臺灣博碩士論文加值系統

檸檬黃 (Tartrazine, TTZ) 是一種單偶氮吡唑啉酮化合物，為世界上廣泛使用的人工合成著色劑之一，並在各國間合法使用於食品中，然而仍有對人體健康安全之疑慮，故本研究探討檸檬黃對小鼠神經母瘤細胞 (Mouse neuroblastoma cell, N2a cell) 之毒性作用及凋亡相關特徵。採用 N2a 細胞作為細胞模式，探討檸檬黃對其造成之細胞毒性及各項生物活性指標之變化。首先，檸檬黃以連續稀釋濃度暴露於 N2a 細胞 24 小時後，以細胞存活率試驗測定其半最大抑制濃度 (Half maximal inhibitory concentration, IC50) 為 6.334 mM，以此結果設計後續實驗之檸檬黃濃度為分別為 4、5、6 及 7 mM。檸檬黃暴露時間為 24 小時，細胞存活率之結果顯示所有實驗組濃度與控制組相比，皆顯著降低，證實其具有細胞毒性；細胞型態變化之觀測結果顯示檸檬黃會導致 N2a 細胞型態萎縮並產生凋亡特徵；生物活性指標如乳酸去氫酶 (Lactate dehydrogenase, LDH) 釋放量的增加及肌酸肌酶 (Creatine kinase, CK) 活性的上升顯示檸檬黃誘導細胞損傷及代謝指標異常。後續則探討檸檬黃作用於 N2a 細胞之細胞凋亡相關特徵表現。將檸檬黃暴露於細胞 24 小時，細胞之氧化還原指標如活性氧物質 (Reactive oxygen species, ROS) 的增加及總抗氧化能力 (Total antioxidant capacity, TAC) 的下降顯示檸檬黃破壞細胞氧化還原系統之平衡；粒腺體損傷指標如粒腺體膜電位 (Mitochondrial membrane potential, MMP) 的下降及腺苷三磷酸酶 (Adenosine triphosphatase, ATPase) 的活性下降顯示細胞之粒腺體功能遭受破壞；細胞凋亡特定蛋白 Caspase 3/7 的活性增加顯示細胞凋亡啟動因子被活化，進而執行細胞凋亡機制。綜合上述結果，檸檬黃能造成 N2a 細胞之毒性作用及細胞體萎縮變形，降低生物活性指標，破壞生物體氧化還原之平衡，造成粒腺體損傷，最終活化凋亡蛋白啟動細胞凋亡。

Tartrazine (TTZ) is a monoazo pyrazolone compound of artificial pigment, which has been used in every country in the world. However, there are still some issues about human health and safty. Cytotoxity and apoptosis features induced by tartrazine in N2a cell was explored in this study. N2a cell was used as a model to explore cytotoxicity and the changes of various biological activity indicators caused by tartrazine. First, tartrazine was exposed to N2a cell at a serial dilution concentration for 24 hours, and then its half maximal inhibitory concentration (IC50) was 6.334 mM as determined by cell viability test. Based on this result, the tartrazine concentration in the subsequent experiments was designed to be 4, 5, 6 and 7 mM. The exposure time of tartrazine was 24 hours. The results of cell viability test showed that all treatment groups were significantly lower than the control group, confirming that tartrazine was cytotoxic. The changes of cellular morphology showed that tartrazine caused N2a cell atrophy and apoptosis features. The changes of biological activity indicators such as increasing release of lactate dehydrogenase (LDH) and activity of creatine kinase (CK) indicated that tartrazine induced cell damage and abnormal metabolic indicators. Then, tartrazine was exposed to N2a cell for 24 hours. The changes of the redox indicators such as increasing reactive oxygen species (ROS) and decreasing total antioxidant capacity (TAC) showed that tartrazine broke the balance of redox system in N2a cell. The changes of the mitochondrial damage indicators such as decreasing mitochondrial membrane potential (MMP) and activity of adenosine triphosphatase (ATPase) indicated that the function of the mitochondria of the cell was damaged. The increasing activity of the apoptosis-specific protein caspase 3/7 showed that the apoptosis initiation factor was activated, which in turn performed the apoptosis mechanism. Based on the above results, tartrazine can cause the cytotoxic effect and atrophy of N2a cells, reduce the biological activity indicators, break the redox balance of the organism, damage the function of the mitochondria, and activate the apoptosis protein to initiate apoptosis.

摘要 I
Abstract II
壹、文獻整理 1
一、檸檬黃 (Tartrazine, TTZ) 之簡介 2
(一) 著色劑之簡介 2
(二) 歷史 2
(三) 化學結構 2
(四) 物化特性 3
(五) 製取 3
(六) 安全性 3
(七) 食用危害性及毒理性 4
(八) 毒性作用機制 4
二、檸檬黃之檢測方法 5
(一) 簡介 5
(二) 檢測儀器 5
三、細胞死亡途徑 7
(一) 細胞壞死 7
(二) 細胞凋亡 8
(三) 流式細胞儀 10
貳、研究內容 11
第一章、探討檸檬黃造成小鼠神經母瘤細胞之毒性作用及生物活性指標 12
一、前言 12
二、材料與方法 13
三、結果 18
四、討論 20
五、圖表 23
第二章、探討檸檬黃誘導小鼠神經母瘤細胞之細胞凋亡相關特徵 32
一、前言 32
二、材料與方法 33
三、結果 37
四、討論 39
五、圖表 43
參、總結論 52
肆、參考文獻 53
伍、附錄 64
謝辭 70

行政院衛生福利部食品藥物管理署，2020。食品添加物使用範圍及限量暨規格標準。台北，台灣。
吳尚宜，2017。基隆產珊瑚菟葵種屬的基因鑑定及其毒素對細胞毒性之探討。國立臺灣海洋大學食品科學系碩士學位論文。基隆，台灣。
邱家蓁，2016。探討牛磺酸與維生素 C 作為肺癌細胞株暴露 Benzo [α] Pyrene (BaP) 之預防效果。國立臺灣海洋大學食品科學系碩士學位論文。基隆，台灣。
黃育琳，2019。以小鼠神經 N2a 細胞模式探討視黃醇之細胞毒性。國立臺灣海洋大學食品科學系碩士學位論文。基隆，台灣。
葉子寧，2018。基隆產珊瑚菟葵 Palythoa tuberculosa 之季節毒性分析及菟葵毒萃取液之細胞毒性探討。國立臺灣海洋大學食品科學系碩士學位論文。基隆，台灣。
裴軼勁、黃梅、郭林明、吳小蘭、劉俊康，2009。ATP 酶在細菌潛生體相關的IBS大鼠模型腸黏膜中的變化。世界華人消化雜誌 17(8): 817-820。重慶，中國。
賴昱維，2018。高效液相層析搭配二極體陣列檢測器與四極軸軌道捕捉式質譜儀多重分析魚乾、魚卵及蝦米中 23 種人工合成著色劑。國立臺灣海洋大學食品科學系碩士學位論文。基隆，台灣。
Abdel-Aziz, H. M., Alazouny, Z. M., Abdelfadee, K. F. and Abohashem, A. A. 2019. Effect of tartrazine on thyroid gland of male rat and ameliorating role of curcumin (histological and immunohistochemical study). Journal of Biochemistry and Cell Biology 2(111): 2.
Abd-Elhakim, Y. M., Moustafa, G. G., Hashem, M. M., Ali, H. A., Abo-EL-Sooud, K. and El-Metwally, A. E. 2019. 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, TGFβ-1, fibronectin, and caspase-3 genes. Environmental Science and Pollution Research 26(12): 12368-12378.
Al-Degs, YS. 2009. Determination of three dyes in commercial soft drinks using HLA/GO and liquid chromatography. Food Chemistry 117: 485-490.
Amin, F. A. S. M. 2018. Pathophysiological effects of azorubine on female reproductive organs and hormones in Sprague Dawley® rat. International Journal of Medical Research and Health Sciences 7(6): 57-62.
Amado, L. L., Garcia, M. L., Ramos, P. B., Freitas, R. F., Zafalon, B., Ferreira, J. R., Yunes, J. S. and Monserrat, J. M. 2009. A method to measure total antioxidant capacity against peroxyl radicals in aquatic organisms: Application to evaluate microcystins toxicity. Science of the Total Environment 407: 2115-2123.
Ameur, F. Z., Mehedi, N., Kheroua, O., Saïdi, D., Salido, G. M. and Gonzalez, A. 2018. Sulfanilic acid increases intracellular free-calcium concentration, induces reactive oxygen species production and impairs trypsin secretion in pancreatic AR42J cells. Food and Chemical Toxicology 120: 71-80.
Amin, K. A., Hameid II, H. A. and Elsttar, A. A. 2010. Effect of food azo dyes tartrazine and carmoisine on biochemical parameters related to renal, hepatic function and oxidative stress biomarkers in young male rats. Food and Chemical Toxicology 48(10): 2994-2999.
Ashida, H., Hashimoto, T., Tsuji, S., Kanazawa, K. and Danno, G. I. 2000. Synergistic effects of food colors on the toxicity of 3-amino-1, 4-dimethyl-5H-pyrido [4, 3-b] indole (Trp-P-1) inprimary cultured rat hepatocytes. Journal of Nutritional Science and Vitaminology 46: 130-136.
Axon, A., May, F. E., Gaughan, L. E., Williams, F. M., Blain, P. G. and Wright, M. C. 2012. Tartrazine and sunset yellow are xenoestrogens in a new screening assay to identify modulators of human oestrogen receptor transcriptional activity. Toxicology 298: 40-51.
Bárány, M. 1967. ATPase activity of myosin correlated with speed of muscle shortening. The Journal of General Physiology 50(6): 197-218.
Bastaki, M., Farrell, T., Bhusari, S., Pant, K. and Kulkarni, R. 2017. Lack of genotoxicity in vivo for food color additive Allura Red AC. Food and Chemical Toxicology 105: 308-314.
Bezerra, M. S., Malaquias, G. S., Sousa, J. M. C. and Peron, A. P. 2016. Cytotoxic and genotoxic potential of powdered juices. Food Science and Technology (Campinas) 36: 49-55.
Bhatia, M. S. 2000. Allergy to tartrazine in psychotropic drugs. The Journal of Clinical Psychiatry 61: 473-476.
Boussada, M., Lamine, J. A., Bini, I., Abidi, N., Lasrem, M., El-Fazaa, S. and El-Golli, N. 2017. Assessment of a sub-chronic consumption of tartrazine (E102) on sperm and oxidative stress features in Wistar rat. International Food Research Journal 24(4): 1473-1481.
Brentnall, M., Rodriguez-Menocal, L., De Guevara, R. L., Cepero, E. and Boise, L. H. 2013. Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis. BMC Cell Biology 14: 1-9.
Burlingham, B. T. and Widlanski, T. S. 2003. An intuitive look at the relationship of Ki and IC50: a more general use for the Dixon plot. Journal of Chemical Education 80: 214-218.
Caldas, L. Q., Morais, L., Piumbini, R., Pascoto, C. and Lobo, W. 2008. A double-blind, randomized and crossed over controlled study of the immunereactivity of atopic patients challenged with the yellow colorant tartrazine. Toxicology Letters 180: S208-S209.
Chan, F. K. M., Moriwaki, K. and De Rosa, M. J. 2013. Detection of necrosis by release of lactate dehydrogenase activity. In: Immune Homeostasis (eds. by Snow, A. L. and Lenardo, M. J.) pp. 65-70. Humana Press. Totowa, N. J., U. S. A.
Chen, L. B. 1988. Mitochondrial membrane potential in living cells. Annual Review of Cell Biology 4: 155-181.
Chung, K. T. and Cerniglia, C. E. 1992. Mutagenicity of azo dyes: structure-activity relationships. Mutation Research 277(3): 201-220.
Chung, K. T., Fulk, G. E. and Egan, M. 1978. Reduction of azo dyes by intestinal anaerobes. Applied and Environmental Microbiology 35: 558-562.
Christofferson, D. E. and Yuan, J. 2010. Necroptosis as an alternative form of programmed cell death. Current Opinion in Cell Biology 22: 263-268.
Czabotar, P. E., Lessene, G., Strasser, A. and Adams, J. M. 2014. Control of apoptosis by the BCL-2 protein family: Implications for physiology and therapy. Nature Reviews Molecular Cell Biology 15: 49-63.
de Boer, L. 2013. Biotechnological production of colorants. Biotechnology of Food and Feed Additives: 51-189.
Demirkol, O., Adams, C. and Ercal, N. 2004. Biologically important thiols in various vegetables and fruits. Journal of Agricultural and Food Chemistry 52(26): 8151-8154.
Demirkol, O., Zhang, X. and Ercal, N. 2012. Oxidative effects of Tartrazine (CAS No. 1934-21-0) and New Coccin (CAS No. 2611-82-7) azo dyes on CHO cells. Journal für Verbraucherschutz und Lebensmittelsicherheit 7: 229-236.
Devasagayam, T. P. A., Tilak, J. C., Boloor, K. K., Sane, K. S., Ghaskadbi, S. S. and Lele, R. D. 2004. Free radicals and antioxidants in human health: Current status and future prospects. Journal of Association of Physicians of India 52(794804): 4.
Dhandayuthapani, S., Marimuthu, P., Hörmann, V., Kumi-Diaka, J. and Rathinavelu, A. 2013. Induction of apoptosis in HeLa cells via caspase activation by resveratrol and genistein. Journal of Medicinal Food 16(2): 139-146.
Downham, A. and Collins, P. 2000. Colouring our foods in the last and next millennium. International Journal of Food Science and Technology 35: 5-22.
El-Borm, H. T., Badawy, G. M., El-Nabi, S. H. El-Sherif, W. A. and Atallah, M. N. 2019. Efficacy of curcumin on sunset yellow and tartrazine induced hepatotoxicity and nephrotoxicity in the chick embryo Gallus domesticus. European Journal of Pharmaceutical and Medical Research 6(11): 48-64.
El-Desoky, G. E., Abdel-Ghaffar, A., Al-Othman, Z. A., Habila, M. A., Al-Sheikh, Y. A., Ghneim, H. K., Giesy, J. P. and Aboul-Soud, M. A. M. 2017. Curcumin protects against tartrazine-mediated oxidative stress and hepatotoxicity in male rats. European Review for Medical and Pharmacological Sciences 21(3): 635-645.
Elhkim, M. O., Héraud, F., Bemrah, N., Gauchard, F., Lorino, T., Lambré, C., Frémy, J. M. and Poul, J. M. 2007. New considerations regarding the risk assessment on tartrazine an update toxicological assessment, intolerance reactions and maximum theoretical daily intake in France. Regulatory Toxicology and Pharmacology 47: 308-316.
Elmore, S. 2007. Apoptosis: A review of programmed cell death. Toxicologic Pathology 35: 495-516.
Esterbauer, H. 1996. Estimation of peroxidative damage. A critical review. Pathologie-Biologie 44(1): 25-28.
Fadok, V. A., Voelker, D. R., Campbell, P. A., Cohen, J. J., Bratton, D. L. and Henson, P. M. 1992. Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. The Journal of Immunology 148: 2207-2216.
Floriano, J. M., Rosa, E. D., do Amaral, Q. D. F., Zuravski, L., Chaves, P. E. E., Machado, M. M. and de Oliveira, L. F. S. 2018. Is tartrazine really safe? In silico and ex vivo toxicological studies in human leukocytes: A question of dose. Toxicology Research 7(6): 1128-1134.
Frances, D. E. A., Ingaramo, P. I., Ronco, M. T. and Carnovale, C. E. 2013. Diabetes, an inflammatory process: oxidative stress and TNF-alpha involved in hepatic complication. Journal of Biomedical Science and Engineering 6: 645-653.
Gardner, A. M., Xu, F. H., Fady, C., Jacoby, F. J., Duffey, D. C., Tu, Y. and Lichtenstein, A. 1997. Apoptotic vs. nonapoptotic cytotoxicity induced by hydrogen peroxide. Free Radical Biology and Medicine 22: 73-83.
Gelain, D. P. and Moreira, J. C. F. 2007. Evidence of increased reactive speciesformation by retinol, but not retinoic acid, in PC12 cells. Toxicology in Vitro 22: 553-558.
Giri, A. K., Das, S. K., Talukder, G. and Sharma, A., 1990. Sister chromatid exchange and chromosome aberrations induced by curcumin and tartrazine on mammalian cells in vivo. Cytobios 62: 111-117.
Gomes, K. M. S., de Oliveira, M. V. G. A., Carvalho, F. R. D., Menezes, C. C. and Peron, A. P. 2013. Citotoxicity of food dyes sunset yellow (E-110), bordeaux red (E-123), and tatrazine yellow (E-102) on Allium cepa L. root meristematic cells. Journal of Food Science and Technology (Campinas) 33: 218-223.
Groner, J. A., Huang, H., Eastman, N., Lewis, L., Joshi, M. S., Schanbacher, B. L., Nicholson, L. and Bauer, J. A. 2016. Oxidative stress in youth and adolescents with elevated body mass index exposed to secondhand smoke. Nicotine and Tobacco Research 18(7): 1622-1627.
Halliwell, B. 1987. Oxidants and human disease: some new concepts. The Federation of American Societies for Experimental Biology Journal 1(5): 358-364.
Hamasaki, K., Kogure, K. and Ohwada, K. 1996. A biological method for the quantitative measurement of tetrodotoxin (TTX): Tissue culture bioassay in combination with a water-soluble tetrazolium salt. Toxicon 34(4): 490-495.
Hargreaves, A. J., Sachana, M. and Flaskos, J. 2014. Cytoskeletal disruption as a biomarker of developmental neurotoxicity. In: Biomarkers in Toxicology (eds. by Gupta, R.). Elsevier Press. California. U.S.A. pp. 833-845.
Helal, E. G., Zaahkouk, S. A. and Mekkawy, H. A. 2000. Effect of Some Food Colorants (Synthetic andNatural products) of Young Albino Rats. The Egyptian Journal of Hospital Medicine 1(1): 103-113.
Henson, P. M. 2003. The final step in programmed cell death: phagocytes carry apoptotic cells to the grave. Essays in Biochemistry 39: 105-117.
Hildenbrand, S., Schmahl, F. W., Wodarz, R., Kimmel, R. and Dartsch, P. C. 1999. Azo dyes and carcinogenic aromatic amines in cell cultures. International Archives of Occupational and Environmental Health 72: M052-M056.
Himri, I., Bellahcen, S., Souna, F., Belmekki, F., Aziz, M., Bnouham, M., Zoheir, J., Berkia, Z., Mekhfi, H. and Saalaoui, E. 2011. A 90-day oral toxicity study of tartrazine, a synthetic food dye, in wistar rats. International Journal of Pharmacy and Pharmaceutical Sciences 3(3): 159-169.
Himri, I., Souna, F., Aziz, M., Hakkou, A. and Saalaoui, E. 2012. DNA Damage induced by tartrazine in rat whole blood using comet assay (single cell gel electrophoresis). Advances in Environmental Biology 6: 2875-2881.
Holler, N., Zaru, R., Micheau, O., Thome, M., Attinger, A., Valitutti, S. and Tschopp, J. 2000. Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nature Immunology 1: 489.
Hoodless, R. A., Thomson, J. and Arnold, J. E. 1971. Separation and identification of food colours: Part II. Identification of synthetic oil-soluble food colours using thin-layer chromatography. Journal of Chromatography A56: 332-337.
Ishidate, M Jr., Sofuni, T. and Yoshikawa, K. 1981. Chromosomal aberration tests in vitro as a primary screening tool for environmental mutagens and/or carcinogens. Gann Monograph on Cancer Research 27: 95-108.
Ishidate, M. Jr., Sofuni, T., Yoshikawa, K., Hayashi, M., Nohmi, T., Sawada, M. and Matsuoka, A. 1984. Primary mutagenicity screening of food additives currently used in Japan. Food and Chemical Toxicology 22: 623-636.
Jain, R., Bhargava, M. and Sharma, N. 2003. Electrochemical studies on a pharmaceutical azo dye: Tartrazine. Industrial and Engineering Chemistry Research 42(2): 243-247.
Kaplan, J. H. 2002. Biochemistry of na, K-ATPase. Annual Review of Biochemistry 71(1): 511-535.
Kashanian, S. and Zeidali, SH. 2011. DNA Binding studies of tartrazine food additive. DNA and Cell Biology 30: 499-505.
Khayyat, L., Essawy, A., Sorour, J. and Soffar, A. 2017. Tartrazine induces structural and functional aberrations and genotoxic effects in vivo. Peerj 5: 1-14.
Klamt, F., De Oliveira, M. R. and Moreira, J. C. F. 2005. Retinol induces permeability transition and cytochrome c release from rat liver mitochondria. Biochimica et Biophysica Acta (BBA)-General Subjects 1726: 14-20.
Krammer, P. H. 2000. CD95's deadly mission in the immune system. Nature 407: 789-795.
Koh, J. Y. and Choi, D. W. 1987. Quantitative determination of glutamate mediated cortical neuronal injury in cell culture by lactate dehydrogenase efflux assay. Journal of Neuroscience Methods 20: 83-90.
Koutsogeorgopoulou, L., Maravelias, C., Methenitou, G. and Koutselinis, A. 1998. Immunological aspects of the common food colorants, amaranth and tartrazine. Veterinary and Human Toxicology 40(1): 1-4.
Kucharska, M. and Grabka, J. 2010. A review of chromatographic methods for determination of synthetic food dyes. Talanta 80: 1045-1051.
Lavrik, I. N. and Krammer, P. H. 2012. Regulation of CD95/Fas signaling at the DISC. Cell Death and Differentiation 19: 36-41.
Li, H., Xiang, L., Yang, N., Cao, F., Li, C., Chen, P., Ruan, X., Feng, Y., Zhou, N. and Wang, X. 2018. Zhiheshouwu ethanol extract induces intrinsic apoptosis and reduces unsaturated fatty acids via SREBP1 pathway in hepatocellular carcinoma cells. Food and Chemical Toxicology 119: 169-175.
López‐de‐Alba, P. L., López‐Martínez, L. and De‐León‐Rodríguez, L. M. 2002. Simultaneous determination of synthetic dyes tartrazine, allura red and sunset yellow by differential pulse polarography and partial least squares. A multivariate calibration method. Electroanalysis 14: 197-205.
Ly, J. D., Grubb, D. R. and Lawen, A. 2003. The mitochondrial membrane potential (Δψm) in apoptosis: An update. Apoptosis 8: 115-128.
McCann, D., Barrett, A., Cooper, A., Crumpler, D., Dalen, L., Grimshaw, K., Kitchin, E., Lok, K., Porteous, L., Prince, E., Sonuga-Barke, E., Warner, J. O. and Sonuga-Barke, E. 2007. Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: A randomised, double-blinded, placebo-controlled trial. The Lancet 370(9598): 1560-1567.
Mehedi, N., Mokrane, N., Alami, O., Ainad-Tabet, S., Zaoui, C., Kheroua, O. and Saidi, D. 2013. A thirteen week ad libitum administration toxicity study of tartrazine in Swiss mice. African Journal of Biotechnology 12: 4519-4529.
Micheau, O. and Tschopp, J. 2003. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 114: 181-190.
Mosmann, T. 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of Immunological Methods 65: 55-63.
Moutinho, I. L. D., Bertges, L. C., and Assis, R. V. C. 2007. Prolonged use of the food dye tartrazine (FD&C yellow n° 5) and its effects on the gastric mucosa of Wistar rats. Brazilian Journal of Biology 67: 141-145.
Mpountoukas, P., Pantazaki, A., Kostareli, E., Christodoulou, P., Kareli, D., Poliliou, S., Mourelatos, C., Lambropoulou, V. and Lialiaris, T. 2010. Cytogenetic evaluation and DNA interaction studies of the food colorants amaranth, erythrosine and tartrazine. Food and Chemical Toxicology 48: 2934-2944.
Nagaraja, T. N. and Desiraju, T. 1993. Effects of chronic consumption of metanil yellow by developing and adult rats on brain regional levels of noradrenaline, dopamine and serotonin, on acetylcholine esterase activity and on operant conditioning. Food and Chemical Toxicology 31: 41-44.
Nagata, S. 1997. Apoptosis by death factor. Cell 88: 355-365.
Nagata, S. 2018. Apoptosis and clearance of apoptotic cells. Annual Review of Immunology 36: 489-517.
Nettis, E., Colanardi, M. C., Ferrannini, A. and Tursi, A. 2003. Suspected tartrazine‐induced acute urticaria/angioedema is only rarely reproducible by oral rechallenge. Clinical and Experimental Allergy 33: 1725-1729.
Newsome, A. G., Culver, C. A. and Van Breemen, R. B. 2014. Nature’s palette: The search for natural blue colorants. Journal of Agricultural and Food Chemistry 62: 6498-6511.
Nikoletopoulou, V., Markaki, M., Palikaras, K. and Tavernarakis, N. 2013. Crosstalk between apoptosis, necrosis and autophagy. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research 1833: 3448-3459.
Oyewole, O. I. and Oladele, J. O. 2016. Assessment of cardiac and renal functions in Wistar albino rats administered carmoisine and tartrazine. Advances in Biochemical Engineering/Biotechnology 4(3): 21-25.
Pankov, R. and Yamada, K. M. 2002. Fibronectin at a glance. Journal of Cell Science 115(20): 3861-3863.
Patterson, R. M. and Butler, J. S. 1982. Tartrazine induced chromosomal aberrations in mammalian cells. Food and Chemical Toxicology 20(4): 461-465.
Petit, P. X. 1992. Flow cytometric analysis of rhodamine 123 fluorescence during modulation of the membrane potential in plant mitochondria. Plant Physiology 98(1): 279-286.
Pintea, A. M. 2008. Synthetic colorants. Food Colorants: Chemical and Functional Properties 7: 603-615.
Poul, M., Jarry, G., Elhkim, M. O. and Poul, J. M. 2009. Lack of genotoxic effect of food dyes amaranth, sunset yellow and tartrazine and their metabolites in the gut micronucleus assay in mice. Food and Chemical Toxicology 47: 443-448.
Rice-Evans, C. and Burdon, R. 1993. Free radical-lipid interactions and their pathological consequences. Progress in Lipid Research 32(1): 71-110.
Safford, R. J. and Goodwin, B. F. J. 1984. The effect of tartrazine on histamine release from rat peritoneal mast cells. International Journal of Immunopharmacology 6(3): 233-240.
Salama, M. S., Ismail, M. A., Shahin, M. A. and Yassin, H. M. 2016. The use of GST-µ Gene and Isoenzymes as biomarkers to evaluate the mutagenicity and hepatic carcinogenicity in the mouse by carmoisine ‘E122’. Merit Research Journal of Medicine and Medical Sciences (MRJMMS) 4(6): 294-316.
Şekeroğlu, Z. A., Güneş, B., Kontaş Y. S., Şekeroğlu, V. and Aydın, B. 2017. Effects of tartrazine on proliferation and genetic damage in human lymphocytes. Toxicology Mechanisms and Methods 27(5): 370-375.
Shuai, Y., Lou, D., Yin, J., Qian, X., Wang, Y., Hong, X., Xiao, P. and Zhong, W. 2017. Characterization of microcystin-induced dualistic toxic effects on primary rat hepatocytes. Journal of Environmental Pathology, Toxicology and Oncology 36(1): 15-27.
Sies, H., Stahl, W. and Sevanian, A. 2005. Nutritional, dietary and postprandial oxidative stress. The Journal of Nutrition 135(5): 969-972.
Simoni, R. D., Hill, R. L. and Vaughan, M. 2002. The discovery of glutathione by F. Gowland Hopkins and the beginning of biochemistry at Cambridge University. Journal of Biological Chemistry 277(24): 27-28.
Sinha, M., Manna, P. and Sil, P. C. 2008. Arjunolic acid attenuates arsenic-induced nephrotoxicity. Pathophysiology 15: 147-156.
Siraki, A. G., Chan, T. S., Galati, G., Teng, S. and O’Brien, P. J. 2002. N-oxidation of aromatic amines by intracellular oxidases. Drug Metabolism Reviews 34 (3): 549-564.
Smith, A., Parkes, M. A. F., Atkin-Smith, G. K. Tixeira, R. and Poon, I. K. H. 2017. Cell disassembly during apoptosis. Journal of Medicine 4: 8-10.
Soares, B. M., Araujo, T. M., Ramos, J. A., Pinto, L. C., Khayat, B. M., de Oliveira Bahia, M., Montenegro R. C., Burbano, R. M. and Khayat, A. S. 2015. Effects on DNA repair in human lymphocytes exposed to the food dye tartrazine yellow. Anticancer Research 35: 1465-1474.
Strasser, A., Jost, P. J. and Nagata, S. 2009. The many roles of FAS receptor signaling in the immune system. Immunity 30: 180-192.
Surh, C. D. and Sprent, J. 1994. T-cell apoptosis detected in situ during positive and negative selection in the thymus. Nature 372: 100-103.
Suzuki, Y., Ishihara, M., Segami, T. and Ito, M. 1998. Anti-ulcer effects of antioxidants, quercetin, α-tocopherol, nifedipine and tetracycline in rats. The Japanese Journal of Pharmacology 78(4): 435-441.
Talaska, G. and Al-Zoughoo, M. 2003. Aromatic Amines and Biomarkers of Human Exposure. Journal of Environmental Science and Health C 21: 133-164.
Timpl, R., Rohde, H., Robey, P. G., Rennard, S. I., Foidart, J. M. and Martin, G. R. 1979. Laminin--a glycoprotein from basement membranes. Journal of Biological Chemistry 254(19): 9933-9937.
Tolman, K. G., Peterson, P., Gray, P. and Hammar, S. P. 1978. Hepatotoxicity of salicylates in monolayer cell cultures. Gastroenterology 74: 205-208.
Townsend, D. M., Tew, K. D. and Tapiero, H. 2003. The importance of glutathione in human disease. Biomedicine and Pharmacotherapy 57(3-4): 145-155.
Varney, J. L., Fowler, J. W., Gilbert, W. C. and Coon, C. N. 2017. Utilisation of supplemented L-carnitine for fuel efficiency, as an antioxidant, and for muscle recovery in Labrador retrievers. Journal of Nutritional Science 6(8): 1-9.
Walczak, H. 2013. Death receptor-ligand systems in cancer, cell death, and inflammation. Cold Spring Harbor Perspectives in Biology 5: 1-18.
Willy, H. and Hunger K. 2004. Azo pigments. In: Industrial Organic Pigments: Production, Properties, Applications (3rd Ed.) (eds. by Willy, H., Hunger, K., Wilker, G., Ohleir, H. and Winter, R.) Wiley-VCH. WeinHeim, Germany.
Wong, W. W. L. and Puthalakath, H. 2008. Bcl-2 family proteins: The sentinels of the mitochondrial apoptosis pathway. IUBMB Life 60: 390-397.
Yuan, S. and Akey, C. W. 2013. Apoptosome structure, assembly, and procaspase activation. Structure 21: 501-515.
Zamzami, N., Maisse, C., Métivier, D. and Kroemer, G. 2001. Measurement of membrane permeability and permeability transition of mitochondria. Methods in Cell Biology 65: 147-158.
Zhang, H., Sweezey, N. B. and Kaplan, F. 2015. LGL1 modulates proliferation, apoptosis, and migration of human fetal lung fibroblasts. American Journal of Physiology-Lung Cellular and Molecular Physiology 308(4): 391-402.
Zheng, Y., Fu, L., Wang, A. and Cai, W. 2015. Electrochemical detection of quinoline yellow in soft drinks based on layer-by-layer fabricated multi-walled carbon nanotube. International Journal of Electrochemical Science 10: 3530-3538.
Zinser, E., Sperka-Gottlieb, C. D., Fasch, E. V., Kohlwein, S. D., Paltauf, F. R. I. T. Z. and Daum, G. U. N. T. H. E. R. 1991. Phospholipid synthesis and lipid composition of subcellular membranes in the unicellular eukaryote Saccharomyces cerevisiae. Journal of Bacteriology 173(6): 2026-2034.