Orlistat (ORL) has been employed as an anti-obesity pharmaceutical for several decades. Given its low absorption rate, the majority of administered ORL is excreted into the environment with feces. It is crucial to collect scientific information regarding the possible ecological risks associated with ORL. Here, the effects of ORL on Daphnia magna were evaluated using a 21-day chronic test at concentrations of 1, 10, 100, and 1000 μg/L. We found the inhibition of feeding and swimming activities in the 100 and 1000 μg/L ORL exposed D. magna, respectively. Their digestive enzyme activities and metabolites were reduced even at 1 μg/L ORL exposure. It is noteworthy that exposure to 100 μg/L ORL induced a decrease in the reproductive capacity of D. magna, although no discernible genotoxicity was observed. To identify the toxicological mechanisms of ORL, a metabolic analysis was conducted on D. magna exposed to 1000 μg/L ORL. A comprehensive reduction in carbohydrates, lipids, and amino acids was observed, which resulted in a blockage of metabolic flux towards the TCA cycle, as evidenced by mitochondrial dysfunction. These findings substantiate the detrimental impact of ORL on D. magna and provide insights into the underlying molecular mechanisms from a metabolic perspective.

中文翻译：

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奥利司他破坏大型水蚤能量稳态和繁殖的有害影响和机制


几十年来，奥利司他 （ORL） 一直被用作抗肥胖药物。鉴于其低吸收率，大多数给药的 ORL 随粪便排泄到环境中。收集有关与 ORL 相关的可能生态风险的科学信息至关重要。在这里，使用浓度为 1、10、100 和 1000 μg/L 的 21 天慢性试验评估 ORL 对大型溞的影响。我们发现 100 μg/L ORL 分别暴露于大型石楠中抑制摄食和游泳活动。即使在 1 μg/L ORL 暴露时，它们的消化酶活性和代谢物也降低。值得注意的是，暴露于 100 μg/L ORL 诱导了 D. magna 的繁殖能力下降，尽管没有观察到明显的遗传毒性。为了确定 ORL 的毒理学机制，对暴露于 1000 μg/L ORL 的大石栉进行了代谢分析。观察到碳水化合物、脂质和氨基酸的全面减少，这导致向 TCA 循环的代谢通量受阻，线粒体功能障碍证明了这一点。这些发现证实了 ORL 对 D. magna 的有害影响，并从代谢角度提供了对潜在分子机制的见解。