Acute Paraquat Poisoning Research Articles

Diagnostic and therapeutic approach for acute paraquat intoxication.

Paraquat (PQ) has known negative human health effects, but continues to be commonly used worldwide as a herbicide. Our clinical data shows that the main prognostic factor is the time required to achieve a negative urine dithionite test. Patient survival is a 100% when the area affected by ground glass opacity is <20% of the total lung volume on high-resolution computed tomography imaging 7 days post-PQ ingestion. The incidence of acute kidney injury is approximately 50%. The average serum creatinine level reaches its peak around 5 days post-ingestion, and usually normalizes within 3 weeks. We obtain two connecting lines from the highest PQ level for the survivors and the lowest PQ level among the non-survivors at a given time. Patients with a PQ level between these two lines are considered treatable. The following treatment modalities are recommended to preserve kidney function: 1) extracorporeal elimination, 2) intravenous antioxidant administration, 3) diuresis with a fluid, and 4) cytotoxic drugs. In conclusion, this review provides a general overview on the diagnostic procedure and treatment modality of acute PQ intoxication, while focusing on our clinical experience.

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Introduction: In this study, we aim to investigate the changes of PERK-eIF2a-ATF4 signaling pathway in endoplasmic reticulum stress after acute paraquat (PQ) poisoning; and to clear Salubrinal (Sal) effects on PERK-eIF2a-ATF4 signaling pathway and lung injury caused by paraquat. Methods: 200 Wistar rats were chosen from Experimental Animal Center of Jilin University, weighted 250 +10g each, half male and half female.These rats were randomly divided into 4 groups, 50 rats in each group. Group A: control group, the rats were given gastric lavage with 1 ml of normal saline once only and 1ml of saline by intraperitoneal injection twice daily. Group B: poisoned-nontreated group: the rats were given gastric lavage with PQ solution of 40ml/kg once only and 1ml of saline by intraperitoneal injection twice daily. Group C:the rats were given Sal (0.5mg/kg) of 1ml and 1ml of saline once daily by intraperitoneal injection in the 1st,3rd,and 5th day after PQ poisoning. Group D: Sal (1.0mg/kg) treatment group, the rats were given Sal (1.0mg/kg) 1ml and 1ml saline once daily by intraperitoneal injection in the 1st,3rd,and 5th day after PQ poisoning. Then we observed the general state of rats, and in the 7th day after poisoning, the lungs were taken and the lung tissue morphology were obererved by HE staining. The expression of PERK, P-elF2a, ATF4 were detected by immunohistochemistry, and the expression of GRP78, PDI, PERK, P-elF2a, ATF4 and CHOP protein were detected by western blotting in lung tissue.Then we did statistical analysis. Results: In the 7th day of acute PQ poisoning, HE staining of lung tissue exposed that there was a lot of inflammatory exudation in group B; the expression of GRP78, PDI, PERK, P-elF2a, ATF4 and CHOP protein were higher than that of the control group, with the difference statistically significant (P <0.05). There was basal expression of GRP78, PDI, PERK, P-elF2a, ATF4 and CHOP in the control group. The inflammatory response in Salubrinal treatment group was more serious than that of the exposure group, the expression of GRP78, PDI, PERK, P-elF2a, ATF4 and CHOP protein was increased, with the difference statistically significant (P <0.05). The degree of inflammation and protein expression in Sal (0.5mg/kg) treatment group was between Sal (1.0mg/kg) treatment group and the exposure group, with the difference statistically significant (P <0.05). Mortality: The mortality of group B,group C and group D were 54.0%, 70.0%, 88.0%; and the mortality of Sal (1.0mg/kg) treatment group was the highest,with the difference statistically significant (P <0.05). Conclusions: Acute PQ poisoning can enhance ERS, PERK-eIF2a-ATF4 signaling pathway and cause lung injury; Salubrinal can strengthen ERS, increase PERK-eIF2a-ATF4 signal transduction pathway and aggravate acute lung injury caused by PQ poisoning.

Arterial lactate as a predictor of mortality in emergency department patients with acute paraquat poisoning

Objective To study the prognostic value of initial arterial lactate level and to explore the relationship between early arterial lactate and the outcome of patients with acute paraquat poisoning by analyzing the clinical data of 235 cases.Methods A total of 235 patients with acute paraquat poisoning were admitted to the Emergency Intensive Care Unit (EICU) from January 2009 to June 2012.Demographics,clinical and laboratory findings were compared between the survivors and non-survivors.Receiver operating characteristic (ROC) curves were used to identify the optimal cut-off points for initial arterial lactate level.Results Totally 235 patients with average age of (33.6 ± 11.5) years old (ranging from 18 to 74),89 male and 146 female.The median estimated amount of 20％ paraquat ingested was 55 mL,(ranging from 10 to 280,IQR:27 mL,77 mL),the median length of time between paraquat ingestion and the arrival at the emergency department was 4.5 h (ranging from 0.5 to 10.5,IQR:2.3 h,6.8 h).The overall mortality rate was 74.0％ (174/235) during a 28 days follow-up period,only 61 of 235 patients survived.The initial arterial lactate level was higher in non-survivors than that in survivors (2.79 ± 0.76) mmol/L vs.(1.62 ± 0.48) mmol/L,P =0.028).Correlation analyses showed that the initial arterial lactate level was associated with increased risk of 28-day mortality (r =0.26,P =0.004),and as the initial lactate increased,the survival time of non-survivors shortened (F =3.246,P =0.037).Using the ROC curve analysis,the initial arterial lactate level had an area of 0.799 (95％ CI:0.745-0.866) and the cut-off point of concentration was 2.57 mmol/L for prediction of prognosis in patients with acute paraquat poisoning (sensitivity 85.2％,specificity 79.6％,the best Youden index was 0.648).The initial arterial lactate level was higher in patients died from circulatory failure rather than from respiratory failure (5.22 ± 1.46) mmol/L vs.(1.87 ± 0.62) mmol/L,P =0.042.And the survival time of patients died from circulatory failure was shorter than that from respiratory failure (4.1 ± 1.3) d vs.(11.6 ± 3.2)d,P =0.023.With the ROC curve analysis,the initial arterial lactate level had an area of 0.882 (95％ CI:0.805-0.941) and the cut-off point of concentration was 3.65 mmol/L for prediction of prognosis of patients died from circulatory failure (sensitivity 87.6％,specificity 82.5％,the best Youden index was 0.701).Conclusions The initial arterial lactate level may be one of early indicators of prognosis in patients with acute paraquat poisoning and it had high potential in predicting the outcome of patients died from circulatory failure. Key words: Lactate; Paraquat; Poisoning; Prognosis

The effect of lipoic acid on SP-A and SP-B during acute paraquat poisoning

Objective To observe the changes in concentrations of pulmonary surfactant SP-A/B in lung tissue during acute lung injury (ALI) /acute respiratory distress syndrome (ARDS) induced by acute paraquat poisoning (PQP) after the treatment with metabolic antioxidant,lipoic acid,and to explore the potential involvement of TNF-α in ALI/ARDS as well as to discuss the assumed protective mechanisms of lipoic acid against acute lung injury.Methods Sixty-six male Sprage-Dawley rats were randomly (random number) divided into 3 groups,namely control group (NS,n =6),paraquat poisoning group (PQ,n =30),paraquat + lipoic acid treatment group (LA,n =30).Then both group PQ and group LA were further divided separately into five subgroups,namely 3,6,12,24 and 48 h subgroups (n =6 in each subgroup).After rats sacrificed,the lung tissues were selected,and after HE staining,histological changes were observed under light microscope.Histopathological changes were inflammation and fibrosis in models successfully established.The lung tissues were also taken for tests of SOD and MDA levels.Specimens of whole blood 0.8 mL without anticoagulant were taken from tail vein of rats for determining the TNF-α level.The expressions of SP-A mRNA and SP-B mRNA were measured with RT-PCR from total RNA of the lung tissue.Results ① HE staining showed that the histopathological changes were milder in LA group than that in PQ group.② There were significant differences in MDA and SOD levels between different intervals both in intergroups and intragroup except the groups of 3 hours (P ＜ 0.01).③ Likewise,the significant differences in the levels of TNF-α were also present between three groups and between different intervals (P＜0.01).④ The significant differences in SP-A mRNA and SP-B mRNA amplification ratio existed between three groups at the same interval (P ＜ 0.01),but those differences between different intervals in group PQ were of statistical significance (P ＜ 0.05).And those differences between diffirent intervals in group LA were statistically significant (P ＜0.01).Conclusions Lipoic acid in acute paraquat poisoning could lessen lung tissue damage,which might be directly dominated by the levels of tumor necrosis factor,and in turn indirectly affect the content of pulmonary surfactant,thereby reducing pulmonary edema and improving lung compliance,then protecting the lung tissues. Key words: Lipoic acid ; Paraquat; Acute lung injury ; Surfactant protein ; Tumor necrosis factor-α; Oxygen free radical; Superoxide dimutase; Malonaldehyde

Application of focused settlement mode in the care of acute paraquat poisoning patients

Objective To explore the effects of focused settlement mode applied in caring the acute paraquat poisoning patients.Methods 106 hospitalized patients with acute paraquat poisoning were randomly divided into the control group and the experimental group.All patients in the control group were performed conventional nursing instruction and the experimental group was nursed with focused settlement mode on the basis of conventional nursing instruction.The efficacy of nursing was evaluated when they were discharged from hospital.Results The self-care skills and knowledge,consciously following the medical behavior,satisfaction degree with clinical service of the experimental group were significandy better than the control group,while the hospitalization days were shorter than the control group.Conclusions Focused settlement mode can improve the effect of nursing care for patients with acute paraquat poisoning. Key words: Acute paraquat poisoning; Focused settlement mode; Nursing

Effects of sivelestat treatment on acute lung injury in paraquat-intoxicated rats

Lung injury is the main cause of death in acute paraquat (PQ) intoxication. Sivelestat (SV), a neutrophil elastase inhibitor, is effective in reducing inflammation in acute lung injury. The aim of this study was to examine the effect of SV on acute lung injury in PQ-intoxicated rats. Seven-week-old male Sprague-Dawley rats were randomly assigned to four groups: (1) control group (group N; n = 5); (2) PQ + normal saline (group P; n = 6); (3) normal saline + SV (group S; n = 6) and (4) PQ + SV (group PS; n = 6). SV treatment (intraperitoneally [i.p.], 20 mg/kg) was performed 30 minutes after PQ injection (i.p., 100 mg/kg), and injections were continued every hour for a total of five doses. One hour after the last treatment, blood samples were obtained for analysis of interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α). Lung sections were stained with hematoxylin--eosin for light microscopic analysis. Neutrophil infiltration score of group PS was significantly lower than that of group P (p < 0.05). But, other scores and total score had no significant differences. IL-6 of group PS did not differ, compared to group P. In addition, there were no differences among the four groups. TNF-α of group PS was reduced, in comparison to the level of group P. SV attenuated neutrophil infiltration in PQ-induced acute lung injury in rats. In addition, systemic inflammation was partially suppressed with SV treatment, suppressing TNF-α production. These results suggest that SV reduces paraquat-induced lung injury, at least partially, by inhibiting neutrophil infiltration and TNF-α secretion.

Treatment of acute paraquat intoxication using recommended megadose of vitamin C: A reappraisal

Megadose of vitamin C (MVC) has been proposed for an emergent treatment of acute paraquat (PQ) poisoning. However, the safety issue of this treatment protocol has not been evaluated. Here, we present the first evidence that vitamin C can promote aggravated production of hydroxyl radical (OH•) via interacting with preexisting PQ+•/H2O2 system in a nonmetal-catalyzed manner. This enhanced oxidative stress would therefore expect to cause more deleterious effect during acute PQ intoxication. To lend support to this possibility, we set out to attest the effects of MVC on a simulated, PQ-intoxicated, Madin–Darby canine kidney (MDCK) cell model. First, PQ alone could trigger oxidative–nitrosative stress (ONS) through robust generation of reactive oxygen species and nitric oxide (NO) that could induce apoptotic killing via promoting effective release of mitochondrial cytochrome c, an apoptogenic factor. The percentage of apoptosis for MDCK cells treated with 1.0 mM PQ for 24 h was 16.3 ± 13.0%. However, when MDCK cells were treated with a combination of PQ (1.0 mM) and MVC (20 mM) for 24 h, the severity of apoptotic killing was further exacerbated as reflected by a nearly 7-fold increase in the release of mitochondrial cytochrome c and the percentage of apoptotic cell population rose sharply to 90.7 ± 5.1%. These data indicate that MVC apparently exacerbates further killing rather than cytoprotection on this simulated, PQ-intoxicated MDCK cell model and suggest that the treatment of PQ poisoning using MVC protocol should be cautious.

Value of arterial lactic acid and buffer excess in predicting the prognosis of patients with paraquat poisoning

To investigate the early prognostic values of arterial lactate and base excess (BE) in patients with paraquat poisoning. Seventy-five patients with paraquat poisoning were divided into sudden death group (n = 10) who died within 24 h after admission, recent death group (n = 31) who died more than 24 h after admission, and survival group (n = 34). Arterial lactate and BE were measured on admission and at 24 h after admission. The prognostic values of arterial lactate and BE were analyzed. The arterial lactate measured on admission was significantly higher in the sudden death group than in the recent death group and survival group (P < 0.01), but there was no significant difference in arterial lactate between the recent death group and survival group (P = 0.309). The BE measured on admission was significantly lower in the sudden death group than in the recent death group and survival group, and it was significantly lower in the recent death group than in the survival group (P < 0.01 or P < 0.05). At 24 h after admission, the recent death group had a significantly higher arterial lactate (P < 0.01) and a significantly lower BE (P < 0.01), as compared with the survival group. The logistic regression analysis showed that the two indices were significantly associated with prognosis (P < 0.01). On admission, the areas under the receiver operating characteristic (ROC) curve (AUCs) of arterial lactate and BE for predicting death were 0.692 and 0.787, respectively, and the cut-off values were 3.25 mmol/L and -1.75 mmol/L, respectively; the AUCs of arterial lactate and BE for predicting sudden death were 0.995 and 1, respectively, and the cut-off values were 7.1 mmol/L and -12.8 mmol/L, respectively. At 24 h after admission, the AUCs of arterial lactate and BE for predicting death were 0.743 and 0.822, respectively, and the cut-off values were 2.15 mmol/L and -5.55 mmol/L, respectively. Arterial lactate and BE have certain values in predicting the death, especially the sudden death, in patients with acute paraquat poisoning.

Prognostic significance of serum lactic acid in evaluation of acute paraquat poisoning patients

To discuss the role of serum lactic acid (Lac) level in evaluation of prognosis of acute paraquat poisoning (APP) patients. Clinical data from 168 APP patients were retrospectively analyzed. The serum Lac level and the plasma paraquat concentrations at admission were collected, and the severity index of paraquat poisoning (SIPP) were calculated. The patients were divided into <10, 10-50, ≥50 h×mg×L(-1) groups on the basis of SIPP. The correlation between Lac and SIPP was analyzed, as well as the role in evaluating prognosis. The higher the SIPP level, the higher the Lac level [2.00 (1.50, 2.83) mmol/L, 3.10 (1.73, 5.15) mmol/L, 8.95 (5.90, 13.10) mmol/L, all P<0.05]; Lac was correlated positively with SIPP (r=0.569, P<0.05). The higher the SIPP, the higher the mortality of patients [17.4% (15/86), 61.5% (24/39), 97.7% (42/43), all P<0.05]. The survival days of SIPP≥50 h×mg×L(-1) group was shorter than that in SIPP<10 h×mg×L(-1) group and 10-50 h×mg×L(-1) group [2.0 (1.0, 3.0) days vs. 9.0 (4.0, 11.0) days and 5.0 (3.0, 10.0) days, both P<0.05]. A negative correlation was found between Lac, SIPP and survival days in non-survivors (r1=-0.778, r2=-0.621, both P<0.05). Logistic regression analyses showed either Lac or SIPP was of prognostic significance [odds ratio (OR) of Lac: 1.758, 95% confidence interval (95%CI) 1.278-2.417;OR of SIPP: 1.063,95%CI 1.025-1.103, both P=0.001]. The area under the receiver operating characteristic curve (ROC curve) of Lac, SIPP and prognosis were 0.885 and 0.897 respectively (both P<0.05), Lac≥3.35 mmol/L was the best cut-off value, the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and accuracy for predicting the death were 74.07%, 90.80%, 88.24%, 79.00%, 8.056, 0.286 and 82.74% respectively; the evaluation value was closed to SIPP≥13.83 h×mg×L(-1) (77.78%, 91.95%, 90.00%, 81.63%, 9.677, 0.242 and 85.12%, respectively). The change in serum Lac level has evaluation value of the severity and prognosis for APP patients, and Lac≥3.35 mmol/L can be made as a simple and easy indicator for prognosis of APP patients.

Amelioration of Paraquat-Induced Pulmonary Injury by Mesenchymal Stem Cells

Acute paraquat (PQ) poisoning induces redox cycle and leads to fatal injury of lung. Clinical management is supportive in nature due to lack of effective antidote, and the mortality is very high. Mesenchymal stem cells (MSCs) process the properties of immunomodulation, anti-inflammatory, and antifibrotic effects and oxidative stress resistance. MSC transplantation may theoretically serve as an antidote in PQ intoxication. In this study, we examined the potential therapeutic effects of MSCs in PQ-induced lung injury. The degree of PQ toxicity in the rat type II pneumocyte cell line, L2, and MSCs was evaluated by examining cell viability, ultrastructural changes, and gene expression. L2 cells treated with 0.5 mM PQ were cocultured in the absence or presence of MSCs. For the in vivo study, adult male SD rats were administered an intraperitoneal injection of PQ (24 mg/kg body weight) and were divided into three groups: group I, control; group II, cyclophosphamide and methylprednisolone; group III, MSC transplantation 6 h after PQ exposure. MSCs were relatively resistant to PQ toxicity. Coculture with MSCs significantly inhibited PQ accumulation in L2 cells and upregulated the expression of antioxidative heme oxygenase 1 and metallothionein 1a genes, reversed epithelial-to-mesenchymal transition, and increased the viability of PQ-exposed L2 cells. Treatment with MSCs resulted in a significant reduction in severity of liver and renal function deterioration, alleviated lung injury, and prolonged the life span of rats. Altogether, our results suggest that MSCs possess antidote-like effect through multifactorial protection mechanism. The results of this preclinical study demonstrate that transplantation of MSCs may be a promising therapy and should be further validated clinically.

Renal biomarkers predict nephrotoxicity after paraquat

Paraquat is a widely used herbicide which has been involved in many accidental and intentional deaths. Nephrotoxicity is common in severe acute paraquat poisoning. We examined seven renal injury biomarkers, including cystatin-C, kidney injury molecule-1, β2-microglobulin, clusterin, albumin, neutrophil gelatinase-associated lipocalin and osteopontin, to develop a non-invasive method to detect early renal damage and dysfunction and to compare with the conventional endogenous marker creatinine. Male Wistar rats were dosed orally with four different doses of paraquat, and the biomarker patterns in urine and plasma were investigated at 8, 24 and 48h after paraquat exposure. By Receiver Operating Characteristic analysis, urinary kidney injury molecule-1 was the best marker at predicting histological changes, with areas under the Receiver Operating Characteristic curve of 0.81 and 0.98 at 8 and 24h (best cut-off value>0.000326μg/ml), respectively. Urinary kidney injury molecule-1, urinary albumin and urinary Cystatin-C elevations correlated with the degree of renal damage and injury development. Further study is required to compare biomarkers changes in rats with those seen in human poisoning.

Predictive value of 3 methods in severity evaluation and prognosis of acute paraquat poisoning

To evaluate the predictive value of 3 methods, namely plasma paraquat concentration, severity index of paraquat poisoning (SIPP), and acute physiology and chronic health evaluation (APACHE II) in severity evaluation and prognosis of acute paraquat poisoning. A total of 73 acute paraquat poisoning patients with oral administration were collected. Paraquat concentration in the plasma and other parameters on admission for SIPP and APACHE II were taken from medical records. According to the clinical outcome in the hospital or 7 days after the discharge, discrimination and calibration test were performed to evaluate the prognosis of the 3 methods. Discrimination of the 3 methods was greater than 0.8, and the area under the receiver operator curve for SIPP (0.938) was greater than paraquat concentration in the plasma (0.857) and APACHE II (0.801) with statistical significance (z=2.429, 2.021; P=0.015, 0.043). Difference in plasma paraquat concentration (0.857) and APACHE II (0.801) had no statistical significance (z=0.755, P=0.450). Hosmer-Lemeshow good fit test suggested better calibration value with statistical significance for the 3 methods (P>0.05). The 3 methods are valid in the severity evaluation and prognosis of acute paraquat poisoning. SIPP is the most preferred method, followed by paraquat concentration on admission. When there is no facility to measure paraqut concentration, APACHE II can be used as a reference for the death risk in acute paraquat poisoning.

Prognostic value of initial arterial lactate level and lactate metabolic clearance rate in patients with acute paraquat poisoning

ObjectiveThe aim of this study is to evaluate the prognostic value of initial arterial lactate level and 12-hour lactate metabolic clearance rate (MCR) in patients with acute paraquat poisoning. MethodsA total of 204 patients with acute paraquat poisoning were admitted to the Emergency Intensive Care Unit at The First Affiliated Hospital of China Medical University from January 2009 to December 2011. ResultsThe overall mortality rate was 72.5% (148/204) during a 28-day follow-up period; only 56 of 204 patients with acute paraquat poisoning survived. The initial arterial lactate level was higher in nonsurvivors than in survivors (P = .026). The 12-hour lactate MCR was lower in nonsurvivors than in survivors (P = .040). The initial arterial lactate level (P = .004) and 12-hour lactate MCR (P < .001) were associated with increased risk in 28-day mortality. In the receiver operating characteristic curve analysis, the initial arterial lactate level had an area of 0.749 (95% confidence interval, 0.714-0.856) and a cutoff concentration at 2.5 mmol/L (sensitivity = 84.6%, specificity = 79.2%, Youden index = 0.64). The 12-hour lactate MCR had an area of 0.871 (95% confidence interval, 0.807-0.935), and the cutoff was at 13.5% (sensitivity = 87.1%, specificity = 84.3%, Youden index = 0.71). ConclusionsThe initial arterial lactate level and 12-hour lactate MCR had good predictive powers in evaluating the prognosis of patients with acute paraquat poisoning, which may prove to be simpler and more practical tools in assessing the severity of paraquat poisoning.

Analysis of clinic efficacy on early repeated hemoperfusion in patients with acute paraquat poisoning

Objective To explore the clinic efficacy on early repeated hemoperfusion in patients with acute paraquat (PQ) poisoning by analyzing the clinical data of 168 patients.Methods A total of 168 patients with acute paraquat poisoning,admitted to our emergency intensive care unit (EICU) from January 2008 to February 2011 were retrospectively analyzed.The PQ poisoning patients were divided into HP group (n =81,group A) and non-HP group (n =87,group B).The early repeated HP was carried out for at least 2 times within 24 hours after poisoning.The chi-square test and t test were used to detect the difference in outcome between groups.Results There were 52 patients (64.2％) in group A died and 68 fatalities (78.2％) in group B (x2 =4.01,P =0.042).The first HP was carried out in patients of group A within (3.6 ± 3.3) h after poisoning,and the patients in the group A received HP for (2.9 ± 1.4) times.On the second day after poisoning,sequential organ failure assessment (SOFA) scores of 168 patients were higher than those at admission (P ＜ 0.05).SOFA scores of patients in the group A were higher than that in the group B on the third day and on the forth day (P ＜ 0.05).In the group B,alanine aminotransferase (ALT)＞ 80 U/L and total bilirubin (TBIL) ＞ 34.2 μmol/L occurred earlier than those in group A (P ＜ 0.05)and there were more patients with abnormal creatinine and arterial oxygen and those abnormalities occurred earlier than those in group A (P ＜0.05).The maximum value of ALT,TBIL,creatinine,amylase (AMS)and CK-MB in the group B were higher than those in group A (P ＜ 0.05),the lowest value of PaO2 (＜ 60mm Hg) in group B were lower than that in group A (P ＜ 0.05).Conclusions The early repeated HP can delay organ injury after acute paraquat poisoning and reduce the extent of injure,giving ample time to get advanced treatment measures to improve the prognosis of patients. Key words: Hemoperfusion; Paraquat; Poisoning

Proteomic analysis of changes in protein expression in serum from animals exposed to paraquat

Paraquat (PQ) poisoning remains a major public health concern in many countries. Extensive research has focused on finding early diagnostic biomarkers of acute PQ poisoning. In order to investigate the characterization of diagnostic biomarkers in PQ poisoning, we utilized proteomic analysis using serum from rats exposed to PQ, and we identified 8 differentially expressed proteins from over 500 protein spots. The expression of apolipoprotein E (ApoE), preprohaptoglobin (Pphg), a precursor of haptoglobin (Hp), and complement component 3 (C3) proteins was greatly induced by PQ exposure while the expression of fibrinogen γ-chain (FGG) and Ac-158 was dramatically reduced. To further investigate the possibility of ApoE, Pphg and FGG as useful diagnostic biomarkers of PQ poisoning, western blot and qRT-PCR analyses were conducted using cell lines as well as rat and human sera. The expression levels of ApoE, Hp and FGG were significantly altered in the presence of PQ in both rat and human serum suggesting that these proteins may be appropriate candidate molecular biomarkers for the early diagnosis of acute PQ intoxication.

Central nervous system damage due to acute paraquat poisoning: A neuroimaging study with 3.0 T MRI

Paraquat (PQ) is an organic heterocyclic herbicide that is widely used throughout the world. Epidemiological and neuropathological studies have shown that chronic exposure to PQ increases the risk of Parkinson's disease. Patients with acute PQ poisoning show damage to the lungs, liver, and kidneys, and some also show symptoms of central nervous system (CNS) toxicity. However, few studies have focused on the acute neurotoxic changes caused by PQ. Dynamic pathological changes in the human brain cannot be explored in animal models. Thus, to elucidate the impact of acute PQ poisoning on the CNS, neuroimaging studies of poisoned victims, and especially survivors, should be performed. This study reports the first application of magnetic resonance imaging (MRI) techniques on patients with acute PQ poisoning, including survivors. We found significant abnormal signals in the brains of two patients during the acute post-poisoning phase. Using susceptibility weighted imaging (SWI), we documented changes in the corrected phase values for the extrapyramidal ganglia of survivors, and these values correlate with excessive iron deposition. Our diffusion tensor imaging (DTI) results were suggestive of microstructural changes in the extrapyramidal ganglia and hippocampus after PQ poisoning. These neuroimaging results provide an indirect demonstration that acute PQ neurotoxicity exerts a sustained effect during the acute and recovery stages of poisoning.

The Value of Plasma Paraquat Concentration in Predicting Therapeutic Effects of Haemoperfusion in Patients with Acute Paraquat Poisoning

ObjectiveThis study was aimed to analyze the scavenging effect of haemoperfusion on plasma paraquat (PQ) and to evaluate the clinical significance of PQ examination in the treatment of patients with acute paraquat poisoning.Methods85 patients with acute paraquat intoxication by oral ingestion were admitted in West China Hospital from Jun, 2010 to Mar, 2011. A standardized therapeutic regimen including emergency haemoperfusion was given on all subjects. A total of 91 whole blood samples were taken before (0h), underway (1h after haemoperfusion beginning) and at the end (2h) of the haemoperfusion therapy. The clearance rate was calculated and related factors were analyzed.ResultsAs heamoperfusion was going on, the plasma paraquat concentration of the patients kept falling down. After 1 hour of haemoperfusion, the average clearance rate (R1) was 37.06±21.81%. After 2 hours of haemoperfusion, the average clearance rate (R2) was 45.99±23.13%. The average of R1/R2 ratio was 76.61±22.80%. In the high paraquat concentration group (plasma paraquat concentration (C0) >300 ng/mL), both the averages of R1 and R2 were significantly higher than those of the low paraquat concentration group (C0≤200 ng/mL) (p<0.05), and there was no significant difference of R1/R2 between these two groups (p>0.05).ConclusionsThe dynamic monitoring of plasma PQ concentration was not only critical in the clinical evaluation but also helpful in guiding the treatment of patients with acute PQ intoxication. Haemoperfusion can effectively eliminate paraquat from the plasma in patients with high initial plasma PQ concentration, while in patients with low initial plasma PQ concentration (<200 ng/ml), the clearance effect of harmoperfusion was very limited. Increasing HP time might improve the overall clearance rate of HP on plasma PQ yet decrease the elimination efficiency of HP, while repeated HP treatment was helpful against the rebound phenomena.

The relationship between HIF-1α expression and the early lung fibrosis in rats with acute paraquat poisoning

To explore the role of hypoxia-inducible factor 1alpha (HIF-1α) in early lung fibrosis of rats with acute paraquat (PQ) poisoning. Forty eight healthy SD rats were randomly divided into control group (6 rats) and paraquat poisoning group (42 rats). Control group was exposed to 1 ml normal solution by gastric gavage. The paraquat group was exposed to 1 ml paraquat solution (50 mg/kg) by gastric gavage for 2, 6, 12, 48, 72 and 120 h, respectively. The arterial blood gas analysis (PaO(2)) was detected. The pathological examinations of lung tissues were performed by HE and Mason staining. HIF-1α in lung tissues were measured by immunofluorescence. Western blot assay was used to detect the expression levels of HIF-1α protein in lung tissues. PaO2 of rats exposed to paraquat for 72 h was (62.33 ± 0.22) mm Hg, which was significantly lower than that (96.00 ± 5.20) of control group (P < 0.05). Pathological examination by HE staining indicated that the acute diffuse lesion appeared in the alveolar capillary endothelium, epithelia and interstitial tissues, and there was the inflammatory cell infiltration in the alveolar of rats exposed to paraquat at 2 h after exposure. At 12 h after exposure, the interstitial edema in lung tissues of rats decreased and the alveolar space became narrow. At 120 h after exposure, there were the alveolar structure derangement, abundant cicatrix, more fibroblasts and peripheral inflammation absorption. Pathological examination by Masson staining showed that there was obvious collagen deposition in the alveolar epithelia at 2h after exposure, the increased collagen fibrosis at 24 and 48 h after exposure and the obvious damage of alveolar tissues or much more fibrous connective tissue deposition at 120 h after exposure. The results of western blot and immunofluorescence assays exhibited that the expression levels of HIF-1α in lung tissues at 2, 24 and 48 h after exposure significantly increased, as compared with control group (P < 0.05), but there were no significant differences of HIF-1α expression among sub-groups at different time points after exposure. The results of present study shown that there were the pulmonary fibrosis and increased expression of HIF-1α in acute PQ poisoning rats at the early stage, and HIF-1α may be associated with pulmonary fibrosis.

Response to the Letter by Dr. Farzad Gheshlaghi

Dear Editor, We would like to respond to the letter by Dr. Farzad Gheshlaghi on the article entitled “Effects of Deliberate Ingestion of Organophosphate or Paraquat on Brain Stem Auditory-Evoked Potentials (BAEP)” The study group was interested in finding out whether there is any clinically significant lesion in the auditory pathway following acute ingestion of organophosphate (OP) or paraquat (PQ). History and examination of all the patients confirmed that they had acute ingestion of OP or PQ. For our OP patients, quantification of plasma cholinesterase (ChE) activity within 12 h of ingestion was available in 34/70. There was no statistically significant correlation of ChE activity with 1-111, 111-V, and 1-V latencies (Table 1). Table 1 Correlation of ChE activity with 1-111, 111-V, and 1-V latencies of BAEP PQ is extremely toxic with a 65% fatality following suicidal ingestion. We assessed BAEP of PQ survivors. Since PQ is rapidly absorbed from gastrointestinal tract and has high affinity for tissue, early sample collection to determine plasma PQ levels is required to estimate severity of ingestion. We were unable to do this, but all the patients in the study had positive urine paraquat to sodium dithionite test. Nevertheless, further studies with the assessment of auditory threshold and serial BAEP in acute OP or PQ poisoning are needed. We thank Dr. Gheshlaghi for his interest and comments.

Effects of hemoperfusion on oxidative stress, matrix metalloproteinases and their inhibitors in acute paraquat poisoning rabbits

To observe the effects of hemoperfusion on oxidative stress status and the levels of matrix metallo proteinase (MMP-2, MMP-9), tissue inhibitor of metalloproteinase (TIMP-1) in lungs, livers and kidneys in paraquat poisoning rabbits, and to explore the mechanism of therapeutic effects induced by HP on acute paraquat poisoning. Seventy eight rabbits were randomly divided into normal control group (N group, n=6), exposure groups (PQ group, n=24), hemoperfusion treatment group (HP treatment group, n= 24) and blank control group (HP group, n=24). The PQ, HPQ and HP groups were divided into 4 observation time groups (1, 3, 7 and 21 d). N group was exposed to 5 ml normal saline and PQ group was exposed to 50 mg/kg PQ by oral gavage. In 1 h after PQ exposure, HPQ group was exposed to the activated carbon hemoperfusion for 2 h. The content or activity of MDA, SOD and GSH-Px in lungs, livers and kidneys were detected, the expression levels of MMP-2, MMP-9 and TIMP-1 were measured with immunohistochemical SP method for all groups. The contents of MDA in lungs, livers and kidneys of PQ and HPQ groups decreased and the activities of SOD and GSH-Px in lungs, livers and kidneys of PQ and HPQ groups increased with observation time. The expression levels of MMP-2, MMP-9 and TIMP-1 in PQ and HPQ groups enhanced on the first day, PQ group was most obvious. Along with the observation time extended, all kinds of positive expression were still high. Compared with normal control group, the activities of serum SOD and GSH-Px in PQ and HPQ groups declined significantly, but the contents of serum MDA increased; the expression levels of MMP-2, MMP-9 and TIMP-1 in lung, liver and kidney tissues increased obviously, the ration between MMP-9 and TIMP-1 significantly increased (P < 0.05). Compared with PQ group, the activities of SOD and GSH-Px in HPQ group significantly increased, the content of MDA declined, the expression levels of MMP-2, MMP-9 and TIMP-1 in lung, liver and kidney tissues declined obviously, the ration between MMP-9 and TIMP-1 significantly declined, but higher than N group, the differences were statistically significant (P < 0.05). The oxidative stress and MMPs may be involved in the pathogenesis of tissue injuries induced by paraquat. The treatment with HP could obviously reduce oxidative stress and the expression levels of MMP-2, MMP-9 and TIMP-1, enhance the ration between MMP-9 and TIMP-1. So HP treatment could play a role in rescuing the PQ poisoning and protecting the organs function.