Propiconazole

Propiconazole is an orally active N-substituted triazole Propiconazole with antifungal activity. Propiconazole is a hepatocarcinogen and has certain reproductive and developmental toxicity in experimental animals^[1][2].

Propiconazole (0.25-100μM; 48h) induced glutathione-S-transferase (GSTα) protein levels and increased the levels of thiobarbituric acid reactive substances (TBARS) in AML12 cells^[1]. After Propiconazole (0-160μM; 3-72h) treatment of HepG2 cells, the cells induced morphological changes through oxidative stress and TGF-β/Smad pathways, with a decrease in E-cadherin and an increase in vimentin and Snail^[2]. Propiconazole (1-20μM; 24h) treatment of AML12 hepatocytes mediated alterations in the mevalonate/cholesterol pathway and caused increased cell proliferation through dysregulation of the cholesterol pathway. Propiconazole increased Ras farnesylation, altered Ras membrane localization, and activated downstream signaling effects, increasing Erk1/2 phosphorylation^[3].

Propiconazole (10, 75, and 150mg/kg; po; 14 days) fed to healthy mice induced an increase in cytochrome P450 gene expression and related enzyme activities in the liver of mice^[4]. In a diet-induced obese mouse model, Propiconazole (0.04-100mg/kg; 10 weeks) dose-dependently increased liver weight and triglyceride levels in mice, and high doses induced signs of liver inflammation^[5]. Propiconazole (5.0mg/kg; 96h) induced oxidative damage in zebrafish embryos, manifested by increased ROS and MDA levels and altered antioxidant enzyme activities^[6].

References:
[1]. Nesnow S, Grindstaff R D, Lambert G, et al. Propiconazole increases reactive oxygen species levels in mouse hepatic cells in culture and in mouse liver by a cytochrome P450 enzyme mediated process[J]. Chemico-biological interactions, 2011, 194(1): 79-89.
[2]. Kwon H C, Sohn H, Kim D H, et al. In vitro and in vivo study on the toxic effects of Propiconazole fungicide in the pathogenesis of liver fibrosis[J]. Journal of Agricultural and Food Chemistry, 2021, 69(26): 7399-7408.
[3]. Murphy L A, Moore T, Nesnow S. Propiconazole-enhanced hepatic cell proliferation is associated with dysregulation of the cholesterol biosynthesis pathway leading to activation of Erk1/2 through Ras farnesylation[J]. Toxicology and applied pharmacology, 2012, 260(2): 146-154.
[4]. Sun G, Thai S F, Tully D B, et al. Propiconazole-induced cytochrome P450 gene expression and enzymatic activities in rat and mouse liver[J]. Toxicology letters, 2005, 155(2): 277-287.
[5]. Attema B, Kummu O, Krutáková M, et al. The fungicide propiconazole induces hepatic steatosis and activates PXR in a mouse model of diet-induced obesity[J]. Archives of Toxicology, 2024: 1-19.
[6]. Zhao F, Cao F, Li H, et al. The effects of a short-term exposure to propiconazole in zebrafish (Danio rerio) embryos[J]. Environmental Science and Pollution Research, 2020, 27: 38212-38220.

Propiconazole是一种口服有效的N-取代三唑类丙环唑，具有抗真菌活性。Propiconazole是一种肝致癌物，对实验动物有一定的生殖和发育毒性^[1][2]。

Propiconazole（0.25-100μM；48h）诱导AML12细胞中谷胱甘肽-S-转移酶（GSTα）蛋白水平，并增加硫代巴比妥酸反应物质（TBARS）水平^[1]。Propiconazole（0-160μM；3-72h）处理HepG2细胞后，细胞通过氧化应激和TGF-β/Smad通路诱导形态学变化，E-钙粘蛋白减少，波形蛋白和Snail增加^[2]。Propiconazole（1-20μM；24h）处理AML12肝细胞介导甲羟戊酸/胆固醇通路的改变，并通过胆固醇通路失调导致细胞增殖增加。Propiconazole增加Ras法尼基化，改变Ras膜定位，并激活下游信号传导效应，增加Erk1/2磷酸化^[3]。

给健康小鼠喂食Propiconazole（10、75、150mg/kg；po；14d）可诱导小鼠肝脏细胞色素P450基因表达和相关酶活性增加^[4]。在饮食诱导的肥胖小鼠模型中，Propiconazole（0.04-100mg/kg；10周）剂量依赖性地增加小鼠的肝脏重量和甘油三酯水平，高剂量诱导肝脏炎症迹象^[5]。Propiconazole（5.0mg/kg；96h）可引起斑马鱼胚胎氧化损伤，表现为ROS和MDA水平升高，抗氧化酶活性改变^[6]。