Procalcitonin Impairs Liver Cell Viability and Function In Vitro: A Potential New Mechanism of Liver Dysfunction and Failure during Sepsis?
Procalcitonin Impairs Liver Cell Viability and Function In Vitro: A Potential New Mechanism of Liver Dysfunction and Failure during Sepsis?
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DOI：
10.1155/2017/6130725
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发表时间：
2017
影响因子：
--
通讯作者：
Wagner NM
中科院分区：
文献类型：
--
作者：
Sauer M;Doß S;Ehler J;Mencke T;Wagner NM
目的.肝功能不全和肝衰竭是脓毒症的严重并发症，导致预后不良和死亡率增加。脓毒症时肝细胞功能障碍和坏死的病理机制还不完全清楚。在这里，我们研究了降钙素原，脓毒症的生物标志物，是否调节肝细胞功能和活力。材料和方法。采用先前表征和专利的生物传感器系统评价体外肝细胞毒性，将人肝细胞癌细胞（HepG 2/C3 A）暴露于0.01-50 ng/mL降钙素原2 × 72 h，并评价增殖、坏死、代谢活性、细胞完整性、微量白蛋白合成和解毒能力。对乙酰氨基酚作为阳性对照。为了进一步标准化，在采用L929成纤维细胞的细胞毒理学试验组中证实降钙素原的作用。使用ANOVA/Tukey检验分析数据。结果在低至0.25 ng/mL的浓度下，降钙素原诱导HepG 2/C3 A坏死（P < 0.05），并降低代谢活性、细胞完整性、合成和解毒能力（均P < 0.001）。使用L929成纤维细胞获得了相当的效果。结论我们提供了降钙素原直接损害人肝细胞功能和活力的证据，并在体外产生一般细胞毒性。因此，降钙素原的治疗靶向可能显示出一种新的方法，以减少脓毒症期间肝功能障碍和衰竭的发生率，并降低脓毒症患者的发病率和死亡率。
Purpose. Liver dysfunction and failure are severe complications of sepsis and result in poor outcome and increased mortality. The underlying pathologic mechanisms of hepatocyte dysfunction and necrosis during sepsis are only incompletely understood. Here, we investigated whether procalcitonin, a biomarker of sepsis, modulates liver cell function and viability. Materials and Methods. Employing a previously characterized and patented biosensor system evaluating hepatocyte toxicity in vitro, human hepatocellular carcinoma cells (HepG2/C3A) were exposed to 0.01–50 ng/mL procalcitonin for 2 × 72 h and evaluated for proliferation, necrosis, metabolic activity, cellular integrity, microalbumin synthesis, and detoxification capacity. Acetaminophen served as positive control. For further standardization, procalcitonin effects were confirmed in a cellular toxicology assay panel employing L929 fibroblasts. Data were analyzed using ANOVA/Tukey's test. Results. Already at concentrations as low as 0.25 ng/mL, procalcitonin induced HepG2/C3A necrosis (P < 0.05) and reduced metabolic activity, cellular integrity, synthesis, and detoxification capacity (all P < 0.001). Comparable effects were obtained employing L929 fibroblasts. Conclusion. We provide evidence for procalcitonin to directly impair function and viability of human hepatocytes and exert general cytotoxicity in vitro. Therapeutical targeting of procalcitonin could thus display a novel approach to reduce incidence of liver dysfunction and failure during sepsis and lower morbidity and mortality of septic patients.