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.