Liu Xuan, Zhu Wenchao, Gai Xiaojun, Liu Shaoqing, Wang Chunxiao, Lv Lu, Wang Yanhua, Wang Xuejing, Lu Zeqi, Wang Zhixin
Yantai Academy of Agricultural Sciences, Yantai 265500, China.
State Key Laboratory for Quality and Safety of Agro-products, Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, Zhejiang, China.
Pestic Biochem Physiol. 2025 Nov;214:106640. doi: 10.1016/j.pestbp.2025.106640. Epub 2025 Aug 16.
The diamide insecticide cyantraniliprole (CYA) and the triazole fungicide difenoconazole (DIF) are frequently co-detected in bee-related matrices. However, the interactive effects of these compounds on honey bee (Apis mellifera L.) physiology remain insufficiently elucidated. Our results revealed that co-exposure to CYA and DIF elicited a pronounced acute synergistic toxicity. Biochemical assays demonstrated significant elevations in malondialdehyde (MDA) level, superoxide dismutase (SOD), and caspase-3 (CASP-3) activities across all treatments, with the most marked alterations occurring under co-exposure conditions. These data pointed to exacerbated oxidative stress and mitochondrial impairment when both pesticides were present concurrently. At the transcriptional level, notable dysregulation was observed in genes associated with apoptosis (caspase-1), detoxification (CYP4G11), immune modulation (dorsal-2), and lifespan regulation [vitellogenin (vtg)]. Notably, co-exposure intensified gene expression changes beyond those induced by single-pesticide treatments, underscoring a compound interaction that amplified cellular stress responses. These findings demonstrated that both CYA and DIF, especially in combination, disrupted critical physiological pathways in honey bees, compromising their detoxification capacity, immune integrity, and longevity. These insights not only unraveled key mechanistic underpinnings of pesticide mixture toxicity but also emphasized the urgent need for regulatory frameworks that address the mixture risks posed by agrochemical co-exposures in pollinator populations.
双酰胺类杀虫剂氰虫酰胺（CYA）和三唑类杀菌剂苯醚甲环唑（DIF）经常在与蜜蜂相关的基质中被共同检测到。然而，这些化合物对蜜蜂（西方蜜蜂）生理的交互作用仍未得到充分阐明。我们的结果表明，同时接触CYA和DIF会引发明显的急性协同毒性。生化分析表明，在所有处理组中，丙二醛（MDA）水平、超氧化物歧化酶（SOD）和半胱天冬酶-3（CASP-3）活性均显著升高，其中在同时接触条件下变化最为明显。这些数据表明，当两种农药同时存在时，氧化应激和线粒体损伤会加剧。在转录水平上，观察到与细胞凋亡（半胱天冬酶-1）、解毒（CYP4G11）、免疫调节（背侧-2）和寿命调节[卵黄原蛋白（vtg）]相关的基因存在明显失调。值得注意的是，同时接触加剧了基因表达的变化，超过了单一农药处理所诱导的变化，突出了一种放大细胞应激反应的化合物相互作用。这些发现表明，CYA和DIF，尤其是两者结合时，会破坏蜜蜂的关键生理途径，损害其解毒能力、免疫完整性和寿命。这些见解不仅揭示了农药混合物毒性的关键机制基础，还强调了迫切需要建立监管框架，以应对传粉者群体中农业化学品共同接触所带来的混合物风险。
