The significance of serum HMGB1 level in humans with acute paraquat poisoning

Abstract

High-mobility group box 1 (HMGB1) mediates acute lung injury in a mouse model of paraquat poisoning. However, published reports showing a clinically relevant association between HMGB1 and paraquat exposure are lacking. The objective of the present study was to investigate the potential role of serum HMGB1 level as a prognostic marker of mortality in patients with paraquat poisoning in a clinical setting. This retrospective observational cohort study included a convenience sample of 92 patients with acute paraquat poisoning admitted to the emergency room (ER) of The First Hospital of Jilin University between January 2014 and December 2016. Baseline serum HMGB1 levels and other laboratory parameters were measured on admission. Cumulative incidence of mortality during the first 30 days after admission was 50% (n = 46/92). Serum HMGB1 levels were higher in fatalities than survivors ( P = 0.015), 30-day mortality increased with increasing baseline serum HMGB1 level ( P < 0.001), and higher serum HMGB1 levels were associated with an increase in 30-day mortality on Kaplan-Meier analysis. Multivariate Cox regression analysis identified baseline serum HMGB1 levels, white blood cell count, and serum lactic acid levels as independent prognostic markers of 30-day mortality. These data suggest that serum HMGB1 levels measured on admission to the ER are an independent predictor of 30-day mortality in patients with acute paraquat poisoning.

Identification of Serum-Based Metabolic Feature and Characteristic Metabolites in Paraquat Intoxicated Mouse Models

“…Paraquat induces oxidative damage and cell death by generation of reactive oxygen species (ROS) including hydrogen peroxide, superoxide anion, and hydroxyl radicals (Fan et al, 2018;Chen et al, 2019a), and induction of cellular apoptosis (Kong et al, 2019). PQ toxicity is related to its capacity to capture electrons in cellular redox reactions and inhibit the reduction of NADP + to NADPH in the cytosolic fraction, which induce oxidative stress by the overproduction of superoxide anion (O 2− ) (Baltazar et al, 2014;Blanco-Ayala et al, 2014).…”

“…Gas chromatography-time-of-flight mass spectrometry (GC-TOF/MS) is one of the most widely used platforms in non-targeted metabolomics studies (Lenz and Wilson, 2007), which provides high chromatographic resolution, high mass measurement accuracy, and rapid spectrum acquisition (Ni et al, 2016). Given the poor prognosis of PQ intoxication, previous studies focused on mining potential prognosis biomarkers from patient samples by either metabolomics or other non-highthroughput approaches (Yeo et al, 2012;Wunnapuk et al, 2013;Wan et al, 2018;Chen et al, 2019a). Relatively few studies paid attention to the metabolic feature caused by PQ exposure to help us investigate the underlying mechanisms, which might contribute to develop new therapeutic targets and diagnosis biomarkers.…”

Prognostic value of liver and kidney function parameters and their correlation with the ratio of urine‐to‐plasma paraquat in patients with paraquat poisoning

“…However, notably, patients are still likely to face death even at low plasma paraquat concentrations 9 . More recently, some biochemical indicators have been reported to potentially guide the prognosis of paraquat poisoning, including pancreatic enzymes, high‐mobility group box 1 (HMGB1), serum creatinine, serum uric acid and others 13‐16 . Although these biochemical indicators can somehow reflect the damage degree of corresponding organs, the hysteresis phenomena and the fact that multiple organs were not taken into account have limited the reliability and prognostic values of these parameters.…”

Aspirin Eugenol Ester Attenuates Paraquat-Induced Hepatotoxicity by Inhibiting Oxidative Stress

“…et al, 2019;Shao et al, 2019). PQ is extremely toxic to humans (Xu et al, 2017;Chen F. et al, 2019). Studies have shown that when ingesting about 10 ml PQ, patients can die of multiple organ failure a few hours later (Feng et al, 2018).…”