Ameliorative effects of thymoquinone on the caspase 3, kidney function and oxidative stress tartrazine-induced nephrotoxicity.

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.

Ginkgo biloba extract protects against tartrazine-induced testicular toxicity in rats: involvement of antioxidant, anti-inflammatory, and anti-apoptotic mechanisms.

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.

The protective effect of aqueous extract of Stevia rebaudiana against tartrazine toxicity in male Wistar rat.

Tartrazine is a yellow colouring agent that is commonly used in foods; however, high dosages of Tartrazine affect fertility and create oxidative stress by generating free radicals. A plant species known as Stevia rebaudiana has natural antioxidants that show promise for protecting testicular tissue. Consequently, this study was intended to examine the ameliorative effect of the aqueous extract of S. rebaudiana (Stevia) on the fertility of male Wistar rats induced by the daily oral intake of Tartrazine. Utilizing gas chromatography-mass spectrometry, phytochemical identification was accomplished for Stevia extract. Study groups were separated into several groups: the first group (the control) got distilled water for up to 56 days; the Stevia group (1000 mg/kg), the Tartrazine group (300 mg/kg) and the Stevia and Tartrazine group (the group was given Tartrazine after 1 h of Stevia extract intake). Also, the oxidative damage in testicular tissues was assessed by measuring the levels of malondialdehyde (MDA) and antioxidants (catalase [CAT], superoxide dismutase [SOD] and glutathione reductase [GSH]). Further, histological alterations were examined. In addition, cyclic AMP-responsive element modulator (Crem) gene expression levels and their relative proteins were measured in the testicular tissues using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assays, respectively. Sperm analysis and testosterone concentration were also performed. SPSS version 25 was used for the analysis of results while (p < .05) was regarded as significant. Compared with the control group, the results demonstrated that Tartrazine caused a significant reduction (p < .05) in the testosterone hormone level (0.70 ± 0.21) and the Crem protein quantity (1.21 ± 0.23) in the treated Tartrazine group. Also, it had a significant decrease (p < .05) in sperm motility, viability, count and antioxidant levels. Moreover, there was a significant increase (p < .05) in sperm abnormalities, MDA level (7.40 ± 1.10), kidney and liver function parameters, and DNA degradation in the treated Tartrazine group compared with the control group. On the contrary, the Stevia extract intake enhanced the testosterone (2.50 ± 0.60), antioxidants and Crem protein levels (2.33 ± 0.10) with an improvement in sperm quality in the Stevia and Tartrazine-treated group compared with the Tartrazine group. Stevia also caused a significant decrease (p < .05) in the MDA level (3.20 ± 0.20), and sperm abnormalities with an enhancement of the liver and kidney function parameters in the Stevia and Tartrazine-treated group compared to the Tartrazine group. Stevia administration has a protective effect on the testicular tissues and sperm quality against toxicity induced by Tartrazine exposure, so it will be a good antioxidant drug to be administered daily before daily administration of Tartrazine.

Preparation, analysis and toxicity characterisation of the redox metabolites of the azo food dye tartrazine.

Tartrazine (E102, FD&C Yellow 5) is a vibrant yellow azo dye added to many processed foods. The safety of this ubiquitous chemical has not been fully elucidated, and it has been linked to allergic reactions and ADHD in some individuals. In our study, bacterial species isolated from human stool decolourised tartrazine and, upon exposure to air, a purple compound formed. Tartrazine is known to undergo reduction in the gut to sulfanilic acid and 4-amino-3-carboxy-5-hydroxy-1-(4-sulfophenyl)pyrazole (SCAP). These metabolites and their derivatives are relevant to the toxicology of tartrazine. The toxicity of sulfanilic acid has been studied before, but the oxidative instability of SCAP has previously prevented full characterisation. We have verified the chemical identity of SCAP and confirmed that the purple-coloured oxidation derivative is 4-(3-carboxy-5-hydroxy-1-(4-sulfophenyl)-1H-pyrazol-4-yl)imino-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (purpurazoic acid, PPA), as proposed by Westöö in 1965. A yellow derivative of SCAP is proposed to be the hydrolysed oxidation product, 4,5-dioxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid. SCAP and PPA are moderately toxic to human cells (IC50 89 and 78 µM against HEK-293, respectively), but had no apparent effect on Escherichia coli and Bacillus subtilis bacteria. These results prompt further analyses of the toxicology of tartrazine and its derivatives.

Azo dyes in the food industry: Features, classification, toxicity, alternatives, and regulation.

Azo dyes, including Tartrazine, Sunset Yellow, and Carmoisine, are added to foods to provide color, but they have no value with regard to nutrition, food preservation, or health benefits. Because of their availability, affordability, stability, and low cost, and because they provide intense coloration to the product without contributing unwanted flavors, the food industry often prefers to use synthetic azo dyes rather than natural colorants. Food dyes have been tested by regulatory agencies responsible for guaranteeing consumer safety. Nevertheless, the safety of these colorants remains controversial; they have been associated with adverse effects, particularly due to the reduction and cleavage of the azo bond. Here, we review the features, classification, regulation, toxicity, and alternatives to the use of azo dyes in food.

Analysis of Melatonin-Modulating Effects Against Tartrazine-Induced Neurotoxicity in Male Rats: Biochemical, Pathological and Immunohistochemical Markers.

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.

Cytotoxic and mutagenic effects of the food additive tartrazine on eukaryotic cells.

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.

Riboflavin attenuates tartrazine toxicity in the cerebellar cortex of adult albino rat.

Tartrazine is a synthetic yellowish dye considered one of the most common food colorants. Extensive usage of tartrazine in humans led to harmful health impacts. To investigate the impact of tartrazine administration on the cerebellum and to assess the potential role of riboflavin co-administration in the adult male albino rat. Four groups of adult albino rats were included in this study. Group I was supplied with distilled water. Group II was supplied tartrazine orally at a dose of 7.5 mg/kg BW dissolved in distilled water. Group III was supplied with tartrazine at the same previously mentioned dose and riboflavin orally at a dose of 25 mg/kg BW dissolved in distilled water. Group IV was supplied with riboflavin at the same previously mentioned dose. The study was conducted for 30 days then rats were sacrificed, weighted and the cerebella extracted and handled for light, ultrastructural and immunohistochemical evaluation. It was found with tartrazine treatment focal areas of Purkinje cell loss leaving empty spaces, a broad spread of neuronal affection to the degree of the disappearance of some of the granular cells, reduced the thickness of the molecular and granular layers, and strong positive GFAP immunoreactions. With riboflavin coadministration restored continuous Purkinje layer with normal appeared Purkinje cells, but some cells were still shrunken and vacuolated as well as the molecular and granular cell layers appeared normal. Tartrazine had deleterious effects on the cerebellar cytoarchitecture, and riboflavin co-administration alleviated these neurotoxic effects.

Effects of Tartrazine on Some Sexual Maturation Parameters in Immature Female Wistar Rats.

Over the past century, the average age for onset of puberty has declined. Several additives present in our food are thought to contribute significantly to this early puberty which is recognized to also affect people's health in later life. On this basis, the impact of 40-days unique oral administration of the food dye tartrazine (7.5, 27, and 47 mg/kg BW doses) was evaluated on some sexual maturation parameters on immature female Wistar rats. Vaginal opening was evaluated during the treatment period. At the end of the treatments, animals were sacrificed (estrus phase) and the relative weight of reproductive organs, pituitary gonadotrophin and sexual steroids level, cholesterol level in ovaries and folliculogenesis were evaluated. Compared to the control group, animals receiving tartrazine (47 mg/kg BW) showed significantly high percentage of early vaginal opening from day 45 of age, and an increase in the number of totals, primaries, secondaries, and antral follicles; a significant increase in serum estrogen, LH and in uterine epithelial thickness. Our findings suggest that tartrazine considerably disturbs the normal courses of puberty. These results could validate at least in part the global observations on increasingly precocious puberty in girls feeding increasingly with industrially processed foods.

Impacts of an azo food dye tartrazine uptake on intestinal barrier, oxidative stress, inflammatory response and intestinal microbiome in crucian carp (Carassius auratus).

Food dyes, or color additives, are often added into foods, cosmetics and beverages during processing to improve the sensory attributes of the final products. However, the toxicity of tartrazine (TZ), one of the most common azo-dyes, is still unclear, and needs to be ascertained by further study. Hence, in the present study, we aimed to evaluate the effects of TZ consumption on health by using a teleost, crucian carp (Carassius auratus) as the experimental fish. TZ consumption (1.4, 5.5 and 10 mg/kg bwt/day) could cause severe histopathological and cellular alterations in intestine and liver. The height of intestinal villus, thickness of intestinal muscle, and microvilli density were also affected. With the increasing of TZ concentrations, the activities of antioxidant enzymes (CAT, SOD and GSH-Px), exhibited a decreasing trend, while the contents of MDA elevated. Upregulations of pro-inflammatory cytokines (il6 and tnfα), anti-inflammatory cytokines (il8, and il10) and other immune related genes (complement component 3 (c3), lysozymes (lyz), ß-defensin 3 (defb3)), were observed after TZ uptake. In addition, TZ consumption also affected the community structure of the microbiota in the intestine of crucian carp. The amount of some probiotic bacteria (Roseomonas, Rhodococcus and Bacillus) and the bacteria (Bacteroides and Clostridium), producing short chain fatty acids, were significantly reduced, and some pathogenetic microorganisms (e.g. Bdellovibrio and Shewanella) were significantly increased after TZ uptake. In summary, the data in the present study indicate that TZ consumption, even at a low concentration, may lead to adverse effects on fish health. Therefore, in aquaculture, it is necessary to be informed about the hazardous effects of TZ, and more attentions should be focused on using natural substitutes.

Latest advances on the nanomaterials-based electrochemical analysis of azo toxic dyes Sunset Yellow and Tartrazine in food samples.

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.

Testing in vitro tools for the prediction of cholestatic liver injury induced by non-pharmaceutical chemicals.

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.

In vitro estrogenic, cytotoxic, and genotoxic profiles of the xenoestrogens 8-prenylnaringenine, genistein and tartrazine.

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.

[Tartrazine induces genotoxicity in lympocytes of BALB/c Mus musculus]. / La tartrazina induce genotoxicidad en linfocitos de Mus musculus BALB/c.

OBJECTIVES.: To determine the genotoxic effect of tartrazine on peripheral blood lymphocytes of BALB/c Mus musculus. MATERIALS AND METHODS.: An experimental study was carried out using five groups, with five mice in each group. Their weight was registered for 17 weeks, and at week 15 they were administered physiological saline solution (negative control), potassium dichromate at 25 mg/kg body weight (bw) (positive control) and tartrazine at doses of 0.75 mg/kg bw, 7.5 mg/kg bw and 75 mg/kg bw, for seven days, with the exception of the positive control which was a single dose. Then, every 24 hours, a peripheral blood sample was obtained from the tail, which was then smeared, dried and stained. Subsequently, 1000 lymphocytes were counted for each sample from each mouse, for all treatment groups. RESULTS.: The three tartrazine treatments did not cause significant differences in the weight of mice at week 15, but did produce significant differences in the frequency of micronucleated lymphocytes, with the 75 mg/kg bw tartrazine treatment having the greatest genotoxic effect, inducing an average of 1.63 ± 0.08 micronucleated lymphocytes, compared to the positive control which obtained an average of 1.42 ± 0.08 micronucleated lymphocytes. CONCLUSIONS.: Tartrazine produced a genotoxic effect, increasing the number of micronucleated lymphocytes, at doses of 0.75; 7.5 and 75 mg/kg bw and did not affect body weight during seven days of administration to BALB/c M. musculus.

OBJETIVOS.: Determinar el efecto genotóxico de la tartrazina en linfocitos de sangre periférica de Mus musculus BALB/c. MATERIALES Y MÉTODOS.: Se realizó un estudio experimental, a través de cinco grupos, con cinco ratones en cada uno. Se les registró el peso durante 17 semanas y, en la semana 15 se les administró suero fisiológico (control negativo), dicromato de potasio 25 mg/kg de peso corporal (pc) (control positivo) y tartrazina a dosis de 0,75 mg/kg pc, 7,5 mg/kg pc y 75 mg/kg pc, durante siete días, a excepción del control positivo que fue en dosis única. Luego, cada 24 h se obtuvo una muestra de sangre periférica de la cola y se realizó el frotis, secado y coloración. Posteriormente, se realizó el conteo de 1000 linfocitos por muestra de cada ratón, en todos los tratamientos. RESULTADOS.: Los tres tratamientos con tartrazina no causaron diferencias significativas en el peso de ratones a la semana 15, pero sí produjeron diferencias significativas en la frecuencia de linfocitos micronucleados, siendo el tratamiento con tartrazina de 75 mg/kg pc el de mayor efecto genotóxico, induciendo un promedio de 1,63 ± 0,08 linfocitos micronucleados, comparado con el control positivo que generó un promedio de 1,42 ± 0,08 linfocitos micronucleados. CONCLUSIONES.: La tartrazina produjo un efecto genotóxico, incrementando el número de linfocitos micronucleados, a dosis de 0,75; 7,5 y 75 mg/kg pc y no afecta el peso corporal durante siete días de administración en M. musculus BALB/c.

Combine colorants of tartrazine and erythrosine induce kidney injury: involvement of TNF-α gene, caspase-9 and KIM-1 gene expression and kidney functions indices.

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.

Regulatory Role of Nano-Curcumin against Tartrazine-Induced Oxidative Stress, Apoptosis-Related Genes Expression, and Genotoxicity in Rats.

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.

Effects of Tartrazine on Neural Tube Development in the Early Stage of Chicken Embryos.

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.

Honey attenuates the toxic effects of the low dose of tartrazine in male rats.

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.

High-Dose Aspirin Reverses Tartrazine-Induced Cell Growth Dysregulation Independent of p53 Signaling and Antioxidant Mechanisms in Rat Brain.

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.

Influence of the long-term exposure to tartrazine and chlorophyll on the fibrogenic signalling pathway in liver and kidney of rats: the expression patterns of collagen 1-α, TGFß-1, fibronectin, and caspase-3 genes.

Colouring agents are highly present in diverse products in the human environment. We aimed to elucidate the fibrogenic cascade triggered by the food dyes tartrazine and chlorophyll. Rats were orally given distilled water, tenfold of the acceptable daily intake of tartrazine, or chlorophyll for 90 consecutive days. Tartrazine-treated rats displayed a significant rise (p < 0.05) in the mRNA levels and immunohistochemical localization of the renal and hepatic fibrotic markers collagen 1-α, TGFß-1, and fibronectin and the apoptotic marker caspase-3. Moreover, a significant increment (p < 0.05) in the levels of AST, ALP, creatinine, and urea was evident in both experimental groups but more significant differences were noticed in the tartrazine group. Furthermore, we found a marked increment in the MDA level and significant declines (p < 0.05) in the levels of the SOD, CAT, and GSH enzymes in the kidney and liver from tartrazine-treated rats. The histological investigation reinforced the aforementioned data, revealing hepatocytes with fibrous connective tissue proliferation, apoptotic hepatocytes and periportal fibrosis with tubular necrosis, and shrunken glomeruli and interstitial fibrous tissue proliferation. We concluded that, even at the exposure to high concentrations for long durations, chlorophyll exhibited a lower propensity to induce fibrosis, apoptosis, and histopathological perturbations than tartrazine.