A 20-year-old male patient was admitted in our department 14 h after paraquat poisoning at the dose of about 50 mL. The patient underwent intensive hemoperfusion for 2 h (3 times a day) for 9 consecutive days and received continuous renal replacement therapy (CRRT) in the mode of continuous veno-venous hemofiltration (CVVH) for 10 consecutive days in addition to routine medications. The biochemical indexes were monitored during the therapy. After the treatment, paraquat concentrations in the blood and urine were decreased, and the patient's urine volume (UV) increased, serum creatinine (Cr) level decreased, and the oxygenation index became normal. Dynamic CT scan showed no obvious pulmonary fibrosis. The patient was followed up for 6 months after discharge and no complaint of discomforts was reported. This case suggests that early intensive hemoperfusion and long-term CVVH may help improve the prognosis after paraquat poisoning.
Blood Gas Analysis ; Blood Pressure ; Body Fluids ; Hemofiltration ; Hemoperfusion ; Humans ; Male ; Paraquat ; poisoning ; Poisoning ; therapy ; Prognosis ; Renal Dialysis ; Young Adult

Chemistry Techniques, Analytical ; instrumentation ; Herbicides ; analysis ; Humans ; Paraquat ; analysis

OBJECTIVETo observe the best dose of methylprednisolone improving lung injury in swine with paraquat intoxication.

METHODSAcute lung injury (ALI/ARDS) model was made by an intraperitoneal injection of a large dose of 20%PQ solution20 millilitres in swine. Then 24 swine were randomly divided into 4 groups: exposed PQ control group, 5 mg/kg of methylprednisolone group, 15 mg/kg of methylprednisolone group, 30 mg/kg of methylprednisolone group. All groups were based on the conventional rehydration for intervention, Arterial blood samples were collected before modeling and 0, 12, 24, 36 hours after different processing for blood gas analysis. At the same time heart rate (HR), mean arterial pressure (MAP), extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) were measured by using PICCO (pulse indicator continuous cardiac output), lung tissue was obtained by punctureneedle to produce lung biopsy, then observe the pathological changes of lung tissue in the microscope.

RESULTS1. Comparison between groups: there is no significant difference about extravascular lung water index (EVLWI) and semi-quantitative score of lung tissue pathology in four groups (P > 0.05) before modeling, so is t0, there is significant difference at about extravascular lung water index and semi-quantitative score of lung tissue pathology 12 h, 24 h and 36 h after different processing (P < 0.05). Within the group: EVLWI and semi-quantitative score of Lung tissue pathology in four groups significantly increased when the model was made (P < 0.05), after different processing, EVLWI and semi-quantitative score of Lung tissue pathology in exposed PQ control group kept going up, in other three groups, EVLWI and semi-quantitative score of lung tissue pathology went down first and then went up, there is significant difference compared with t0 (P < 0.05). 2. Comparison between groups: there is no significant difference about oxygenation index in four groups (P > 0.05) before modeling, so is t0, there is significant difference about oxygenation at 12 h, 24 h and 36 h after different processing (P < 0.05). Within the group: oxygenation index in four groups significantly decreased when the model was made (P < 0.05), after different processing, oxygenation index in exposed PQ control group kept going down, in other three groups, it showed a downward trend after the first rise, there is significant difference compared with t0 (P < 0.05). 3. After medication for 36h, correlation analysis showed that EVLWI were negatively associated with oxygenation index (r = -0.427, P = 0.022) and positively associated with semi-quantitative score of Lung tissue pathology (r = 0.903, P = 0.034).

CONCLUSIONMethylprednisolone can obviously relieve lung injury caused by paraquat poisoning and improve oxygenation. After the model was made, within 24 hours, 30 mg/kg of methylprednisolone have advantage for the PQ poisoning swine, but 15mg/kg of methylprednisolone is best for improving lung injury induced by paraquat intoxication within 24 hours to 36 hours.

Acute Lung Injury ; chemically induced ; drug therapy ; Animals ; Blood Gas Analysis ; Capillary Permeability ; Extravascular Lung Water ; Heart Rate ; Lung ; Lung Injury ; Methylprednisolone ; administration & dosage ; therapeutic use ; Paraquat ; toxicity ; Swine

Although 4,4'-diaminodiphenylsulfone (DDS, dapsone) has been used to treat several dermatologic conditions, including Hansen disease, for the past several decades, its mode of action has remained a topic of debate. We recently reported that DDS treatment significantly extends the lifespan of the nematode C. elegans by decreasing the generation of reactive oxygen species. Additionally, in in vitro experiments using non-phagocytic human fibroblasts, we found that DDS effectively counteracted the toxicity of paraquat (PQ). In the present study, we extended our work to test the protective effect of DDS against PQ in vivo using a mouse lung injury model. Oral administration of DDS to mice significantly attenuated the lung tissue damage caused by subsequent administration of PQ. Moreover, DDS reduced the local expression of mRNA transcripts encoding inflammation-related molecules, including endothelin-1 (ET-1), macrophage inflammatory protein-1alpha (MIP-1alpha), and transforming growth factor-beta (TGF-beta). In addition, DDS decreased the PQ-induced expression of NADPH oxidase mRNA and activation of protein kinase Cmicro (PKCmicro). DDS treatment also decreased the PQ-induced generation of superoxide anions in mouse lung fibroblasts. Taken together, these data suggest the novel efficacy of DDS as an effective protective agent against oxidative stress-induced tissue damages.
Animals ; Cells, Cultured ; Chemokine CCL3/drug effects/metabolism ; Dapsone/*administration & dosage ; Endothelin-1/drug effects/metabolism ; Fibroblasts/drug effects ; Herbicides/*antagonists & inhibitors/toxicity ; Lung Injury/chemically induced/*prevention & control ; Male ; Mice ; Mice, Inbred BALB C ; Oxidative Stress ; Paraquat/*antagonists & inhibitors/toxicity ; Protective Agents/*administration & dosage ; Protein Kinase C/genetics/metabolism ; Superoxides/analysis ; Transforming Growth Factor beta/drug effects/metabolism

OBJECTIVETo investigate the protective effects of the tert-butylhydroquinone (tBHQ) pretreatment on neurotoxicity and oxidative stress induced by paraquat (PQ) in PC12 cells.

METHODSCytotoxicity of PC12 cells was measured by MTT assay, following the PC12 cells treatment with different concentrations of 100, 300 micromol/L PQ for 24 h and 48 h. PC12 cells were pretreated with or without 40 micromol/L tBHQ for 4 h, PC12 cells were exposed to PQ at the doses of 0, 100, 300 micromol/L for 24 h and 48 h, respectively. The viability of PC12 cells was measured by MTT assay, the apoptosis rates of PC12 cells were detected by flow cytometry (FCM) and the malondialdehyde (MDA) levels of PC12 cells were examine by thiobarbituric acid (TBA) method.

RESULTSWhen the exposure doses of PQ were 100 and 300 micromol/L for 24 h, the viability of PC12 cells pretreated with tBHQ was significantly higher than that of PC12 cells only exposed to PQ (P < 0.05 or P < 0.01). When the exposure dose of PQ was 100 micromol/L for 48 h, the viability of PC12 cells pretreated with tBHQ was significantly higher than that of PC12 cells only exposed to PQ (P < 0.01). When the exposure doses of PQ were 100 and 300 micromol/L for 24 h, the apoptosis rates and MDA levels of PC12 cells pretreated with tBHQ were significantly lower than those of PC12 cells only exposed to PQ (P < 0.05 or P < 0.01).

CONCLUSIONStBHQ pretreatment can reduce the cytotoxicity, apoptosis and oxidative stress induced by PQ in PC12 cells.

Animals ; Apoptosis ; drug effects ; Cell Survival ; drug effects ; Hydroquinones ; pharmacology ; Oxidative Stress ; drug effects ; PC12 Cells ; Paraquat ; toxicity ; Rats ; Reactive Oxygen Species ; analysis

To investigate the effects of reactive oxygen species (ROS) on tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) plasma levels, and their possible implications on clinical outcome, we measured tPA and PAI-1 levels in 101 patients with acute paraquat (PQ) intoxication. The control group consisted of patients who ingested non-PQ pesticides during the same period. tPA and PAI-1 levels were higher in the PQ group than in the controls. PQ levels were significantly correlated with ingested amount, timelag to hospital, tPA level, and hospitalization duration. tPA levels were correlated with PAI-1, fibrin degradation product (FDP), and D-dimer. D-dimer levels were lower in the PQ group than in the controls. Univariate analysis indicated the following significant determinants of death: age, ingested amount, PQ level, timelag to hospital, serum creatinine, lipase, pH, pCO2, HCO3-, WBC, FDP, PAI-1, and tPA. However, multivariate analysis indicated that only PQ level was significant independent factor predicting death. In conclusion, tPA and PAI-1 levels were higher, while D-dimer levels were lower in the PQ group than in the controls, implying that ROS stimulate tPA and PAI-1, but PAI-1 activity overrides tPA activity in this setting. Decreased fibrinolytic activity appears to be one of the clinical characteristics of acute PQ intoxication.
Acute Disease ; Adult ; Aged ; Female ; Fibrin Fibrinogen Degradation Products/analysis ; Herbicides/blood/*poisoning ; Humans ; Male ; Middle Aged ; Paraquat/blood/*poisoning ; Plasminogen Activator Inhibitor 1/*blood ; Reactive Oxygen Species/metabolism ; Risk Factors ; Tissue Plasminogen Activator/*blood ; Tomography, X-Ray Computed

Biocompatible Materials ; analysis ; Chromatography ; methods ; Chromatography, Gas ; methods ; Chromatography, Liquid ; methods ; Paraquat ; analysis ; Pesticide Residues ; analysis

Air Pollutants ; analysis ; Chromatography, High Pressure Liquid ; methods ; Paraquat ; analysis ; Workplace

BACKGROUNDParaquat (PQ; 1,1'-dimethyl-4,4'-bipyridinium), a widely used herbicide, has been repeatedly suggested as a potential etiologic factor for the development of Parkinson's disease (PD), owing to its structural similarity to the known dopaminergic neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This study aimed to observe the influence of paraquat on nigrostriatal dopaminergic neurons in C57BL/6 mice.

METHODSA total of 24 male C57BL/6 mice were assigned randomly to 3 groups: control group (treated by saline), PQ treated group, and MPTP treated group. Mice in PQ treated group were taken orally with PQ (10 mg/kg) daily for four months. Locomotor activity was measured. Level of dopamine (DA) and its metabolites levels in the striatum were measured by high-performance liquid chromatography with an electrochemical detector (HPLC-ECD), and tyrosine hydroxylase (TH) positive neurons were detected by using immunohistochemistry. At the same time, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and the content of malondialdehyde (MDA) in substantia nigra were measured by spectrophotometry. mRNA expression of dopamine transporter (DAT) in dopaminergic neurons of substantia nigra was also determined by reverse transcription (RT)-PCR technique.

RESULTSLocomotor activities were significantly impaired in the PQ treated group. Level of DA and its metabolites levels in the striatum were declined. The activities of SOD and GSH-PX were decreased, and the content of MDA was increased in PQ treated mice compared with that in control group. Numbers of TH positive neurons and the mRNA expression of DAT in substantia nigra of mice were also decreased after PQ taken orally for four months.

CONCLUSIONSThe present study suggests that chronic oral administration of PQ could trigger dopaminergic neuron degeneration. Oxidative stress could be involved in the pathogenic mechanism of PD induced by PQ.

Administration, Oral ; Animals ; Behavior, Animal ; drug effects ; Corpus Striatum ; drug effects ; Dopamine ; analysis ; metabolism ; Dopamine Plasma Membrane Transport Proteins ; analysis ; genetics ; Glutathione Peroxidase ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Oxidative Stress ; Paraquat ; toxicity ; Parkinson Disease ; etiology ; RNA, Messenger ; analysis ; Substantia Nigra ; drug effects ; Superoxide Dismutase ; metabolism

PURPOSE: To date, paraquat poisoning has almost universally resulted in unfavorable outcomes, and it has become a big issue in clinical toxicology. Current efforts to overcome its toxicity have focused on drugs with anti-oxidant capacity such as ascorbic acid in order to combat over-production of reactive oxygen species (ROS) by paraquat radicals, which are mainly induced by NADPH-cytochrome P450 reductase. Unfortunately, this strategy of treatment has not yielded satisfactory results. In search of a new approach to cope with PQ toxicity, we developed an in vitro culture model of cells resistant to lethal doses of PQ, and we then investigated resistance mechanisms using DNA microarray technology, a tool for simultaneously measuring a number of gene expression changes. METHODS: This experiment was conducted in vitro using the hepatocelluar carcinoma cell line (HepG2) to assay xenobitotics metabolism. We induced resistant of these cells to up to 100 uM PQ by treating with escalating doses of PQ for about 5 months. Cytotoxicity was studied using the MTT method, and optical density was measured at 540 nm using an ELISA reader. We examined morphological changes in cells after drug treatment using an inverted microscope, and we investigated gene expression profiles in control and resistant cells by use of DNA microarray. RESULTS: Results of MTT assays indicated that resistant cells showed relatively high survivals against a 100 mM dose, but that the control group had zero percents of survival at a 1 mM dose. In the comparing gene expression levels between the control group and the resistant group, 6,717 genes found to be differentially expressed. In the analysis of anti-apoptosis genes in particular, the resistant group showed more expression of genes with anti-apoptotic functions than did the control group. In examining the expression of cytochrome P450 genes related to xenobiotic metabolism and PQ radical induction, expression of the cytochrome P450 1B1 gene was significantly higher in the resistant group than in the control group. CONCLUSION: Although cytochrome P450 is known to be responsible for redox cycling of PQ as an electron transferor, this study suggest that up-regulation of the cytochrome P450 1B1 gene can corelate with PQ resistance. Therefore, induction of cytochrome P450 1B1 can be a new therapeutic approach to reduce PQ toxicity through actual PQ degradation, rather than simply through neutralization of ROS.
Ascorbic Acid ; Cell Line ; Cytochrome P-450 Enzyme System ; DNA ; Electrons ; Enzyme-Linked Immunosorbent Assay ; Gene Expression ; Hep G2 Cells ; NADPH-Ferrihemoprotein Reductase ; Oligonucleotide Array Sequence Analysis ; Oxidation-Reduction ; Paraquat ; Phosphatidylethanolamines ; Reactive Oxygen Species ; Toxicology ; Transcriptome ; Up-Regulation