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Oral Microcystin-LR Does Not Cause Hepatotoxicity in Pigs: Is the Risk of Microcystin-LR Overestimated?
Exposure and Health ( IF 6.7 ) Pub Date : 2019-12-02 , DOI: 10.1007/s12403-019-00336-6
Richard D. Welten , Julie P. Meneely , Olivier P. Chevallier , Vít Kosek , Brett Greer , Jana Hajšlová , Christopher T. Elliott

The global increase of toxin-producing cyanobacteria poses a serious risk to humans. Many investigations have shown that the cyanotoxin microcystin-LR induces hepatotoxicity in rodents. However, many of these studies applied the toxin intraperitoneally or used high oral concentrations, leading to an unrealistically high bioavailability of the toxin. Such approaches have put into question how these results translate to human exposure scenarios. Epidemiology studies have linked microcystin-LR with hepatotoxicity and liver cancer in humans, though by design these investigations cannot provide direct evidence. The present work investigated the effect of microcystin-LR exposure on pigs closely mimicking real-life human conditions. In two animal experiments, pigs were administered microcystin-LR daily by oral gavage for 35 days. Metabolomic and lipidomic tools were used to analyse blood and liver samples. In addition, blood biochemistry parameters indicative of liver function and health were studied to further investigate the potential hepatotoxic effects of microcystin-LR. Results indicated that the metabolomic and lipidomic analyses did not show a gross treatment effect in blood and liver. Furthermore, no significant alterations were found in the tested blood biochemistry parameters. No evidence of hepatotoxicity was found. These results shed more light onto the effects (or lack of effects) of low-dose oral microcystin-LR exposure. The data suggests that the risk of oral microcystin-LR exposure may be overestimated.



中文翻译:

口服微囊藻毒素-LR不会对猪造成肝毒性:微囊藻毒素-LR的风险被高估了吗?

产生毒素的蓝细菌的全球增加对人类构成了严重的风险。许多研究表明,氰毒素微囊藻毒素-LR在啮齿动物中诱导肝毒性。但是,这些研究中有许多是通过腹膜内施用毒素或口服浓度较高的毒素,导致毒素的生物利用度异常高。这些方法使人们怀疑这些结果如何转化为人类暴露的情况。流行病学研究已将微囊藻毒素-LR与人类的肝毒性和肝癌相关​​联,尽管通过设计这些研究无法提供直接的证据。本研究调查了微囊藻毒素-LR暴露对模拟现实生活条件的猪的影响。在两个动物实验中,每天通过管饲法给猪施用微囊藻毒素-LR,持续35天。代谢组学和脂质组学工具用于分析血液和肝脏样本。此外,研究了指示肝功能和健康的血液生化参数,以进一步研究微囊藻毒素-LR的潜在肝毒性作用。结果表明,代谢组学和脂质组学分析未显示对血液和肝脏有明显的治疗作用。此外,在测试的血液生化参数中未发现明显变化。没有发现肝毒性的证据。这些结果为低剂量口服微囊藻毒素-LR暴露的影响(或没有影响)提供了更多线索。数据表明,口服微囊藻毒素-LR暴露的风险可能被高估了。研究了指示肝功能和健康的血液生化参数,以进一步研究微囊藻毒素-LR的潜在肝毒性作用。结果表明,代谢组学和脂质组学分析未显示对血液和肝脏有明显的治疗作用。此外,在测试的血液生化参数中未发现明显变化。没有发现肝毒性的证据。这些结果为低剂量口服微囊藻毒素-LR暴露的影响(或没有影响)提供了更多线索。数据表明,口服微囊藻毒素-LR暴露的风险可能被高估了。研究了指示肝功能和健康的血液生化参数,以进一步研究微囊藻毒素-LR的潜在肝毒性作用。结果表明,代谢组学和脂质组学分析未显示对血液和肝脏有明显的治疗作用。此外,在测试的血液生化参数中未发现明显变化。没有发现肝毒性的证据。这些结果为低剂量口服微囊藻毒素-LR暴露的影响(或没有影响)提供了更多线索。数据表明,口服微囊藻毒素-LR暴露的风险可能被高估了。在测试的血液生化参数中未发现明显变化。没有发现肝毒性的证据。这些结果为低剂量口服微囊藻毒素-LR暴露的影响(或没有影响)提供了更多线索。数据表明,口服微囊藻毒素-LR暴露的风险可能被高估了。在测试的血液生化参数中未发现明显变化。没有发现肝毒性的证据。这些结果为低剂量口服微囊藻毒素-LR暴露的影响(或没有影响)提供了更多线索。数据表明,口服微囊藻毒素-LR暴露的风险可能被高估了。

更新日期:2019-12-02
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