To explore the dose-effect relationship between vitamin C and paraquat (PQ) poisoning rats.
 Methods: A total of 40 Sprague-Dawley (SD) rats were randomly divided into 4 groups: a control group, a PQ poisoning group, a vitamin C group 1 and a vitamin C group 2 (n=10 in each group). 150 mg/kg PQ was perfused into rat stomach to establish PQ poisoning rat model. In PQ poisoning group, 30 mg/kg methylprednisolone and 2.5 mg/kg cyclophosphamide were injected peritoneally on the basis of PQ poisoning rat model. In vitamin C1 and C2 group, vitamin C was injected at a dosage of 5 or 500 mg/kg, respectively. The control group only received normal saline (NS). The malondialdehyde (MDA), liver and kidney function as well as arterial blood gas in the blood were examined 36 h later. At the end, the rats were killed and took the liver tissues for pathological examination and weight ratio calculation. The glutathione peroxidase (GSH-PX), ctychrome C (Cyt C) in the liver tissues were detected by chromatometry, and the Bcl-2 was detected by Western blot.
 Results: Compared with the PQ poisoning group, the MDA and Cyt C were decreased, the GSH-PX was increased, and liver and kidney functions were improved in the vitamin C group 1 (all P<0.01); but in the vitamin C group 2, the MDA increased and liver/kidney functions were impaired (all P<0.01). The expression of Bcl-2 in the PQ poisoning group was lower than that in the control group; compared with the PQ poisoning group, it was increased in the vitamin C1 group, while it was decreased in the vitamin C group 2 (both P<0.01). There was no obvious difference in the lung function, wet/dry weight ratio and pathological changes between the poisoning group and experimental groups (all P>0.05).
 Conclusion: Vitamin C at the low dose shows a certain degree of protection for the liver and kidney in the PQ poisoning rats model through it antioxidative activity and anit-apoptosis activity, while vitamin C at the high does may promote oxidation. Meanwhile, vitamin C doesn't show protective effect on lung in the PQ poisoning rats.
Animals ; Apoptosis ; drug effects ; Ascorbic Acid ; administration & dosage ; pharmacology ; Cytochromes c ; drug effects ; metabolism ; Dose-Response Relationship, Drug ; Glutathione Peroxidase ; drug effects ; Kidney ; drug effects ; pathology ; physiopathology ; Lung ; drug effects ; pathology ; physiopathology ; Malondialdehyde ; metabolism ; Paraquat ; toxicity ; Protective Agents ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Vitamins

OBJECTIVETo explore the clinical efficacy of early application of sequential gastrointestinal lavage in patients with acute paraquat poisoning by analyzing the clinical data of 97 patients.

METHODSA total of 97 eligible patients with acute paraquat poisoning were divided into conventional treatment group (n = 48) and sequential treatment group (n = 49). The conventional treatment group received routine gastric lavage with water. Then 30 g of montmorillonite powder, 30 g of activated charcoal, and mannitol were given to remove intestinal toxins once a day for five days. The sequential treatment group received 60 g of montmorillonite powder for oral administration, followed by small-volume low-pressure manual gastric lavage with 2.5%bicarbonate liquid. Then 30 g of activated charcoal, 30 g of montmorillonite powder, and polyethylene glycol electrolyte lavage solution were given one after another for gastrointestinal lavage once a day for five days. Both groups received large doses of corticosteroids, blood perfusion, and anti-oxidation treatment. The levels of serum potassium, serum amylase (AMY) alanine aminotransferase (ALT), total bilirubin (TBIL), blood urea nitrogen (BUN), creatinine (Cr), lactate (Lac), and PaO₂of patients were determined at 1, 3, 5, 7, and 10 days. Laxative time, mortality, and survival time of dead cases were evaluated in the two groups.

RESULTSThe incidence rates of hypokalemia (<3.5 mmol/L) and AMY (>110 U/L) were significantly lower in the sequential treatment group than in the conventional treatment group (P < 0.05). There were no significant differences in the incidence of ALT (>80 U/L), TBIL (>34.2 µmol/L), BUN (>7.2 mmol/L), and Cr (>177 µmol/L) between the two groups (P>0.05). However, the highest levels of ALT, TBIL, BUN, Cr, and Lac were significantly lower in the sequential treatment group than in the conventional treatment group (P < 0.05). Moreover, the sequential treatment group had significantly lower incidence of PaO₂(<60 mmHg), shorter average laxative time, lower mortality, and longer survival time of dead cases than the conventional treatment group (P < 0.05).

CONCLUSIONThe early application of sequential gastrointestinal lavage can shorten laxative time, alleviate organ damage in the liver, kidney, lung, and pancreas, reduce mortality, and prolong the survival time of dead cases in patients with acute paraquat poisoning.

Acute Disease ; Bentonite ; administration & dosage ; Bilirubin ; Blood Urea Nitrogen ; Charcoal ; Combined Modality Therapy ; Creatinine ; Gastric Lavage ; methods ; Humans ; Liver ; Paraquat ; poisoning ; Poisoning ; therapy ; Treatment Outcome

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

Acute Disease ; Adolescent ; Adult ; Aged ; Cyclophosphamide ; administration & dosage ; therapeutic use ; Female ; Hemoperfusion ; Humans ; Male ; Methylprednisolone ; administration & dosage ; therapeutic use ; Middle Aged ; Paraquat ; poisoning ; Renal Dialysis ; Retrospective Studies ; Young Adult

OBJECTIVETo observe the effects of Nrf2 gene expression induced by RU486 at different doses on A549 cell damage induced by paraquat (PQ).

METHODSAfter A549 cells transfected with Ad-RUNrf2 were treated by RU486 at the doses of 10(-10), 10(-9), 10(-8) and 10(-7) mol/L for 6 h, A549 cell cultures were exposed to 10(-3) mol/L of PQ for 48 h. Then qRT-PCR and EMSA assays were used to detect the expression of Nrf2 gene, and qRT-PCR and ELISA assays were utilized to measure the effects of Nrf2 gene on the expression of the inflammatory cytokines IL-6, IL-10 and TNF-α, apoptotic factors Caspase-3, Caspase-9 and Cytochrome C. The oxidation factors (CAT and MDA protein contents) were observed by Chemical Colorimetric Analysis.

RESULTSNrf2 gene relative expression and protein contents increased with RU486 concentrations, and the above expression was the highest when the concentration of RU486 was 10(-7) mol/L, which was significantly higher than those in control and PQ exposure groups (P < 0.01 or P < 0.05). The relative gene expression and protein expression of IL-6 and TNF-α enhanced with the reduced concentrations of RU486, which were the lowest when RU486 concentration was 10(-7) mol/L, as compared with control and PQ exposure groups (P < 0.01 or P < 0.05), while the change of IL-10 content was the opposite. The relative expression of Caspase3, Caspase9 and Cytochrome C genes also increased with the reduced concentrations of RU486, which were the lowest when RU486 concentration was 10(-7) mol/L, as compared with control and PQ exposure groups (P < 0.01 or P < 0.05). The content of CAT enhanced with RU486 concentration, which was the highest when RU486 concentration was 10(-7) mol/L, as compared with control and PQ exposure groups (P < 0.05). But the change of MDA content was the contrary.

CONCLUSIONNrf2 expression induced by RU486 can promote the balance of oxidation-antioxidation system in A549 cells and inhibit the inflammation and apoptosis factors, which has a protective effect on A549 cell injury induced by PQ.

Cell Line ; Gene Expression ; drug effects ; Humans ; Interleukin-10 ; metabolism ; Interleukin-6 ; metabolism ; Mifepristone ; administration & dosage ; pharmacology ; NF-E2-Related Factor 2 ; genetics ; Paraquat ; toxicity ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo explore the damages of paraquat to the learning and memory ability of developing mice and explore the possible mechanism involving oxidative stress.

METHODSEighty healthy Kunming mice in aged 21 days were divided into 4 groups randomly: a control group (distilled water) and three paraquat treatment groups. The doses of paraquat were 0.89, 2.67 and 8mg/kg body weight, respectively. Paraquat was administered orally in doses of 0.1 ml/10 g body weight, respectively, once a day and for 28 consecutive days. The Morris water maze test and the shuttling and avoid dark box test were used to detect the learning and memory abilities of mice. The levels of MDA and the activities of SOD and GSH-PX were detected according to the commercial kits manual using a microplate reader.

RESULTSMorris water maze test showed that the escape latency of mice after paraquat treatment (57.98 +/- 2.78, 62.35 +/- 3.18, 85.57 +/- 5.10) were significantly increase compared with the control (21.74 +/- 1.36), respectively (P < 0.05). There were good dose-response relationship (R = 0.8629, P < 0.05). The shuttling and avoid dark box test showed that initiative avoidance latency of mice after paraquat treatment (5.56 +/- 0.29, 6.08 +/- 0.22, 8.32 +/- 0.38) were significantly increase compared with the control (3.50 +/- 0.13), respectively (P < 0.05). There were good dose-response relationship (R = 0.9579, P < 0.05). The levels of MDA in serum of mice in paraquat treatment groups (2.67 and 8 mg/kg) (24.76 +/- 1.76, 31.10 +/- 4.57) and in hippocampus of mice in each paraquat treatment groups were significantly increase compared with the control (serum: 16.38 +/- 6.26, hippocampus: 1.93 +/- 0.39) (P < 0.05, respectively). The activities of SOD in serum and hippocampus of mice in each paraquat treatment groups were significantly decrease compared with the control (serum: 213.25 +/- 6.78, hippocampus: 197.36 +/- 6.37) (P < 0.05, respectively). The activities of GSH-PX in serum and hippocampus of mice in each paraquat treatment groups were significantly decrease compared with the control (serum: 583.47 +/- 11.23, hippocampus: 412.38 +/- 13.16) (P < 0.05, respectively).

CONCLUSIONParaquat can induce the oxidative damage in hippocampus, and then influence the learning and memory abilities of developing mice.

Animals ; Female ; Hippocampus ; drug effects ; metabolism ; Male ; Maze Learning ; drug effects ; Memory ; drug effects ; Mice ; Mice, Inbred Strains ; Oxidative Stress ; Paraquat ; administration & dosage ; toxicity ; Superoxide Dismutase ; metabolism

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

BACKGROUND/AIMS: Based on preliminary in vitro data from a previous study, we proposed that 50 mg/kg glutathione (GSH) would be adequate for suppressing reactive oxygen species in patients with acute paraquat (PQ) intoxication. METHODS: Serum levels of reactive oxygen metabolites (ROM) were measured before and after the administration of 50 mg/kg GSH to each of five patients with acute PQ intoxication. RESULTS: In one patient, extremely high pretreatment ROM levels began to decrease prior to GSH administration. However, in the remaining four cases, ROM levels did not change significantly prior to GSH administration. ROM levels decreased significantly after GSH administration in all cases. In two cases, ROM levels decreased below that observed in the general population; one of these patients died after a cardiac arrest at 3 hours after PQ ingestion, while the other represented the sole survivor of PQ intoxication observed in this study. In the survivor, ROM levels decreased during the first 8 hours of GSH treatment, and finally dropped below the mean ROM level observed in the general population. CONCLUSIONS: Treatment with 50 mg/kg GSH significantly suppressed serum ROM levels in PQ-intoxicated patients. However, this dose was not sufficient to suppress ROM levels when the PQ concentration was extremely high.
Adult ; Aged ; Antioxidants/administration & dosage ; Case-Control Studies ; Fatal Outcome ; Glutathione/*administration & dosage ; Herbicides/administration & dosage/poisoning ; Humans ; Male ; Middle Aged ; Paraquat/administration & dosage/*poisoning ; Pilot Projects ; Reactive Oxygen Species/*blood ; Time Factors ; Treatment Outcome

Adult ; Ambroxol ; administration & dosage ; therapeutic use ; Expectorants ; administration & dosage ; therapeutic use ; Female ; Glycoproteins ; therapeutic use ; Humans ; Lung ; pathology ; Lung Injury ; drug therapy ; pathology ; Male ; Paraquat ; poisoning ; Respiratory Distress Syndrome, Adult ; drug therapy ; etiology ; Retrospective Studies ; Young Adult

OBJECTIVEto develop a high performance liquid chromatography method (HPLC) for the determination of paraquat in rabbit plasma and study its toxicokinetics in rabbits.

METHODStwelve rabbits were randomly divided into 2 groups with giving oral and intravenous administration of paraquat at a single dose of 60 mg/kg and 6 mg/kg respectively. The plasma paraquat concentrations were determined by HPLC and calculated by DAS pharmacokinetics program.

RESULTSthe linear range of paraquat in plasma was 0.05 ∼ 50.00 mg/L (r = 0.9998). The relative recoveries of the assay were 99.41% ∼ 102.32%. The absolute recoveries of the assay were 83.72% ∼ 90.48%. Both the intra-day and inter-day validations were less than 10%. For oral administration, the toxicokinetics parameters of paraquat were as follows: Cmax (14.46 ± 2.35) mg/L, Tmax (1.63 ± 0.31) h, AUC(0-t) (177.61 ± 14.62) mg × h/L, AUC(0-∞) (182.24 ± 14.54) mg × h/L, While for intravenous administration, the toxicokinetics parameters of paraquat: Cmax (35.13 ± 5.53) mg/L, Tmax 0.05 h, AUC(0-t) (121.74 ± 12.30) mg × h/L, AUC(0-∞) (125.12 ± 12.17) mg × h/L, The difference of these parameters between the two groups had statistical significance (P < 0.05). The oral bioavailability was (14.66 ± 1.55)%.

CONCLUSIONthe oral bioavailability of paraquat is relatively low. The biological half life of paraquat is relatively long and there is no significant difference between oral administration and intravenous on biological half life. This method is simple, sensitive and accurate. It can be used for the investigation of paraquat in rabbits.

Administration, Oral ; Animals ; Biological Availability ; Chromatography, High Pressure Liquid ; Injections, Intravenous ; Male ; Paraquat ; blood ; pharmacokinetics ; toxicity ; Rabbits