Sulfonamide antibiotics, extensively used in human and veterinary therapy, accumulate in agroecosystem soils through livestock manure and sewage irrigation. However, the interaction between sulfonamides and rice plants remains unclear. This study investigated the transformation behavior and toxicity of sulfamethoxazole (SMX) and its main metabolite, N4-acetyl-sulfamethoxazole (NASMX) in rice. SMX and NASMX were rapidly taken up by roots and translocated acropetally. NASMX showed higher accumulating capacity, with NASMX concentrations up to 20.36 ± 1.98 μg/g (roots) and 5.62 ± 1.17 μg/g (shoots), and with SMX concentrations up to 15.97 ± 2.53 μg/g (roots) and 3.22 ± 0.789 μg/g (shoots). A total of 18 intermediate transformation products of SMX were identified by nontarget screening using Orbitrap-HRMS, revealing pathways such as deamination, hydroxylation, acetylation, formylation, and glycosylation. Notably, NASMX transformed back into SMX in rice, a novel finding. Transcriptomic analysis highlights the involvements of cytochrome P450 (CYP450), acetyltransferase (ACEs) and glycosyltransferases (GTs) in these biotransformation pathways. Moreover, exposure to SMX and NASMX disrupts TCA cycle, amino acid, linoleic acid, nucleotide metabolism, and phenylpropanoid biosynthesis pathways of rice, with NASMX exerting a stronger impact on metabolic networks. These findings elucidate the sulfonamides' metabolism, phytotoxicity mechanisms, and contribute to assessing food safety and human exposure risk amid antibiotic pollution.

中文翻译：

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磺胺甲恶唑和N4-乙酰磺胺甲恶唑在水稻中的转化过程及药害


磺酰胺类抗生素广泛用于人类和兽医治疗，通过牲畜粪便和污水灌溉在农业生态系统土壤中积累。然而，磺胺类药物与水稻之间的相互作用仍不清楚。本研究调查了磺胺甲恶唑（SMX）及其主要代谢物 N4-乙酰基磺胺甲恶唑（NASMX）在水稻中的转化行为和毒性。 SMX 和 NASMX 迅速被根吸收并转移到顶部。 NASMX表现出较高的积累能力，NASMX浓度高达20.36±1.98μg/g（根）和5.62±1.17μg/g（芽），SMX浓度高达15.97±2.53μg/g（根）和3.22±0.789微克/克（芽）。使用Orbitrap-HRMS进行非靶向筛选，鉴定出总共18种SMX中间转化产物，揭示了脱氨、羟基化、乙酰化、甲酰化和糖基化等途径。值得注意的是，NASMX 在大米中转化回 SMX，这是一个新颖的发现。转录组分析强调了细胞色素 P450 (CYP450)、乙酰转移酶 (ACE) 和糖基转移酶 (GT) 在这些生物转化途径中的参与。此外，暴露于SMX和NASMX会破坏水稻的TCA循环、氨基酸、亚油酸、核苷酸代谢和苯丙素生物合成途径，其中NASMX对代谢网络产生更强的影响。这些发现阐明了磺胺类药物的代谢和植物毒性机制，并有助于评估抗生素污染中的食品安全和人类暴露风险。