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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 4.3 ) Pub Date : 2020-10-05 , DOI: 10.1016/j.etap.2020.103510
Thilini Madushanka Wijerathna , Fahim Mohamed , Indika Bandara Gawarammana , Klintean Wunnapuk , Dhammika Menike Dissanayake , Fathima Shihana , Nicholas Allan Buckley

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引起的急性中毒导致的细胞氧化应激

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)中毒后的人类急性肾损伤(AKI)的研究表明,血清肌酐(sCr)迅速大量增加)不能完全由直接的肾毒性来解释。sCr快速增加的一种可能机制是氧化应激。因此,我们旨在探讨急性KMnO 4 / H 2 C 2 O 4后氧化应激,细胞损伤及其与sCr的关系的生物标志物。,百草枯和GPSH中毒。在105例患者中评估了血清生物标志物[sCr,肌酸(sCn),胱抑素C(sCysC)]和尿液生物标志物[细胞色素C(CytoC),8-异前列腺素(8-IsoPs)] [H 2 C 2 O 4 / KMnO 4(N = 57),百草枯(N = 21),GPSH(N = 27)]参加了一项多中心队列研究。我们使用接收器工作特征曲线(AUC-ROC)下的面积来量化中度至重度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。早期的高CytoC预测AKM2 / 3在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 4-8h:0.91)。8-异前列腺素水平没有显着升高。摄入KMnO 4 / H 2 C 2 O 4后48小时,观察到sCn降低和sCr / sCn比增加。百草枯表现出相似的模式(N = 11),但是我们的研究仅包括了3种。CytoC升高表明存在线粒体损伤并伴有能量消耗。24小时内sCr的增加可能是由于在三磷酸腺苷(ATP)生成过程中细胞肌酸向肌酸酐的转化增加,然后从细胞流出。以后sCr的增加更可能代表肾脏功能的真正降低。

更新日期:2020-10-11
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