Lassoued Amal, Boufahja Fehmi, Plavan Gabriel, Ben Hamadi Naoufel, Ali Mohamed A M, Elfalleh Walid, Badraoui Riadh, Bendif Hamdi, Hedfi Amor
Coastal Ecology and Ecotoxicology Unit, Laboratory of Environment Biomonitoring, Faculty of Sciences of Bizerte, University of Carthage, Zarzouna 7021, Tunisia.
Biology Department, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia.
Toxics. 2025 Mar 31;13(4):264. doi: 10.3390/toxics13040264.
In the current research, we examined the effects of warfarin (W1 = 5 mg/L and W2 = 25 mg/L) and tinzaparin (T1 = 5 mg/L and T2 = 25 mg/L) on meiofauna using microcosms. These microcosms were intentionally contaminated with both anticoagulants for one month. The findings indicated that nematodes and amphipods demonstrated the greatest resistance to the two anticoagulants evaluated. Specifically, the number of amphipods increased after exposure to the treatment that included T2. Following the separate introduction of each drug, amphipods displayed a taxonomic restructuring, with a more significant impact observed from T2 and T2W1. Results were derived from multivariate analyses of a compilation of sensitive amphipod taxa in response to tinzaparin and warfarin. In contrast, different species were identified as positive indicators for tinzaparin. Ultimately, the similarity between the control amphipod replicates and those subjected to mixed anticoagulants (T1W1 and T2W2) suggests that warfarin may have reduced the toxicity of tinzaparin. Additionally, the computational study indicated that warfarin interacts with 4XNN and forms strong molecular interactions with several key residues, which contribute to the toxicokinetic characteristics observed in the empirical findings.
在当前研究中，我们使用微观生态系统研究了华法林（W1 = 5毫克/升和W2 = 25毫克/升）和替扎肝素（T1 = 5毫克/升和T2 = 25毫克/升）对小型底栖生物的影响。这些微观生态系统被故意用两种抗凝剂污染了一个月。研究结果表明，线虫和双足类动物对所评估的两种抗凝剂表现出最大的抗性。具体而言，双足类动物的数量在暴露于包含T2的处理后有所增加。在分别引入每种药物后，双足类动物显示出分类重组，其中T2和T2W1的影响更为显著。结果来自对敏感双足类分类群对替扎肝素和华法林反应的汇编进行的多变量分析。相比之下，不同的物种被确定为替扎肝素的阳性指标。最终，对照双足类重复样本与接受混合抗凝剂（T1W1和T2W2）处理的样本之间的相似性表明，华法林可能降低了替扎肝素的毒性。此外，计算研究表明，华法林与4XNN相互作用，并与几个关键残基形成强烈的分子相互作用，这有助于解释实验结果中观察到的毒代动力学特征。
