Multi-generational effects of enrofloxacin on lifespan and reproduction of Caenorhabditis elegans with SKN-1-mediated antioxidant responses and lipid metabolism disturbances.
Multi-generational effects of enrofloxacin on lifespan and reproduction of Caenorhabditis elegans with SKN-1-mediated antioxidant responses and lipid metabolism disturbances.
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DOI：
10.1016/j.scitotenv.2021.150250
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发表时间：
2022-01
期刊：
影响因子：
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通讯作者：
Yungu Zheng;Zhenyang Yu;Jing Zhang
中科院分区：
文献类型：
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作者：
Yungu Zheng;Zhenyang Yu;Jing Zhang
抗生素是普遍存在的环境污染物，由于其伪持久性，它们可以引起多代人的影响。然而，其多代效应和潜在机制的研究仍然很少。目前，恩诺沙星（ENR）的影响进行了研究，在环境现实的水平上，连续暴露9代（从F1到F9）的秀丽隐杆线虫。关于生殖，ENR显示F1（对照的1.18倍）和F2（1.08）中有刺激作用，F3（0.70）中有抑制作用，F4（1.86）、F5（3.18）和F6（1.53）中有刺激作用，F7（0.73）和F8（0.69）中有抑制作用，F9（1.89）中再次有刺激作用。也就是说，ENR对繁殖产生了多代振荡效应。这种振荡对寿命的影响也比对生殖的影响小得多。在F_1、F_3、F_4和F_9中进行生化测定，这代表了世代间的振荡。结果显示更多的抗氧化剂（例如，超氧化物歧化酶和谷胱甘肽），轻度氧化应激（例如，活性氧物质）和较少的氧化损伤（即，蛋白质羰基）的生成依赖性刺激的基础。此外，ENR引起调节脂肪生成的酶的多代振荡（例如，脂肪酸合成酶和乙酰辅酶A羧化酶）和脂解（例如，酰基辅酶A合成酶），与对氧化应激和损伤的作用相似。对SKN-1及其活化的PMK-1和GSK-3的进一步分析表明，它们参与调节抗氧化解毒和脂质代谢。
Antibiotics are ubiquitous environmental pollutants and they can provoke multi-generational impacts due to their pseudo-persistence. However, their multi-generational effects and potential mechanisms remained poorly studied. Presently, effects of enrofloxacin (ENR) were studied on Caenorhabditis elegans with a continuous exposure over 9 generations (from F1 to F9) at an environmentally realistic level. Regarding reproduction, ENR showed stimulation in F1 (1.18-fold of the control) and F2 (1.08), inhibition in F3 (0.70), stimulation in F4 (1.86), F5 (3.18) and F6 (1.53), inhibition in F7 (0.73) and F8 (0.69) and stimulation again in F9 (1.89). That is to say, ENR provoked multi-generational oscillatory effects on the reproduction. Such oscillation was also observed in effects on lifespan with much less magnitudes than those on reproduction. Biochemical assays were performed in F1, F3, F4 and F9 which represented the oscillation over generations. Results showed more antioxidants (e.g., superoxide dismutase and glutathione), mild oxidative stress (e.g., reactive oxygen species) and less oxidative damage (i.e., protein carbonyl) underlying the generation-dependent stimulation. Moreover, ENR provoked multi-generational oscillation on the enzymes that regulate the lipogenesis (e.g., fatty acid synthase and acetyl-CoA carboxylase) and lipolysis (e.g., acyl-CoA synthetase), with similarities to the effects on the oxidative stress and damage. Further analysis on SKN-1 and its activating PMK-1 and GSK-3 demonstrated their involvement in regulating both antioxidant detoxification and lipid metabolism.