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Cellular injury leading to oxidative stress in acute poisoning with potassium permanganate/oxalic acid, paraquat, and glyphosate surfactant herbicide
Environmental Toxicology and Pharmacology ( IF 4.2 ) Pub Date : 2020-10-05 , DOI: 10.1016/j.etap.2020.103510
Thilini Madushanka Wijerathna 1 , Fahim Mohamed 2 , Indika Bandara Gawarammana 3 , Klintean Wunnapuk 4 , Dhammika Menike Dissanayake 5 , Fathima Shihana 6 , Nicholas Allan Buckley 6
Affiliation  

Previous studies on human acute kidney injury (AKI) following poisoning with potassium permanganate/oxalic acid (KMnO4/H2C2O4), paraquat, and glyphosate surfactant herbicide (GPSH) have shown rapid and large increases in serum creatinine (sCr) that cannot be entirely explained by direct nephrotoxicity. One plausible mechanism for a rapid increase in sCr is oxidative stress. Thus, we aimed to explore biomarkers of oxidative stress, cellular injury, and their relationship with sCr, after acute KMnO4/H2C2O4, paraquat, and GPSH poisonings. Serum biomarkers [sCr, creatine (sCn), cystatin C (sCysC)] and urinary biomarkers [cytochrome C (CytoC), 8-isoprostane (8-IsoPs)] were evaluated in 105 patients [H2C2O4/KMnO4 (N = 57), paraquat, (N = 21), GPSH (N = 27)] recruited to a multicenter cohort study. We used area under the receiver operating characteristics curve (AUC-ROC) to quantify the extent of prediction of moderate to severe AKI (acute kidney injury network stage 2/3 (AKIN2/3)). Patients with AKIN2/3 showed increased levels of CytoC. Early high CytoC predicted AKIN2/3 in poisoning with KMnO4/H2C2O4 (AUC-ROC4−8h: 0.81), paraquat (AUC-ROC4−8h: 1.00), and GPSH (AUC-ROC4−8h: 0.91). 8-Isoprostane levels were not significantly elevated. Reduced sCn and increased sCr/sCn ratios were observed for 48 h post KMnO4/H2C2O4 ingestion. Paraquat exhibited a similar pattern (N = 11), however only 3 were included in our study. Increased CytoC suggests there is mitochondrial injury coupled with energy depletion. The increased sCr within 24 h could be due to increased conversion of cellular creatine to creatinine during the process of adenosine triphosphate (ATP) generation and then efflux from cells. Later increases of sCr are more likely to represent a true decrease in kidney function.



中文翻译:


高锰酸钾/草酸、百草枯和草甘膦表面活性剂除草剂急性中毒时细胞损伤导致氧化应激



先前对高锰酸钾/草酸(KMnO 4 /H 2 C 2 O 4 )、百草枯和草甘膦表面活性剂除草剂(GPSH)中毒后人类急性肾损伤(AKI)的研究表明,血清肌酐(sCr)迅速大幅升高)不能完全用直接肾毒性来解释。 sCr 快速增加的一种可能机制是氧化应激。因此,我们的目的是探讨急性 KMnO 4 /H 2 C 2 O 4 、百草枯和 GPSH 中毒后氧化应激、细胞损伤的生物标志物及其与 sCr 的关系。对 105 名患者 [H 2 C 2 O 4 /KMnO 4 (N = 57)、百草枯、(N = 21)、GPSH (N = 27)] 被招募参加多中心队列研究。我们使用受试者工作特征曲线下面积 (AUC-ROC) 来量化中度至重度 AKI(急性肾损伤网络 2/3 期 (AKIN2/3))的预测程度。 AKIN2/3 患者的 CytoC 水平升高。早期高 CytoC 预测 KMnO 4 /H 2 C 2 O 4 (AUC-ROC 4−8h : 0.81)、百草枯 (AUC-ROC 4−8h : 1.00) 和 GPSH (AUC-ROC 4− 4−)中毒时出现 AKIN2/3 8 小时:0.91)。 8-异前列烷水平没有显着升高。 KMnO 4 /H 2 C 2 O 4摄入后48小时观察到sCn降低和sCr/sCn比率增加。 百草枯也表现出类似的模式(N = 11),但我们的研究中只纳入了 3 种。 CytoC 增加表明存在线粒体损伤并伴有能量消耗。 24小时内sCr增加可能是由于三磷酸腺苷(ATP)生成然后从细胞流出的过程中细胞肌酸转化为肌酐增加所致。随后 sCr 的增加更有可能代表肾功能的真正下降。

更新日期:2020-10-11
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