臺灣博碩士論文加值系統

鯙科魚類 (Muraenidae) 在全世界已有多起因熱帶海魚毒引起的中毒案例，在台灣也曾有食用鯙類後產生頭暈、嘔吐及癱瘓等臨床症狀的病例，其毒素被判斷為有毒渦鞭毛藻所產生的西卡毒素，而發生熱帶性海魚毒之魚類，多數為體型大於 3 kg 之魚體。其次，維生素 A 是人體必需營養素之一，魚肉豐富的維生素A 具有維持視覺健康、免疫系統及抗氧化活性等生理特性，但肝臟為主要累積脂溶性維生素 A 的器官，人類食用魚類肝臟容易發生維生素 A 攝取過量甚至引起中毒的問題。
本研究以基因定序技術，對台灣常見之鯙類進行物種鑑定，使用引子對 Fish F1/Fish R1 和 Fish F2/Fish R2 針對 COXI (cytochrome c oxidase subunit I) 之聚合酶鏈鎖反應，增幅約 707 bp 基因序列，並使用 H15149/Newest-1 和 GYM-Cytb-sen2/GYM-Cytb-ant2 增幅 Cyt b (cytochrome b)片段，序列長度約380 bp，定序後再與資料庫比對以確認物種，分成 12 種鯙類。西卡毒素檢驗以小鼠生物分析法 (mouse bioassay, MBA) 進行，實驗結果顯示，鯙類肌肉組織之毒素皆小於小鼠致死劑量 (< 0.025 MU/g)，但有 28％ 的小鼠在腹腔注射後觀察到腹瀉、呼吸困難或抽搐等症狀，表示鯙類仍有熱帶性海魚毒中毒之風險存在。
維生素 A 以高效液相層析儀 (high performance liquid chromatography, HPLC)，分析鯙類的肌肉及肝臟中維生素 A 含量，實驗結果顯示，肌肉樣品的平均數為 15.79 ± 11.77 IU/g，而肝臟樣品中最高維生素 A 含量為 40,713 IU/g，整個肝臟含量高達 382,701 IU，已超過慢性中毒劑量 100,000 IU，且接近急性中毒劑量500,000 IU。在 50 個樣品中能發現，鯙類體重與肝臟重成正相關，而肝臟重約佔魚體重之 1％，故建議國人避免食用 3 kg 以上大型鯙科魚類，以避免熱帶性海魚毒之中毒，其次可避免攝食太多鯙類肝臟而發生維生素 A 過量中毒之可能性。

There have been multiple cases worldwide of poisoning caused by cigutera fish poisoning in the Muraenidae. In Taiwan, there have also been instances of clinical symptoms such as dizziness, vomiting, and paralysis following the consumption of Muraenidae. The responsible toxin is judged to be ciguatoxin, produced by dinoflagellates. Fish species affected by cigutera fish poisoning are mostly those weighing over 3 kg. Additionally, vitamin A is an essential nutrient for the human body. Fish, rich in vitamin A, possesses physiological properties such as maintaining visual health, bolstering the immune system, and exhibiting antioxidant activity. However, the liver is the main organ for storing fat-soluble vitamin A, making humans susceptible to vitamin A overdose and subsequent poisoning after consuming fish liver.
This study employs gene sequencing technology to identify common Muraenidae species in Taiwan. Primer pairs Fish F1/Fish R1 and Fish F2/Fish R2 were utilized to conduct polymerase chain reaction targeting COXI (cytochrome c oxidase subunit I), resulting in approximately a 707 bp gene sequence. Furthermore, the Cyt b (cytochrome b) fragment was amplified using H15149/Newest-1 and GYM-Cytb-sen2/GYM-Cytb-ant2 primers, with a sequence length of about 380 bp. After sequencing, the data were compared with a database to confirm species identification, revealing 12 Muraenidae species. ciguatoxin testing was conducted via mouse bioassay (MBA). The experimental results indicated that toxin levels in cartilage and muscle tissues were below the lethal dose for mice (< 0.025 MU/g). However, 28% of mice displayed symptoms such as diarrhea, dyspnea, or convulsions after intraperitoneal injection, highlighting the ongoing risk of cigutera fish poisoning from Muraenidae.
High-performance liquid chromatography (HPLC) was utilized to analyze the vitamin A content in Muraenidae muscle and liver tissues. Results showed an average of 15.79 ± 11.77 IU/g in muscle samples. The highest vitamin A content in the liver reached 40,713 IU/g, with a total content of 382,701 IU, surpassing the chronic toxic dose of 100,000 IU and approaching the acute toxic dose of 500,000 IU. In 50 samples, a positive correlation was observed between Muraenidae body weight and liver weight, with the liver weight accounting for about 1% of the fish's body weight. Therefore, it is recommended that individuals avoid consuming large Muraenidae weighing over 3 kg to prevent cigutera fish poisoning and mitigate the risk of vitamin A overdose caused by excessive consumption of fish liver.

摘要 I
Abstract II
目錄 III
壹、文獻整理 1
一、鯙科魚類簡介 2
二、魚種鑑定 6
三、熱帶性海魚毒之西卡毒素 9
四、維生素A 13
貳、研究內容 20
第一章、鯙科魚類之物種鑑定 21
一、前言 21
二、材料與方法 22
三、結果 25
四、討論 27
五、圖表 29
第二章、鯙科魚類之熱帶性海魚毒及維生素 A 含量探討 42
一、前言 42
二、材料與方法43
三、結果 45
四、討論 47
五、圖表 49
參、總結論 61
肆、參考文獻 63
謝辭 76

小枝圭太、何宣慶，2020。台灣南部魚類圖鑑 (第一輯，第二輯)。第二版。國立海洋生物博物館，屏東，台灣。
行政院衛生福利部食品藥物管理署，2010。熱帶性海魚毒 (ciguateric toxin)。台北。
行政院衛生福利部食品藥物管理署，2018。食品中海洋生物讀之檢驗方法-西卡毒素之檢驗。台北。
行政院衛生福利部食品藥物管理署，2024。食品中毒發生與防治年報。台北。
行政院衛生福利部國民健康署，2020。國人膳食營養參考攝取量 (修訂第八版)，台北。
行政院衛生福利部國民健康署，2024。食品成分資料庫(新版)，台北。
林佩宜，2022。臺灣笛鯛科魚類之基因鑑定、西卡毒毒性和維生素 A 含量之探討。國立臺灣海洋大學，基隆市。
陳逸泓，2022。臺灣金梭魚科魚類之物種鑑定、西卡毒性及維生素 A 含量之研究。國立臺灣海洋大學，基隆市。
陳籽伍，2022。台灣常見紅條石斑魚之 PCR-RFLP 鑑定技術、維生素 A 含量及西卡毒毒性之探討。國立臺灣海洋大學，基隆市。
陳鴻鳴，1997。台灣海域鯙科魚類之系統分類研究。國立台灣海洋大學論文。
周先樂，2000。人體生理學初版。藝軒出版社，台北。
徐成金，2018。營養學第五版。華格納企業有限公司，台中。
黃登福、陳南宏，2007。熱帶性海魚毒。科學發展月刊 420: 13-16
羅嘉豪，2009。台灣海域鯙科魚類之分子類緣關係與生殖生物學之研究 國立臺灣海洋大學，基隆市。
蕭寧馨，2018。食品營養概論第四版。時新出版有限公司，台北。
歐秋屏，2007。台灣東部海域黴身裸胸鯙及白斑裸胸鯙之生殖生物學研究。國立臺灣海洋大學，基隆市。
郭百濼，2023。臺灣箱魨科之 PCR-RFLP 魚種辨別及肝臟中菟葵毒和維生素 A 含量之探討。國立臺灣海洋大學，基隆市。
邵廣昭，2024。台灣魚類資料庫。網路電子版 http://fishdb.sinica.edu.tw，台北。
簡崧舜，2023。臺灣鰻形目鯙科魚類懸垂骨、鰓蓋、鰓弓系硬骨形態學之比較研究。國立臺灣海洋大學，基隆市。
Alles, A. J., and Sulik, K. K. (1989). Retinoic‐acid‐induced limb‐reduction defects: Perturbation of zones of programmed cell death as a pathogenetic mechanism. Teratology, 40(2), 163-171.
Ardigier, G., Drouet, G., and Haro, L. d. (2010). Poisoning after ingestion of Mediterranean greater amberjack liver: Hypervitaminosis A clinical feature. Presse Médicale, 39(7/8), 833-836.
Aşkın, Ö., Uzunçakmak, T., Altunkalem, N., and Tüzün, Y. (2021). Vitamin deficiencies/hypervitaminosis and the skin. Clin Dermatol, 39(5), 847-857.
Aydelotte, M. B. (1963). Vitamin A deficiency in chickens. British Journal of Nutrition, 17(1), 205-210.
Babatola, A. O., Olatunya, O. S., Ogundare, E. O., Ajite, A. B., Oluwayemi, I. O., Thomas, A. A., Taiwo, A. B., Fatunla, O. A., Komolafe, A. K., and Alfred, A. (2019). Acute hypervitaminosis A misdiagnosed as malaria in a 7-year-old Nigerian boy. International Medical Case Reports Journal, 213-216.
Ballard, J. W. O., and Rand, D. M. (2005). The population biology of mitochondrial DNA and its phylogenetic implications. Annual Review of Ecology, Evolution, and Systematics., 36, 621-642.
Beltrán-de-Miguel, B., Estévez-Santiago, R., and Olmedilla-Alonso, B. (2015). Assessment of dietary vitamin A intake (retinol, α-carotene, β-carotene, β-cryptoxanthin) and its sources in the National Survey of Dietary Intake in Spain (2009–2010). International Journal of Food Sciences and Nutrition, 66(6), 706-712.
Benbrook, D., Lernhardt, E., and Pfahl, M. (1988). A new retinoic acid receptor identified from a hepatocellular carcinoma. Nature, 333(6174), 669-672.
Benoit, E., Legrand, A. M., and Dubois, J. M. (1986). Effects of ciguatoxin on current and voltage clamped frog myelinated nerve fibre.Toxicon, 24(4), 357-364.
Benoit, E. and Legrand, A.M. (1994). Gambiertoxin‐induced modifications of the membrane potential of myelinated nerve fibres. Memoirs of the Queensland Museum, 34: 461–464.
Bidlack, W. R. (1994). The retinoids: Biology, chemistry and medicine. Journal of the American College of Nutrition, 13(6), 675–676.
Birinyi-Strachan, L. C., Davies, M. J., Lewis, R. J., and Nicholson, G. M. (2005). Neuroprotectant effects of iso-osmolar D-mannitol to prevent Pacific ciguatoxin-1 induced alterations in neuronal excitability: A comparison with other osmotic agents and free radical scavengers. Neuropharmacology, 49(5), 669-686.
Blomhoff, R., Helgerud, P., Rasmussen, M., Berg, T., and Norum, K. R. (1982). In vivo uptake of chylomicron [3H] retinyl ester by rat liver: evidence for retinol transfer from parenchymal to nonparenchymal cells. Proceedings of the National Academy of Sciences, 79(23), 7326-7330.
Blomhoff, R., Green, M. H., Green, J. B., Berg, T., and Norum, K. R. (1991). Vitamin A metabolism: new perspectives on absorption, transport, and storage. Physiological Reviews, 71(4), 951-990.
Bookout, A. L., Jeong, Y., Downes, M., Ruth, T. Y., Evans, R. M., and Mangelsdorf, D. J. (2006). Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network. Cell, 126(4), 789-799.
Brand, N., Petkovich, M., Krust, A., Chambon, P., de Thé, H., Marchio, A., Tiollais, P., and Dejean, A. (1988). Identification of a second human retinoic acid receptor. Nature, 332(6167), 850-853.
Chan, T. Y. (2017). Regional variations in the risk and severity of ciguatera caused by eating moray eels. Toxins, 9(7), 201.
Chang, C. H., Lu, C. W., Chung, W. H., and Ho, H. C. (2018). Acute fish liver intoxication induced blisters formation and generalized skin peeling. Clinical Toxicology, 56(2), 146-148.
Chawla, A., Repa, J. J., Evans, R. M., and Mangelsdorf, D. J. (2001). Nuclear receptors and lipid physiology: Opening the X-files. Science, 294(5548), 1866-1870.
Chen, H. M., Shao, K. T., and Chen, C. T. (1994). A review of the muraenid eels (Family Muraenidae) from Taiwan with descriptions of twelve new records. Zoological Studies, 33(1), 44-64.
Chen, J. B., Pan, H. H., and Hwang, D. F. (2001). Myoglobinuric acute renal failure following cardioversion in a boxfish poisoning patient. Nephrology Dialysis Transplantation, 16(8), 1700-1701.
Chinain M, Gatti CMI, Darius HT, Quod JP, and Tester PA. (2021). Ciguatera poisonings: A global review of occurrences and trends. Harmful Algae. 102, 101873.
Chiu, Y., Lai, M., Ho, J., and Chen, J. (1999). Acute fish liver intoxication: Report of three cases. Changgeng Yi Xue Za Zhi, 22(3), 468-473.
Chytil, F., and Ong, D. E. (1979). Cellular vitamin A binding proteins. Vitamins and Hormones, 36, 1-32.
Clagett-Dame, M., and DeLuca, H. F. (2002). The role of vitamin A in mammalian reproduction and embryonic development. Annual Review of Nutrition, 22(1), 347-381.
Cohlan, S. Q. (1953). Excessive intake of vitamin A as a cause of congenital anomalies in the rat. Science, 117(3046), 535-536.
Cooper, A. D. (1997). Hepatic uptake of chylomicron remnants. Journal of Lipid Research, 38(11), 2173-2192.
Czuba, L. C., Zhong, G., Yabut, K. C., and Isoherranen, N. (2020). Analysis of vitamin A and retinoids in biological matrices. Methods Enzymol, 637, 309-340.
D’Ambrosio, D. N., Clugston, R. D., and Blaner, W. S. (2011). Vitamin A metabolism: An update. Nutrients, 3(1), 63-103.
Darwish, W. S., Ikenaka, Y., Morshdy, A. E., Eldesoky, K. I., Nakayama, S., Mizukawa, H., and Ishizuka, M. (2016). β-carotene and retinol contents in the meat of herbivorous ungulates with a special reference to their public health importance. Journal of Veterinary Medical Science, 78(2), 351-354.
De Luca, L., and Wolf, G. (1972). Mechanism of action of vitamin A in differentiation of mucus-secreting epithelia. Journal of Agricultural and Food Chemistry, 20(3), 474-476.
Di Masi, A., De Marinis, E., Ascenzi, P., and Marino, M. (2009). Nuclear receptors CAR and PXR: Molecular, functional, and biomedical aspects. Molecular Aspects of Medicine, 30(5), 297-343.
Dragovic-Uzelac, V., Levaj, B., Mrkic, V., Bursac, D., and Boras, M. (2007). The content of polyphenols and carotenoids in three apricot cultivars depending on stage of maturity and geographical region. Food Chemistry, 102(3), 966-975.
Eisenblatter, A., Lewis, R., Dorfler, A., Forster, C. and Zimmermann, K. (2017). Brain mechanisms of abnormal temperature perception in cold allodynia induced by ciguatoxin. Annals of Neurology, 81(1), 104–116.
Elmadfa, I., and Majchrzak, D. (1998). Carotinoide and vitamin A in fischproben. European Journal of Nutrition, 37, 207-210.
Fey, D. P. (2001). Differences in temperature conditions and somatic growth rate of larval and early juvenile spring‐spawned herring from the Vistula Lagoon, Baltic Sea manifested in the otolith to fish size relationship. Journal of Fish Biology, 58(5), 1257-1273.
Fortuna, V. A., Trugo, L. C., and Borojevic, R. (2001). Acyl-CoA: Retinol acyltransferase (ARAT) and lecithin: Retinol acyltransferase (LRAT) activation during the lipocyte phenotype induction in hepatic stellate cells. The Journal of Nutritional Biochemistry, 12(11), 610-621.
Friedman, M. A., Fernandez, M., Backer, L. C., Dickey, R. W., Bernstein, J., Schrank, K., Kibler, S., Stephan, W., Gribble, M. O., Bienfang, P., Bowen, R. E., Degrasse, S., Flores Quintana, H. A., Loeffler, C. R., Weisman, R., Blythe, D., Berdalet, E., Ayyar, R., Clarkson-Townsend, D., Swajian, K., Benner, R., Brewer, T., and Fleming, L. E. (2017). An updated review of ciguatera hish poisoning: clinical, epidemiological, environmental, and public health management. Marine Drugs, 15(3), 72.
Gatti, C., Oelher, E., and Legrand, A. M. (2008). Severe seafood poisoning in French Polynesia: A retrospective analysis of 129 medical files. Toxicon, 51(5), 746-753.
Ghiaroni, V., Fuwa, H., Inoue, M., Sasaki, M., Miyazaki, K., Hirama, M., Yasumoto, T., Paolo, R. G., Scalera, G., and Bigiani, A. (2006). Effect of ciguatoxin 3C on voltage‐gated Na+ and K+ currents in mouse taste cells. Chemical Senses, 31, 673–680.
Giguere, V., Ong, E. S., Segui, P., and Evans, R. M. (1987). Identification of a receptor for the morphogen retinoic acid. Nature, 330(6149), 624-629.
Goodman, D. S. (1984). Vitamin A and retinoids in health and disease. New England Journal of Medicine, 310(16), 1023-1031.
Green, A. S., and Fascetti, A. J. (2016). Meeting the vitamin A requirement: The efficacy and lmportance of β-carotene in animal species. The Scientific World Journal, 2016, 7393620.
Harrison, E. H. (2012). Mechanisms involved in the intestinal absorption of dietary vitamin A and provitamin A carotenoids. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids, 1821(1), 70-77.
Hebuterne, X., Wang, X. D., Smith, D. E., Tang, G., and Russell, R. M. (1996). In vivo biosynthesis of retinoic acid from beta-carotene involves and excentric cleavage pathway in ferret intestine. Journal of Lipid Research, 37(3), 482-492.
Hogg, R.C., Lewis, R.J., & Adams, D.J. (2002). Ciguatoxin‐induced oscillations in membrane potential and action potential firing in rat parasympathetic neurons. European Journal Neuroscience , 16(2), 242‐248.
Hoyos, B., Imam, A., Korichneva, I., Levi, E., Chua, R., and Hammerling, U. (2002). Activation of c-Raf kinase by ultraviolet light: Regulation by retinoids. Journal of Biological Chemistry, 277(26), 23949-23957
Homma, Y., Otani, N., and Ishimatsu, S. (2015). A case report of acute vitamin A intoxication due to ocean perch liver ingestion. The Journal of Emergency Medicine,49(1), 15-17.
Huang, Y., Liu, A., Liu, L., Wang, B., and Liang, G. (2020). The association between vitamin deficiency and otolaryngologic diseases: A therapeutic target. Medical Hypotheses, 135, 109448
Huang, W. C., Shiao, J. C., and Liao, T. Y. (2017). New record of the enigmatic moray Gymnothorax enigmaticus McCosker and Randall, 1982 (Anguilliformes: Muraenidae) from Taiwan. Platax, 14, 89-95.
Huang, W. C., Yu, Y. H., and Chou, M. T. (2021). A newly recorded moray Echidna rhodochilus Bleeker, 1863 (Anguilliformes: Muraenidae) from an estuary in Northeastern Taiwan. Platax, 2021, 43-51.
Huang, W. C., Mohapatra, A., Thu, P. T., Chen, H. M., and Liao, T. Y. (2020). A review of the genus Strophidon (Anguilliformes: Muraenidae), with description of a new species. Journal of Fish Biology, 97(5), 1462-1480.
Hubalkova, Z., Kralik, P., Tremlova, B., and Rencova, E. (2007). Methods of gadoid fish species identification in food and their economic impact in the Czech Republic: A review. Veterinarni Medicina, 52(7), 273.
Ikehara, T., Kuniyoshi, K., Oshiro, N., and Yasumoto, T. (2017). Biooxidation of ciguatoxins leads to species-specific toxin profiles. Toxins (Basel), 9(7), 205.
Inomata, T., Kiuchi, A., Yoshida, T., Hisamatsu, S., Takizawa, A., Kashiwazaki, N., Akahori, F., and Ninomiya, H. (2005). Hypervitaminosis A resulting in DNA aberration in fetal transgenic mice (MutaTM Mouse). Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 586(1), 58-67.
Innis, M., and Gelfand, D. (1999). Optimization of PCR: Conversations between Michael and David. In PCR applications : Protocols for functional Genomics. (ed. by Innis, M. A., Gelfand, D. H., Sninsky, J. J. and White, T. J.), Academic Press, New York, USA. pp. 3-12
Jacques, E. A., Buschmann, R. J., and Layden, T. J. (1979). The histopathologic progression of vitamin A-induced hepatic injury. Gastroenterology, 76(3), 599-602.
Kanai, M., Raz, A., and Goodman, D. S. (1968). Retinol-binding protein: the transport protein for vitamin A in human plasma. The Journal of Clinical Investigation, 47(9), 2025-2044.
Karrer, P. (1934). The chemistry of vitamins A and C. Chemical Reviews, 14(1), 17-30.
Kawase, I., Mori, J., and Yokoi, N. (2022). Vitamin A deficiency manifested as conjunctival hyperemia due to a limited food repertoire. Pediatrics International, 64(1), e14870.
Kocher, T. D., Thomas, W. K., Meyer, A., Edwards, S. V., Pääbo, S., Villablanca, F. X., and Wilson, A. C. (1989). Dynamics of mitochondrial DNA evolution in animals: amplification and sequencing with conserved primers. Proceedings of the 2012 Academy of Sciences, 86(16), 6196-6200.
La Frano, M. R., and Burri, B. J. (2014). Analysis of retinol, 3‐hydroxyretinol and 3, 4‐didehydroretinol in North American farm‐raised freshwater fish liver, muscle and feed. Aquaculture Nutrition, 20(6), 722-730.
Lavrov, D. V., Forget, L., Kelly, M., and Lang, B. F. (2005). Mitochondrial genomes of two demosponges provide insights into an early stage of animal evolution. Molecular Biology and Evolution, 22(5), 1231-1239.
Lakra, W. S., Goswami, M., and Gopalakrishnan, A. (2009). Molecular identification and phylogenetic relationships of seven Indian Sciaenids (Pisces: Perciformes, Sciaenidae) based on 16S rRNA and cytochrome c oxidase subunit I mitochondrial genes. Molecular Biology Reports, 36, 831-839.
Leicht, E., Strunz, J., von Seebach, H. B., Meiser, R. J., and Mäusle, E. (1973). Acute vitamin A intoxication with hemolytic anemia, hypercalcemia and toxic hepatosis. Medizinische Klinik [Urban und Schwarzenberg], 68(2), 54-59.
Lerner, A. J., Gustaw‐Rothenberg, K., Smyth, S., and Casadesus, G. (2012). Retinoids for treatment of Alzheimer's disease. Biofactors, 38(2), 84-89.
Lewis, R. J. (2001). The changing face of ciguatera. Toxicon, 39(1), 97-106.
Lewis, R. J., Sellin, M., Poli, M. A., Norton, R. S., MacLeod, J. K., and Sheil, M. M. (1991). Purification and characterization of ciguatoxins from moray eel (Lycodontis javanicus, Muraenidae). Toxicon, 29(9), 1115-1127.
Litaker, R. W., Vandersea, M. W., Faust, M. A., Kibler, S. R., Nau, A. W., Holland, W. C., Chinain, M., Holmes, M. J., and Tester, P. A. (2010). Global distribution of ciguatera causing dinoflagellates in the genus Gambierdiscus. Toxicon, 56(5), 711-730.
Loeffler, C. R., Abraham, A., Stopa, J. E., Quintana, H. A. F., Jester, E. L. E., La Pinta, J., Deeds, J., Benner, R. A., and Adolf, J. (2022). Ciguatoxin in Hawai'i: Fisheries forecasting using geospatial and environmental analyses for the invasive Cephalopholis argus (Epinephelidae). Environmental Research, 207, 112164.
Mahoney, G. L., Larcombe, P. J., Ling, J., and Ashok Kumar, A. (2022). Vitamin A deficiency in avoidant restrictive food intake disorder. Journal of Paediatrics and Child Health, 58(10), 1899-1900.
Maiani, G., Periago Castón, M. J., Catasta, G., Toti, E., Cambrodón, I. G., Bysted, A., Granado-Lorencio, F., Olmedilla-Alonso, B., Knuthsen, P., Valoti, M., Bohm, V., Mayer-Miebach, E., Behsnilian, D and Schlemmer, U. (2009). Carotenoids: actual knowledge on food sources, intakes, stability and bioavailability and their protective role in humans. Molecular Nutrition and Food Research, 53(S2), 194-218.
Mangelsdorf, D. J., and Evans, R. M. (1995). The RXR heterodimers and orphan receptors. Cell, 83(6), 841-850.
Mattei, C., Molgó, J., Marquais, M., Vernoux, J.-P., and Benoit, E. (1999). Hyperosmolar D-mannitol reverses the increased membrane excitability and the nodal swelling caused by Caribbean ciguatoxin-1 in single frog myelinated axons. Brain Research, 847(1), 50-58.
McCaffery, P., Mey, J., and Dräger, U. C. (1996). Light-mediated retinoic acid production. Proceedings of the National Academy of Sciences, 93(22), 12570-12574.
McCosker, J. E., and Stewart, A. L. (2006). Additions to the New Zealand marine eel fauna with the description of a new moray, Anarchias supremus (Teleostei: Muraenidae), and comments on the identity of Gymnothorax griffini Whitley and Phillips. Journal of the Royal Society of New Zealand, 36(2), 83-95.
McCullough, F. S. W., Northrop-Clewes, C. A., and Thurnham, D. I. (1999). The effect of vitamin A on epithelial integrity. Proceedings of the Nutrition Society, 58(2), 289-293.
Moore, R. E., and Bartolini, G. (1981). Structure of palytoxin. Journal of the American Chemical Society, 103(9), 2491-2494.
Moore, T., and Wang, Y. (1945). Hypervitaminosis A. Biochemical Journal, 39(3), 222.
Morriss‐Kay, G. M., and Sokolova, N. (1996). Embryonic development and pattern formation. The FASEB journal, 10(9), 961-968.
Mottola, A., Marchetti, P., Ciccarese, G., Terio, V., Sinisi, C., and Di Pinto, A. (2020). Arcobacter species detection in Italian composite foods. LWT, 134, 110161.
Muenter, M. D., Perry, H. O., and Ludwig, J. (1971). Chronic vitamin A intoxication in adults: Hepatic, neurologic and dermatologic complications. The American Journal of Medicine, 50(1), 129-136.
Murata, M., Legrand, A. M., Ishibashi, Y., and Yasumoto, T. (1989). Structures of ciguatoxin and its congener. Journal of the American Chemical Society, 111(24), 8929-8931.
Mustapa, N. I., Yong, H. L., Lee, L. K., Lim, Z. F., Lim, H. C., Teng, S. T., Luo, Z., Gu, H., Leaw, C. P., and Lim, P. T. (2019). Growth and epiphytic behavior of three Gambierdiscus species (Dinophyceae) associated with various macroalgal substrates. Harmful Algae, 89, 101671.
Nakahara, H., Sakami, T., Chinain, M., and Ishida, Y. (1996). The role of macroalgae in epiphytism of the toxic dinoflagellate Gambierdiscus toxicus (Dinophyceae).Phycological Research, 44(2), 113-117.
Nelson, J. S., Grande, T. C., and Wilson, M. V. (2016). Fishes of the World. John Wiley and Sons Inc., Hoboken, New Jersey. 457-458
Newcomer, M. E., and Ong, D. E. (2000). Plasma retinol binding protein: structure and function of the prototypic lipocalin. Biochimica et Biophysica Acta (BBA)-Protein Structure and Molecular Enzymology, 1482(1-2), 57-64.
Niederreither, K., and Dollé, P. (2008). Retinoic acid in development: Towards an integrated view. Nature Reviews Genetics, 9(7), 541-553.
Ochoa, W. F., Torrecillas, A., Fita, I., Verdaguer, N., Corbalán-García, S., and Gomez-Fernandez, J. C. (2003). Retinoic acid binds to the C2-domain of protein kinase Cα. Biochemistry, 42(29), 8774-8779.
Ollilainen, V., Heinonen, M., Linkola, E., Varo, P., and Koivistoinen, P. (1989). Carotenoids and retinoids in Finnish foods: dairy products and eggs. Journal of Dairy Science, 72(9), 2257-2265.
Omori, M., and Chytil, F. (1982). Mechanism of vitamin A action. Gene expression in retinol-deficient rats. Journal of Biological Chemistry, 257(23), 14370-14374.
Palace, V. P., Khaper, N., Qin, Q., and Singal, P. K. (1999). Antioxidant potentials of vitamin A and carotenoids and their relevance to heart disease. Free Radical Biology and Medicine, 26(5-6), 746-761.
Palafox, N.A., Jain, L.G., Pinano, A.Z., Gulick, T.M., Williams, R.K. and Schatz, I.J. (1988). Successful treatment of ciguatera fish poisoning with intravenous mannitol. The Journal of the American Medical Association, 259(18), 2740–2742.
Parsons, M. L., Aligizaki, K., Bottein, M. Y. D., Fraga, S., Morton, S. L., Penna, A., and Rhodes, L. (2012). Gambierdiscus and Ostreopsis: reassessment of the state of knowledge of their taxonomy, geography, ecophysiology, and toxicology. Harmful Algae, 14, 107-129.
Paun, O., and Schönswetter, P. (2012). Amplified fragment length polymorphism: An invaluable fingerprinting technique for genomic, transcriptomic, and epigenetic studies. In: Plant DNA Fingerprinting and Barcoding: Methods and Protocols, (ed. by Sucher, N. J., Hennell, J. R., Carles, M. C.), Humana apress, New Jersey, USA, pp. 75-87.
Perusek, L., and Maeda, T. (2013). Vitamin A derivatives as treatment options for retinal degenerative diseases. Nutrients, 5(7), 2646-2666.
Penniston, K. L., and Tanumihardjo, S. A. (2006). The acute and chronic toxic effects of vitamin A. The American Journal of Clinical Nutrition, 83(2), 191-201.
Petkovich, M., Brand, N. J., Krust, A., and Chambon, P. (1987). A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature, 330(6147), 444-450.
Quick, T. C., and Ong, D. E. (1990). Vitamin A metabolism in the human intestinal Caco-2 cell line. Biochemistry, 29(50), 11116-11123.
Quod, J., and Turquet, J. (1996). Ciguatera in Reunion Island (SW Indian Ocean): epidemiology and clinical patterns. Toxicon, 34(7), 779-785.
Rahman, M. T., Uddin, M. S., Sultana, R., Moue, A., and Setu, M. (2013). Polymerase chain reaction (PCR): A short review. Anwer Khan Modern Medical College Journal, 4(1), 30-36.
Ramos-Miras, J. J., Sanchez-Muros, M. J., Morote, E., Torrijos, M., Gil, C., Zamani-Ahmadmahmoodi, R., and Rodriguez Martin, J. A. (2019). Potentially toxic elements in commonly consumed fish species from the western Mediterranean Sea (Almeria Bay): Bioaccumulation in liver and muscle tissues in relation to biometric parameters. Science of The Total Environment, 671, 280-287.
Raz, A. M. I. R. A. M., and Goodman, D. S. (1969). The interaction of thyroxine with human plasma prealbumin and with the prealbumin-retinol-binding protein complex. Journal of Biological Chemistry, 244(12), 3230-3237.
Rothman, K. J., Moore, L. L., Singer, M. R., Nguyen, U. S. D., Mannino, S., and Milunsky, A. (1995). Teratogenicity of high vitamin A intake. New England Journal of Medicine, 333(21), 1369-1373
Russell, R. M., Boyer, J. L., Bagheri, S. A., and Hruban, Z. (1974). Hepatic injury from chronic hypervitaminosis A resulting in portal hypertension and ascites. New England Journal of Medicine, 291(9), 435-440.
Saari, J. C. (2016). Vitamin A and vision. In: The Biochemistry of Retinoid Signaling II: The Physiology of Vitamin A-Uptake, Transport, Metabolism and Signaling (ed. by Asson-Batres, M. A., Rochette-Egly, C), Springer Netherlands, Berlin, DEU, 231-259.
Saitou, N., and Nei, M. (1987). The neighbor-joining method: a new method for reconstructing phylogenetic trees. Molecular Biology and Evolution, 4(4), 406-425.
Saitou, N. (1988). Property and efficiency of the maximum likelihood method for molecular phylogeny. Journal of Molecular Evolution, 27, 261-273.
Sanchez-Henao, A., Garcia-Alvarez, N., Sergent, F. S., Estevez, P., Gago-Martinez, A., Martin, F., Ramos-Sosa, M., Fernandez, A., Diogene, J., and Real, F. (2020). Presence of CTXs in moray eels and dusky groupers in the marine environment of the Canary Islands. Aquatic Toxicology, 221, 105427.
Schadt, E. E., Sinsheimer, J. S., and Lange, K. (1998). Computational advances in maximum likelihood methods for molecular phylogeny. Genome Research, 8(3), 222-233.
Schmitt, C., Domangé, B., Torrents, R., de Haro, L., and Simon, N. (2020). Hypervitaminosis A following the ingestion of fish liver: Report on 3 cases from the Poison Control Center in Marseille. Wilderness and Environmental Medicine, 31(4), 454-456.
Schulz-Mirbach, T., Ladich, F., Plath, M., and Hess, M. (2019). Enigmatic ear stones: what we know about the functional role and evolution of fish otoliths. Biological Reviews, 94(2), 457-482.
Semba, R. D. (2012). On the ‘discovery’of vitamin A. Annals of Nutrition and Metabolism, 61(3), 192-198.
Silverman, A. K., Ellis, C. N., and Voorhees, J. J. (1987). Hypervitaminosis A syndrome: A paradigm of retinoid side effects. Journal of the American Academy of Dermatology, 16(5), 1027-1039.
Smith, D. G., Bogorodsky, S. V., Mal, A. O., and Alpermann, T. J. (2019). Review of the moray eels (Anguilliformes: Muraenidae) of the Red Sea, with description of a new species. Zootaxa, 4704(1), zootaxa-4704.
Sneath, P. H. (1995). Thirty years of numerical taxonomy. Systematic Biology, 44(3), 281-298.
Song, S. L., YONG, H., LOH, K., Lim, P. E., Then, A. Y. H., and Eamsobhana, P. (2018). Mitogenome of Gymnothorax minor and Phylogenetic Relationship with Its Congeners and Related Genera (Anguilliformes: Muraenidae). Sains Malaysiana, 47(10), 2519-2531.
Tamura, K., Stecher, G., and Kumar, S. (2021). MEGA11: molecular evolutionary genetics analysis version 11. Molecular Biology and Evolution, 38(7), 3022-3027.
Tapiero, H., Townsend, D. M., and Tew, K. D. (2004). The role of carotenoids in the prevention of human pathologies. Biomedicine and Pharmacotherapy, 58(2), 100-110.
Taniyama, S., Arakawa, O., Terada, M., Nishio, S., Takatani, T., Mahmud, Y., and Noguchi, T. (2003). Ostreopsis sp., A possible origin of palytoxin (PTX) in parrotfish Scarus ovifrons. Toxicon, 42(1), 29-33.
Teletchea, F. (2009). Molecular identification methods of fish species: reassessment and possible applications. Reviews in Fish Biology and Fisheries, 19, 265-293.
Tsai, W.-L., Chen, H.-M., Hsieh, C.-H., Lin, W.-F., and Hwang, D.-F. (2009). A potential methodology for differentiation of ciguatgoxin-carrying species of moray eel. Food Control, 20(6), 575-579.
Tuffley, C., and Steel, M. (1997). Links between maximum likelihood and maximum parsimony under a simple model of site substitution. Bulletin of Mathematical Biology, 59, 581-607.
Usami, M., Satake, M., Ishida, S., Inoue, A., Kan, Y., and Yasumoto, T. (1995). Palytoxin analogs from the dinoflagellate Ostreopsis siamensis. Journal of the American Chemical Society, 117(19), 5389-5390.
Vieira, M., and Saraiva, M. J. (2014). Transthyretin: a multifaceted protein. Biomolecular Concepts, 5(1), 45-54.
Wang, D. Z., Xin, Y. H., and Wang, M. H. (2022). Gambierdiscus and its associated toxins: A mini review. Toxins (Basel), 14(7), 485.
Wisse, E., De Zanger, R., Charels, K., Van Der Smissen, P., and McCuskey, R. (1985). The liver sieve: considerations concerning the structure and function of endothelial fenestrae, the sinusoidal wall and the space of disse. Hepatology, 5(4), 683-692.
Xue, Y., Shen, S. Q., Jui, J., Rupp, A. C., Byrne, L. C., Hattar, S., Flannery, J. G., Corbo, J. C., and Kefalov, V. J. (2015). CRALBP supports the mammalian retinal visual cycle and cone vision. The Journal of Clinical Investigation, 125(2), 727-738.
Xu, Y., He, X., Lee, W. H., Chan, L. L., Lu, D., Wang, P., Tao, X., Li, H., and Yu, K. (2021). Ciguatoxin-producing dinoflagellate Gambierdiscus in the Beibu Gulf: First report of toxic Gambierdiscus in Chinese waters. Toxins, 13(9), 643.
Yasumoto, T. (2001). The chemistry and biological function of natural marine toxins. Chemical Record, 1(3), 228-242.
Yim, S. K., Kim, S. W., and Lee, S. T. (2021). Efficient stool collection methods for evaluating the diarrhea score in mouse diarrhea models. In Vivo, 35(4), 2115-2125.
Zhong, M., Kawaguchi, R., Kassai, M., and Sun, H. (2012). Retina, retinol, retinal and the natural history of vitamin A as a light sensor. Nutrients, 4(12), 2069-2096.
Zelent, A., Krust, A., Petkovich, M., Kastner, P., and Chambon, P. (1989). Cloning of murine α and β retinoic acid receptors and a novel receptor γ predominantly expressed in skin. Nature, 339(6227), 714-717.
Zheng, W. J., DeMattei, J. A., Wu, J. P., Duan, J. J. W., Cook, L. R., Oinuma, H., and Kishi, Y. (1996). Complete relative stereochemistry of maitotoxin. Journal of the American Chemical Society, 118(34), 7946-7968.