Citrinin

Citrinin is a mycotoxin with multiple biological activities produced by several fungal strains of the genera Penicillium, Aspergillus, and Monascus ^[1]. Citrinin is a natural contaminant in various foods that can cause serious adverse health problems and also has cytotoxic and genotoxic effects ^[2].

In vitro, Citrinin (30 μM) treated ESC-B5 cells for 24 hours can directly stimulate the production of ROS, thereby inducing NO production, leading to changes in mitochondrial membrane potential and the activation of caspase-9 and caspase-3 ^[3]. Citrinin (10, 20μM) treated hRPTEC cells for 3 and 30 days, significantly promoting cell mitotic spindle abnormalities, wound healing, cell migration and anchorage-dependent growth, and activating cancer and cell cycle-related signaling pathways ^[4]. Citrinin (40μM) treats embryonic cells and induces DNA damage, autophagy and mitochondrial dysfunction, adversely affecting early embryonic development during the first cleavage ^[5].

In vivo, Citrinin (1, 3, 5 mg/kg) was orally fed to female Wistar rats for 10 weeks, causing abnormal development of fetal weight, bones, and internal organs after pregnancy, resulting in severe teratogenic effects ^[6]. Citrinin (6.25mg/kg) treated male mice by intraperitoneal injection for 7 days, significantly increased the relative weight of testicles, epididymis, seminal vesicles and preputial glands, increased the number of abnormal sperm, and reduced the number of viable sperm ^[7].

References:
[1] Flajs D, Peraica M. Toxicological properties of citrinin[J]. Archives of Industrial Hygiene and Toxicology, 2009, 60(4): 457-464.
[2] Salah A, Bouaziz C, Prola A, et al. Citrinin induces apoptosis in human HCT116 colon cancer cells through endoplasmic reticulum stress[J]. Journal of Toxicology and Environmental Health, Part A, 2017, 80(23-24): 1230-1241.
[3] Chan W H. Citrinin induces apoptosis in mouse embryonic stem cells[J]. IUBMB life, 2008, 60(3): 171-179.
[4] Tsai J F, Wu T S, Huang Y T, et al. Exposure to Mycotoxin Citrinin Promotes Carcinogenic Potential of Human Renal Cells[J]. Journal of Agricultural and Food Chemistry, 2023, 71(48): 19054-19065.
[5] Huang Y L, Pan W L, Cai W W, et al. Exposure to citrinin induces DNA damage, autophagy, and mitochondria dysfunction during first cleavage of mouse embryos[J]. Environmental Toxicology, 2021, 36(11): 2217-2224.
[6] Singh N D, Sharma A K, Patil R D, et al. Effect of feeding graded doses of Citrinin on clinical and teratology in female Wistar rats[J]. 2014.
[7] Qingqing H, Linbo Y, Yunqian G, et al. Toxic effects of citrinin on the male reproductive system in mice[J]. Experimental and Toxicologic Pathology, 2012, 64(5): 465-469.

Citrinin是一种具有多种生物活性的霉菌毒素，由青霉属、曲霉属和红曲霉属的几种真菌菌株产生^[1]。Citrinin是各种食品的天然污染物，会产生严重的不良健康问题，还具有细胞毒性和基因毒性作用^[2]。

在体外，Citrinin（30μM）处理ESC-B5细胞24h，可以直接刺激ROS的产生，从而诱导NO产生，导致线粒体膜电位变化以及 caspase-9和caspase-3的激活^[3]。Citrinin（10, 20μM）处理hRPTEC细胞3天和30天，均显著促进细胞的有丝分裂纺锤体异常、伤口愈合、细胞迁移和贴壁依赖性生长，激活癌症和细胞周期相关的信号通路^[4]。Citrinin（40μM）处理胚胎细胞，诱导DNA损伤、自噬和线粒体功能障碍，对第一次卵裂期间的早期胚胎发育产生不利影响^[5]。

在体内，Citrinin（1, 3, 5mg/kg）通过口服饲喂雌性Wistar大鼠10周，导致大鼠怀孕后胎儿体重、骨骼、内脏均发育异常，产生了严重致畸作用^[6]。Citrinin（6.25mg/kg）通过腹腔注射处理雄性小鼠7天，显著增加睾丸、附睾、精囊和包皮腺的相对重量，增加异常精子数量，减少活精子数量^[7]。