A mycotoxin with diverse biological activities
Citrinin is a mycotoxin inducing apoptosis and blocking tubulin polymerization and mitotic spindle assembly.
Citrinin is a mycotoxin originally isolated from P. citrinum that is also produced by a variety of other fungi that are found as contaminants in human foodstuffs and animal feeds.
In vitro: Previous study found that exposure of HEK293 cells to citrinin led to an arrest of cell cycle G2/M in a concentration-dependent increase. Citrinin treatment could also elevate the expression levels of p53 and p21 proteins, yet attenuate the signals of phosphorylated cell division cycle 2. Moreover, treating HEK293 with citrinin could increase both the value of mitotic index and the population of cells, indicating that arrest of citrinin -induced cell cycle occurred mainly during the mitotic phase [1].
In vivo: Previous study showed that citrinin acted as a nephrotoxin in all tested animal species, but its acute toxicity varied in different species. The 50% lethal dose for ducks is 57 mg/kg; for chickens it is 95 mg/kg; and for rabbits it is 134 mg/kg. In murine kidneys, citrinin could also synergistically act with ochratoxin A to depress RNA synthesis [2].
Clinical trial: Up to now, there is no clinical data reported.
Citrinin是一种霉菌毒素，可以诱导细胞凋亡，并阻断微管聚合和有丝分裂纺锤体组装。
Citrinin最初是从柠檬黄曲霉中分离出来的霉菌毒素，也由其他一些霉菌产生，并在人类食品和动物饲料中被发现。
体外研究：之前的研究发现，将HEK293细胞暴露于citrinin会导致浓度依赖性的G2/M细胞周期停滞。Citrinin处理也可以提高p53和p21蛋白的表达水平，但减弱磷酸化的细胞分裂周期2的信号。此外，将HEK293细胞用citrinin处理后，可以增加有丝分裂指数的值和细胞群的数量，表明citrinin诱导的细胞周期停滞主要发生在有丝分裂期间[1]。
体内研究：之前的研究显示，citrinin在所有测试的动物物种中都作为肾毒素作用，但其急性毒性因物种而异。在鸭子中，50％的致死剂量为57mg/kg;在鸡中为95mg/kg;在兔子中为134mg/kg。在小鼠肾中，citrinin也可以与赭曲霉毒素A协同作用，抑制RNA合成[2]。
临床试验：目前还没有报道任何临床数据。
参考文献:
[1] Chang CH, Yu FY, Wu TS, Wang LT, Liu BH.? Mycotoxin citrinin induced cell cycle G2/M arrest and numerical chromosomal aberration associated with disruption of microtubule formation in human cells. Toxicol Sci. 2011 Jan;119(1):84-92.
[2] J.? W. Bennett and M. Klich. Mycotoxins. Clin.Microbiol.Rev. 16(3), 497-516 (2003).
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