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.
Highlights
Paraquat is an organic compound containing the active ingredient 1,1′-dimethyl-4,4′-bipyridinium dichloride that is widely used as a herbicide
We reported that a signaling cascade involving high-mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), interleukin 23 (IL23), and IL17A mediated acute lung injury (ALI) in a mouse model of paraquat poisoning[7]
21 patients had diabetes mellitus, 29 patients had hypertension. 19 patients had renal failure, 22 patients had malignancy, 104 patients had inadequate follow up data, and >24 hours had passed since the oral intake of paraquat in 17 patients
Summary
Paraquat is an organic compound containing the active ingredient 1,1′-dimethyl-4,4′-bipyridinium dichloride that is widely used as a herbicide. Recent evidence suggests that the molecular mechanisms underlying paraquat toxicity include the release of damage-associated molecular patterns, including high-mobility group box 1 (HMGB1), a chromatin-binding protein that can be secreted by necrotic or inflammatory cells. We reported that a signaling cascade involving HMGB1, toll-like receptor 4 (TLR4), interleukin 23 (IL23), and IL17A mediated acute lung injury (ALI) in a mouse model of paraquat poisoning[7]. These findings suggest that targeting the HMGB1-TLR4-IL23-IL17A axis represents a potential therapeutic strategy for treating paraquat poisoning. 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
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