano-CUR) against tartrazine (TZ)-induced injuries on apoptosis-related gene expression (i.e., p53, CASP-3 and CASP-9), antioxidant status, and DNA damages in bone marrow in treated rats. Male rats were arbitrarily separated into five groups, and each group was comprised of 10 rats each. The 1st group served as control (G1). The 2nd group ingested 7.5 mg TZ/kg. b.w. (body weight). The 3rd group ingested Nano-CUR 1 g/kg b.w. The 4th and 5th groups were respectively administered with (1 g Nano-CUR + 7.5 mg TZ/kg. b.w.) and (2 g Nano-CUR + 7.5 mg TZ/kg. b.w.). At the end of the experiment, blood samples, livers, and kidneys were collected. Livers and kidneys were homogenized and used for the analysis of reduced glutathione, malonaldhyde, total antioxidant capacity, lipid peroxide antioxidant enzyme activities, apoptosis-related gene expression, and genotoxicity by comit test. The ingestion of TZ for 50 days resulted in significant decreases in body, and kidney weights in rats and a relative increase in the liver weight compared to control. In contrast, the ingestion of Nano-CUR with TZ remarkably upgraded the body weight and relative liver weight compared to the normal range in the control. Aditionally, TZ ingestion in rats increased the oxidative stress biomarkers lipid peroxide (LPO) and malonaldehyde (MDA) significantly, whereas it decreased the reduced glutathione (GSH) levels and total antioxidant capacity (TAC). Similarly, the levels of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) significantly deteriorated in response to TZ ingestion. Moreover, the results revealed a remarkable up-regulation in the level of expression for the three examined genes, including p53, CASP-3, and CASP-9 in TZ-ingested rats compared to the control. On the other hand, the comet assay result indicates that the ingestion of TZ induced DNA damage in bone marrow. Notably, the administration of Nano-CUR protected the kidney and liver of TZ-ingested rats as evidenced by a significant elevation in all antioxidant activities of tested enzymes (i.e, SOD, GPx, and CAT), vital recovery in GSH and TAC levels, and a statistical decrease in LPO and MDA compared to TZ-ingested rats. Interestingly, the ingestion of rats with TZ modulates the observed up-regulation in the level of expression for the chosen genes, indicating the interfering role in the signaling transduction process of TZ-mediated poisoning. The results indicate that the administration of Nano-CUR may protect against TZ-induced DNA damage in bone marrow. According to the results, Nano-CUR exerted a potential protective effect against oxidative stress, DNA damage, and the up-regulation of apoptosis-related genes induced by TZ ingested to rats.
Assuntos
Curcumina/administração & dosagem , Nanopartículas/administração & dosagem , Tartrazina/toxicidade , Animais , Antioxidantes/administração & dosagem , Antioxidantes/química , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/genética , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Curcumina/química , Dano ao DNA , Corantes de Alimentos/administração & dosagem , Corantes de Alimentos/química , Corantes de Alimentos/toxicidade , Expressão Gênica/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Testes de Mutagenicidade , Mutagênicos/toxicidade , Nanopartículas/química , Nanopartículas/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , SolubilidadeRESUMO
AIM: To investigate the effects of tartrazine exposure on neural tube development, in early stage chicken embryos. MATERIAL AND METHODS: A total of 120 fertilized specific pathogen-free chicken eggs were divided into 4 equal groups (groups 1?4). After 30 hours of incubation, the eggs, except for the Group 1 (control group), were opened under 4X optical magnification. Group 2 was administered physiological saline. Group 3 was administered a middle dose of tartrazin (4.5 mg/kg) at a volume of 20 µL by the in ovo method, and group 4 was administered a high dose of tartrazine (7.5 mg/kg) using the same process. Incubation was continued until the end of the 72nd hour; all embryos were then removed from the eggs and histopathologically examined. RESULTS: Of the 120 embryos incubated, normal development and the closed neural tubes were shown in all embryos in group 1; 23 in group 2; 19 in group 3 and; only 9 in group 4. Open neural tubes were found in; 4 embryos in group 2; 5 embryos in group 3 and; 13 embryos in group 4. The neural tube closure defect was found to be significantly higher in group 4 compared to the other groups (p < 0.01). CONCLUSION: Based on our data, tartrazine, as one of the widely used food coloring agent, was seen to cause a neural tube defect in the chicken embryo model.
Assuntos
Corantes de Alimentos/toxicidade , Defeitos do Tubo Neural/induzido quimicamente , Defeitos do Tubo Neural/patologia , Tubo Neural/efeitos dos fármacos , Tartrazina/toxicidade , Animais , Embrião de Galinha , Galinhas , Desenvolvimento Embrionário/efeitos dos fármacos , Desenvolvimento Embrionário/fisiologia , Tubo Neural/patologiaRESUMO
Honey is traditionally used in burns, wound healing, ulcers, boils, and fistulas. Honey was tested to prevent tartrazine toxicity in male rats for 8 weeks. The 18 rats of the experiment were randomly divided into three 6-rat groups. The negative control group (G1) fed diet with sulfanilic acid, the tartrazine positive group (G2) fed diet containing tartrazine and sulfanilic acid and the honey-treated group (G3) fed diet as in G2 and cotreated with honey. Tartrazine decreased antioxidants, high-density lipoproteins and proteins, and increased liver enzymes, kidney indices, lipid peroxidation, triglycerides, total cholesterol, and low- and very-low-density lipoproteins. In addition, tartrazine-treated group showed drastic damage of the tissues of stomach, liver, kidney, and testis. Honey treatment increased antioxidants and high-density lipoproteins, and decreased lipid peroxidation, liver enzyme and kidney parameters. Honey treatment also improved stomach, liver, kidney, and testis tissues. In conclusion, honey protects male rats against tartrazine toxicity. PRACTICAL APPLICATIONS: Honey was tested to prevent tartrazine toxicity in male rats in an experiment conducted for 8 weeks. Catalase, glutathione reductase, superoxide dismutase, glutathione reduced, the low- and high-density lipoproteins, lipid peroxidation, liver enzyme, and kidney parameters were measured to evaluate both the toxic effect of tartrazine in G2 and the protective potential of honey in G3.
Assuntos
Corantes de Alimentos/toxicidade , Mel/análise , Substâncias Protetoras/administração & dosagem , Tartrazina/toxicidade , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Corantes de Alimentos/administração & dosagem , Glutationa/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Superóxido Dismutase/metabolismo , Tartrazina/administração & dosagem , Testículo/efeitos dos fármacos , Testículo/metabolismoRESUMO
Tartrazine, an azo dye used in food, cosmetics, and pharmaceuticals with the effects on cell cycle, is not well understood. Therefore, we investigated the toxicity of tartrazine in rat brain with high-dose aspirin. Male Wistar rats (n = 24) were divided into (C) control, (T) tartrazine (700 mg/kg body weight [BW] at weeks 1 and 2), (A) aspirin (150 mg/kg [BW] at weeks 1, 2, and 3), and (TA) aspirin + tartrazine (150 mg/kg [BW] aspirin at weeks 1, 2, and 3 and 700 mg/kg [BW] tartrazine at weeks 1 and 2) groups. The expression of p53, B cell lymphoma-2 extra-large (Bcl-xL), cyclin-dependent kinase 2 (CDK2), p27, and Ki67 was evaluated by quantitative reverse-transcription PCR. A histopathological analysis of brain tissue and oxidative stress level was assessed based on reduced glutathione (GSH), ascorbic acid (AA), and malondialdehyde levels. We found that Bcl-xL, Ki67, CDK2, and p27 were upregulated and p53 was downregulated in the tartrazine-treated group as compared to the control group. Aspirin administration reversed these changes except P53 expression. Tartrazine had no effect on lipid peroxidation but altered AA and GSH levels with no reversal by aspirin treatment. Histopathological analysis revealed that aspirin prevented tartrazine-induced damage including increased perivascular space and hemorrhage. These results indicate that aspirin protects the brain from tartrazine-induced toxicity independent of p53 signaling and antioxidant mechanisms.
Assuntos
Aspirina/administração & dosagem , Ciclo Celular/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética , Animais , Antioxidantes/administração & dosagem , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Quinase 2 Dependente de Ciclina/genética , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica , Glutationa/genética , Humanos , Antígeno Ki-67/genética , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Tartrazina/toxicidade , Proteína bcl-X/genéticaRESUMO
Tartrazine is one of the most widely used food additives. The present investigation was carried out on 40 adult male albino rats. They were divided into four groups of ten animals for each. Group I was considered as a control group. Group II was treated with tartrazine daily in a dose 7.5 mg/kg body weight by oral gavage for 30 days. Group III was received 15 mg/kg body weight of tartrazine for the same period. Group IV was administered tartrazine in a dose 100 mg/kg body weight for the whole duration of the experiment. At the end of experiment, samples from the cerebellum, submandibular salivary glands, and kidneys were fixed in neutral buffered formalin 10% and prepared routinely for paraffin sectioning and staining for histopathological and immunohistochemical investigations of proliferating cell nuclear antigen "PCNA" and glial fibrillar acidic protein "GFAP". Tartrazine-treated groups revealed histopathological degenerative changes in the obtained organs. In group II, the cerebellum showed subcortical edema, congestion of the blood vessels, cytoplasmic vacuolations, and pyknosis of the nuclei in the gray matter neurons. Concerning the submandibular glands, they expressed cytoplasmic vacuolations and pyknosis of the nuclei of the acinar cells, congestion of the interacinar blood capillaries, and degenerative changes in the striated duct. The kidneys appeared with interstitial hemorrhage and dilatation of the glomerular capillaries. The PCT and DCT showed ill-defined cell boundaries. The collecting tubules in the renal medulla appeared with flattened epithelial cells. The severity of these changes increases by increasing the dose of tartrazine in group III and reach to the highest level in group IV. The immunoexpression of the GFAP in the cerebellum of the experimental groups was intense compared to the control group. The immunoreactivity of PCNA in the nuclei of the acinar and ductal cells of the submandibular gland and the cells of the renal cortex and medulla was strong in the tartrazine-treated groups compared to the control group. The current study concluded that the tartrazine had serious effect on the cerebellum, submandibular glands, and kidneys that adversely affect the functions of these organs.
Assuntos
Corantes/toxicidade , Tartrazina/toxicidade , Animais , Cerebelo/efeitos dos fármacos , Células Epiteliais , Rim/efeitos dos fármacos , Masculino , Ratos , Glândula Submandibular/efeitos dos fármacos , Testes de ToxicidadeRESUMO
Food Yellow 4 (FY4) is a lemon-yellow-colored synthetic organic azo dye, which is used widely for imparting pleasant and attractive appearance to foods and cosmetics. The present study aimed at evaluating the possible mechanism underlying the FY4-induced reprotoxicity in rats, and the potential supportive role of royal jelly (RJ) or cod liver oil (CLO), which is a natural remedy with several pharmacological benefits, against induced toxicity. Forty-eight male rats were divided into different groups-the control group, the CLO group (0.4â¯mL/kg), the RJ group (300â¯mg/kg), the FY4 group (500â¯mg/kg b.w.), and the co-treated groups (FY4â¯+ CLO or FY4â¯+ RJ). Semen analysis, serum hormones, and enzyme activities were estimated. Immunohistochemical staining was performed using anti-PCNA, anti-Sox 9, anti-STRA8, anti-DMC1, and anti-ssDNA antibody. The FY4 group exhibited a significant decrease in sperm concentration and motility percentage (%) and a substantial reduction in the TES and LH levels. Testicular LDH, ACP, and SDH were observed to be inhibited. Furthermore, co-localization of DMC1 and ssDNA, which reflected apoptotic induction in the leptotene and zygotene spermatocytes, respectively, was observed to have markedly elevated in the FY4 treated rats, with fewer PCNA-positive and SOX9-positive cells and higher ssDNA-positive cells in the seminiferous epithelium in comparison to the control groups. Interestingly, co-treatment with CLO or RJ exhibited healthy sperms and restored their features, activated the enzyme production, and raised the levels of sexual hormones. In addition, both RJ and CLO restored the features of the testicular tissue as observed under a light microscope, and limited the apoptosis as observed through antibody staining. Collectively, the results of the present study revealed that the co-administration of RJ or CLO with FY4 improved the biochemical, hormonal, and structural aspects of the testicular tissue in rats. Therefore, CLO and RJ may be considered promising agents that would be able to improve the testicular structure and function in the FY4-exposed individuals.
Assuntos
Apoptose/efeitos dos fármacos , Óleo de Fígado de Bacalhau/farmacologia , Ácidos Graxos/farmacologia , Corantes de Alimentos/toxicidade , Recombinases/metabolismo , Tartrazina/toxicidade , Testículo/efeitos dos fármacos , Animais , Alimentos , Masculino , Ratos , Ratos Wistar , Reprodução/efeitos dos fármacos , Contagem de Espermatozoides , Espermatozoides , Testículo/enzimologia , Testículo/patologiaRESUMO
Tartrazine is a food colour that activates the transcriptional function of the human oestrogen receptor alpha in an in vitro cell model. Since oestrogens are cholestatic, we hypothesised tartrazine will cause periportal injury to the liver in vivo. To test this hypothesis, tartrazine was initially administered systemically to mice resulting in a periportal recruitment of inflammatory cells, increased serum alkaline phosphatase activity and mild periportal fibrosis. To determine whether an oestrogenic effect may be a key event in this response, tartrazine, sulphonated metabolites and a food additive contaminant were screened for their ability to interact with murine oestrogen receptors. In all cases, there were no interactions as agonists or antagonists and further, no oestrogenicity was observed with tartrazine in an in vivo uterine growth assay. To examine the relevance of the hepatic effects of tartrazine to its use as a food additive, tartrazine was orally administered to transgenic NF-κB-Luc mice. Pre- and concurrent oral treatment with alcohol was incorporated given its potential to promote gut permeability and hepatic inflammation. Tartrazine alone induced NF- κB activities in the colon and liver but there was no periportal recruitment of inflammatory cells or fibrosis. Tartrazine, its sulphonated metabolites and the contaminant inhibited sulphotransferase activities in murine hepatic S9 extracts. Given the role of sulfotransferases in bile acid excretion, the initiating event giving rise to periportal inflammation and subsequent hepatic pathology through systemic tartrazine exposure is therefore potentially associated an inhibition of bile acid sulphation and excretion and not on oestrogen receptor-mediated transcriptional function. However, these effects were restricted to systemic exposures to tartrazine and did not occur to any significant effect after oral exposure.
Assuntos
Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Corantes de Alimentos/toxicidade , Fígado/efeitos dos fármacos , Tartrazina/toxicidade , Administração Oral , Animais , Linhagem Celular , Estradiol/farmacologia , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Etanol/toxicidade , Feminino , Injeções Intraperitoneais , Fígado/metabolismo , Testes de Função Hepática , Luciferases de Vaga-Lume/genética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , NF-kappa B/genéticaRESUMO
This study is aimed to evaluate the possible neurotoxic effect of tartrazine (T), an extensively used synthetic azo dye, as well as to determine the potential modulatory role of cod liver oil (CLO) or royal jelly (RJ) against such effects. For this purpose, thirty-six male rat pups were allocated into six groups. The 1st group received distilled water (control group), the 2nd group was given 300 mg RJ/kg bw (RJ group), the 3rd group was given 0.4 ml CLO/kg bw (CLO group), the 4th was given 500 mg T/kg bw (T group). The 5th group was given T concurrently with RJ (TRJ group) and the 6th group was given T concurrently with CLO (TCLO group), at the same doses as the former groups. All treatments were given orally for 30 consecutive days. The concentrations of different brain neurotransmitters, gamma amino butyric acid (GABA), dopamine (DA) and serotonin (5HT) as well as the antioxidant and oxidative stress biomarkers were measured in the brain homogenates. An immunohistochemical staining of the cerebral cortex was applied with the anti-ssDNA antibody (an apoptotic cell marker) to reveal the changes in brain structure. The T group revealed a significant decrease in the concentration of the brain neurotransmitters, a sharp shortage in the level of antioxidant biomarkers (super oxide dismutase, catalase and the reduced glutathione), a marked increase in malondialdehyde levels, and numerous apoptotic cells in the brain cortex compared with the other groups. Interestingly, all the previously mentioned parameters were almost retrieved in both the TRJ and TCLO groups compared to the T group. These results conclusively demonstrate that RJ and CLO administration provides sufficient protection against the ruinous effects of T on rat pups brain tissue function and structure.
Assuntos
Encéfalo/efeitos dos fármacos , Óleo de Fígado de Bacalhau/farmacologia , Ácidos Graxos/farmacologia , Tartrazina/toxicidade , Animais , Masculino , RatosRESUMO
Tartrazine is a food additive that belongs to a class of artificial dyes and contains an azo group. Studies about its genotoxic, cytotoxic and mutagenic effects are controversial and, in some cases, unsatisfactory. This work evaluated the potential in vitro cytotoxicity, genotoxicity and effects on DNA repair of human lymphocytes exposed to the dye. We assessed the cytotoxicity of tartrazine by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide test and the response of DNA repair through comet assay (alkaline version). We used different concentrations of the dye, ranging from 0.25-64.0 mM. The results demonstrated that tartrazine has no cytotoxic effects. However, this dye had a significant genotoxic effect at all concentrations tested. Although most of the damage was amenable to repair, some damage remained higher than positive control after 24 h of repair. These data demonstrate that tartrazine may be harmful to health and its prolonged use could trigger carcinogenesis.
Assuntos
Reparo do DNA/efeitos dos fármacos , Corantes de Alimentos/toxicidade , Linfócitos/efeitos dos fármacos , Tartrazina/toxicidade , Adolescente , Adulto , Células Cultivadas , Ensaio Cometa , Dano ao DNA , Feminino , Humanos , MasculinoRESUMO
Primary biliary cirrhosis (PBC) is a cholestatic liver disease of unknown cause that occurs most frequently in post-menopausal women. Since the female sex hormone oestrogen can be cholestatic, we hypothesised that PBC may be triggered in part by chronic exposure to xenoestrogens (which may be more active on a background of low endogenous oestrogen levels seen in post-menopausal women). A reporter gene construct employing a synthetic oestrogen response element predicted to specifically interact with oestrogen receptors (ER) was constructed. Co-transfection of this reporter into an ER null cell line with a variety of nuclear receptor expression constructs indicated that the reporter gene was trans-activated by ERα and ERß, but not by the androgen, thyroid, progesterone, glucocorticoid or vitamin D receptors. Chemicals linked to PBC were then screened for xenoestrogen activity in the human ERα-positive MCF-7 breast cancer cell line. Using this assay, the coal-derived food and cosmetic colourings--sunset yellow and tartrazine--were identified as novel human ERα activators, activating the human ER with an EC(50%) concentration of 220 and 160 nM, respectively.
Assuntos
Compostos Azo/toxicidade , Corantes/toxicidade , Receptor alfa de Estrogênio/metabolismo , Testes Genéticos , Tartrazina/toxicidade , Transcrição Gênica/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Receptor alfa de Estrogênio/agonistas , Feminino , Testes Genéticos/métodos , Humanos , Cirrose Hepática Biliar/induzido quimicamente , Cirrose Hepática Biliar/metabolismo , Transcrição Gênica/fisiologia , Xenobióticos/toxicidadeRESUMO
The synthetic food dyes studied were rose bengal (RB), phroxine (PL), amaranth, erythrosine B (ET), allura red, new coccine, acid red (AR), tartrazine, sunset yellow FCF, brilliant blue FCF, and indigo carmine. First, data confirmed that these dyes were not substrates for CYP2A6, UGT1A6, and UGT2B7. ET inhibited UGT1A6 (glucuronidation of p-nitrophenol) and UGT2B7 (glucuronidation of androsterone). We showed the inhibitory effect of xanthene dye on human UGT1A6 activity. Basic ET, PL, and RB in those food dyes strongly inhibited UGT1A6 activity, with IC(50) values = 0.05, 0.04, and 0.015 mM, respectively. Meanwhile, AR of an acidic xanthene food dye showed no inhibition. Next, we studied the inhibition of CYP3A4 of a major phase I drug-metabolizing enzyme and P-glycoprotein of a major transporter by synthetic food dyes. Human CYP3A4 and P-glycoprotein were also inhibited by basic xanthene food dyes. The IC(50) values of these dyes to inhibit CYP3A4 and P-glycoprotein were the same as the inhibition level of UGT1A6 by three halogenated xanthene food dyes (ET, PL, and RB) described above, except AR, like the results with UGT1A6 and UGT2B7. We also confirmed the noninhibition of CYP3A4 and P-gp by other synthetic food dyes. Part of this inhibition depended upon the reaction of (1)O(2) originating on xanthene dyes by light irradiation, because inhibition was prevented by (1)O(2) quenchers. We studied the influence of superoxide dismutase and catalase on this inhibition by dyes and we found prevention of inhibition by superoxide dismutase but not catalase. This result suggests that superoxide anions, originating on dyes by light irradiation, must attack drug-metabolizing enzymes. It is possible that red cosmetics containing phloxine, erythrosine, or rose bengal react with proteins on skin under lighting and may lead to rough skin.
Assuntos
Inibidores das Enzimas do Citocromo P-450 , Inibidores Enzimáticos/toxicidade , Corantes de Alimentos/toxicidade , Glucuronosiltransferase/antagonistas & inibidores , Xantenos/toxicidade , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Corante Amaranto/toxicidade , Hidrocarboneto de Aril Hidroxilases/antagonistas & inibidores , Compostos Azo/toxicidade , Benzenossulfonatos/toxicidade , Transporte Biológico/efeitos dos fármacos , Catalase/farmacologia , Citocromo P-450 CYP2A6 , Citocromo P-450 CYP3A , Inibidores do Citocromo P-450 CYP3A , Eritrosina/toxicidade , Fluoresceínas/toxicidade , Humanos , Índigo Carmim/toxicidade , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Naftalenossulfonatos , Rodaminas/toxicidade , Rosa Bengala/toxicidade , Superóxido Dismutase/farmacologia , Tartrazina/toxicidadeRESUMO
The toxicity of different substances was studied on the protozoan Tetrahymena pyriformis, using as an endpoint the DNA content of the macronucleus. Substances from various chemical classes were administered to the Tetrahymena cultures and then the DNA content of the protozoan macronuclei was measured by means of Image Analysis System. The increase in the DNA content of the nuclei is indicative of the stimulation of the mitotic process. Since mitogenic stimuli can substantially alter susceptibility to chemical carcinogenesis, the results of such experiments, which are cheap and easy to run, may contribute to the investigation of the toxic action of several substances on cellular level.