Alternariol is a mycotoxin produced by Alternariafungi, which is widely distributed in nature, particularly in grains, fruits, and vegetables under warm and humid conditions[1]. Alternariol inhibits the catalytic activity of topoisomerase I and IIα, interferes with normal DNA function, and exhibits cytotoxicity, genotoxicity, mutagenicity, and endocrine-disrupting effects[2]. While demonstrating toxicity, Alternariol has also been found to possess various biological activities such as antimicrobial, anti-HIV, anticancer, and immunomodulatory properties[3-4].
In vitro, treatment of human colon adenocarcinoma Caco-2 cells with Alternariol (15–60μM) for 24–48 hours induced cell cycle arrest in the S and G2/M phases, accompanied by loss of mitochondrial membrane potential and necrotic/apoptotic cell death[5]. Treatment of mouse RAW 264.7 macrophages with Alternariol (15–30μM) for 24–48 hours resulted in G2/M phase cell cycle arrest, along with abnormal nuclear morphology and polyploid formation[6].
In vivo, a single topical application of Alternariol (12.5–50μg per mouse) to the skin of Swiss albino mice for 24 hours induced an increase in skin fold thickness, edema, epidermal hyperplasia, and inflammatory responses[7]. Dietary exposure of C57BL/6 mice to Alternariol (5–20μg/kg) for 90 days caused dose-dependent hepatotoxicity, characterized by an increased liver index, elevated serum ALT and AST levels, and histopathological alterations in liver tissue[8].
References:
[1] Siegel D, Troyanov S, Noack J, et al. Acta Crystallogr Sect E Struct Rep Online. 2010 May 15;66(Pt 6):o1366.
[2] Saleh I, Zeidan R, Abu-Dieyeh M. The characteristics, occurrence, and toxicological effects of alternariol: a mycotoxin. Arch Toxicol. 2024 Jun;98(6):1659-1683.
[3] Islam MT, Martorell M, González-Contreras C, et al. An updated overview of anticancer effects of alternariol and its derivatives: underlying molecular mechanisms. Front Pharmacol. 2023 Mar 23;14:1099380.
[4] Ding J, Zhao J, Yang Z, et al. Microbial Natural Product Alternariol 5-O-Methyl Ether Inhibits HIV-1 Integration by Blocking Nuclear Import of the Pre-Integration Complex. Viruses. 2017 May 10;9(5):105.
[5] Fernández-Blanco C, Juan-García A, Juan C, et al. Alternariol induce toxicity via cell death and mitochondrial damage on Caco-2 cells. Food Chem Toxicol. 2016 Feb;88:32-9.
[6] Solhaug A, Holme JA, Haglund K, et al. Alternariol induces abnormal nuclear morphology and cell cycle arrest in murine RAW 264.7 macrophages. Toxicol Lett. 2013 May 10;219(1):8-17.
[7] Bansal M, Singh N, Alam S, et al. Alternariol induced proliferation in primary mouse keratinocytes and inflammation in mouse skin is regulated via PGE2/EP2/cAMP/p-CREB signaling pathway. Toxicology. 2019 Jan 15;412:79-88.
[8] Yu S, Shen X, Huang Y, et al. Mycotoxin Alternariol Exposure Promotes Endoplasmic Reticulum Stress-induced Hepatotoxicity to Exacerbate Chronic Liver Injury. Environ Pollut. 2025 Oct 6:127217.
Alternariol是一种由链格孢菌（Alternaria）产生的霉菌毒素，在自然界中广泛存在，尤其在潮湿温暖环境下的谷物、水果和蔬菜中[1]。Alternariol能够抑制拓扑异构酶I和IIα的催化活性，干扰DNA的正常功能，并具有细胞毒性、遗传毒性、诱变性及内分泌干扰作用[2]。Alternariol在表现出毒性的同时，也被发现具有抗微生物、抗HIV、抗癌以及免疫调节等多种生物活性[3-4]。
在体外，Alternariol (15–60μM) 处理人结肠腺癌Caco-2细胞24–48小时，可诱导细胞周期阻滞于S期和G2/M期，并引发线粒体膜电位损失及细胞坏死/凋亡性死亡[5]。Alternariol（15–30μM）处理小鼠RAW 264.7巨噬细胞24–48小时，可诱导细胞周期阻滞于G2/M期，并伴随细胞核形态异常和多倍体形成[6]。
在体内，Alternariol（12.5–50μg/只）单次局部涂抹处理皮肤受损的Swiss albino mice 24小时，可诱导皮肤双褶厚度增加和水肿，并引发表皮增生及炎症反应[7]。Alternariol（5–20μg/kg）通过饮食暴露持续90天处理C57BL/6小鼠，可诱导剂量依赖性肝损伤，表现为肝脏指数升高、血清转氨酶（ALT/AST）水平增加及肝组织病理学改变[8]。