Objective: To investigate the effects of duration, temperature and shake on paraquat (PQ) concentration in the blood of PQ-exposed rats during the specinen preservation and transportation. Methods: In March 2021, 60 SD male rats of Specific Pathogen Free class were randomly divided into low-dose group (10 mg/kg PQ) and high-dose group (80 mg/kg PQ). Each group was divided into 5 subgroups (normal temperature group, cold storage group, 37 ℃ storage group, shaking on normal temperature group and shaking on 37 ℃ group), six rats in each subgroup. The rats were given intraperitoneal injection of PQ, 1 h after exposure, the blood samples were obtained by cardiac extraction. After different interventions, the concentrations of PQ were detected and compared before and after the intervention in each subgroup. Results: In the shaking on 37 ℃ group, the results of PQ concentrations in PQ-exposed rats were significantly lower than those before the intervention (P<0.05). In the other subgroups, the results were not significantly different compared with before intervention (P>0.05) . Conclusion: The concentration of PQ in the blood of rats exposed to PQ was decreased by shaking for 4 hours at 37 ℃.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Paraquat/pharmacology* ; Lung

Allyl Compounds ; Animals ; Lung ; Male ; Paraquat/pharmacology* ; Poisons ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Sulfides

OBJECTIVEto study the oxidative stress of rats with acute paraquat poisoning and the intervention of Sodium Dimercaptopropane Sulfonate (NA-DMPS).

METHODSEighty male SD rats were randomizedly divided into: the normal control group (n=8), NA-DMPS control group (n=8), the PQ group (n=32, the rats were intraperitoneally injected with 1% PQ solution at the dosage of 20 mg/kg) and the NA-DMPS protected group (n=32). The rats in the groups of normal and NA-DMPS control were sacrificed 1d after administration of NS or NA-DMPS. And the rats in the PQ group and the NA-DMPS protected group were sacrificed at 6h, 1, 3, 7d after poisoning. Samples of serum, bronchoalveolar lavage fluid (BALF) and lung tissue were gathered. The MDA and CAT in serum, BALF and lung homogenate, the glutathione (GSH) in serum and BALF were measured. And the expression of Nuclear factor E2-related factor 2 (Nrf2) mRNA in lung was tested with RT-PCR.

RESULTSCompared with the normal control group, the activities of MDA and CAT in serum, BALF and lung homogenate are higher in both groups of PQ and NA-DMPS protected. And compared with the PQ group, the activities of MDA in serum, BALF and lung homogenate of the NA-DMPS protected group decreased significantly at 6h, 1d after poisoning, whereas the activities of CAT are higher at 6h, 1, 3d in serum and 1, 3d in BALF and lung homogenate (P<0.05 or P<0.001). The serum GSH at 6h, 3d of the NA-DMPS protected group [(730.07 +/- 16.23), (793.66 +/- 7.40)] were higher than those in the PQ group. And the BALF GSH at 1, 3d of the NA-DMPS protected group [(609.75 +/- 6.74), (631.83 +/- 12.03)] were also markedly higher than the PQ group (P<0.05 or P<0.001). The expression of NRF2 mRNA of the lung at 1, 3, 7d in the PQ group [(0.71 +/- 0.061), (1.023 +/- 0.158), (0.969 +/- 0.046)] and the NA-DMPS protected group [(1.005 +/- 0.06), (1.464 +/- 0.166), (1.066 +/- 0.191)] were significantly higher than those in the control groups. Compared with the PQ group, the expression of NRF2 mRNA of the lung increased markedly in the NA-DMPS protected group at 1, 3d (P<0.01).

CONCLUSIONNa-DMPS decreases the activity of MDA and increases the activity of CAT, GSH and the expression of Nrf2 mRNA. NA-DMPS can protected rats from PQ intoxication by improving the balance of redox reaction.

Acute Disease ; Animals ; Male ; Oxidative Stress ; drug effects ; Paraquat ; poisoning ; Rats ; Rats, Sprague-Dawley ; Unithiol ; pharmacology

To study the effect of exogenous oxygen, we added water solution of paraquat to 7 d cultures of Coriolus versicolor for the next 148 h. Enzyme exudation and biochemical process were investigated on the addition of paraquat. We found that compared with the control (without paraquat), the addition of 30 micromol/L paraquat stimulated the activity of manganese dependent peroxidase (MnP), lignin peroxidase (LiP), and laccases (Lac) 7, 2.5 and 1.3 times, respectively. Also, addition of paraquat enhanced activity of superoxide dismutase (SOD) and catalase (CAT) in the first 48 h. Impact of paraquat on ligninolytic enzymes was significant than that on antioxidant enzyme. Addition of paraquat enhanced phenolic compounds and formaldehyde of cultures too. And concentration of malondialdehyde was increased in the first 24 h. The results showed that addition of paraquat promoted oxidative stress, but the antioxidant systems of the fungal strain are sufficient to prevent mycelia from oxidative stress. As exogenous oxygen, paraquat might be a useful substrate in degradation of lignocellulose.
Fungi ; drug effects ; enzymology ; Lignin ; metabolism ; Oxidative Stress ; Paraquat ; pharmacology ; Peroxidases ; metabolism

No abstract available.
Animals ; Cyclophosphamide/*pharmacology ; Immunosuppressive Agents/*pharmacology ; Lung/*drug effects ; Lung Injury/*drug therapy ; Male ; *Paraquat ; Pulmonary Edema/*drug therapy

OBJECTIVETo investigate the expression of angiotensin converting enzyme (ACE) and ACE2 Gene in lung of paraquat poisoning rats and the protection of sodium dimercaptopropane sulfonate (Na-DMPS).

METHODSOne hundred SD male rats were randomly equally divided into 4 groups:normal control group (10 rats), drug control group (40 rats), paraquat poisoning group (40 rats) and drug intervention group(40 rats). The paraquat poisoning and drug intervention group rats were injected intraperitoneally by paraquat (20 mg/kg). The rats in drug intervention group rats were protected by intraperitoneal injection with Na-DMPS (200 mg/kg) 15 min before exposure of paraquat. Behavioral changes of the rats and histological changes of lung tissues under light microscope were observed. And the expression of ACE and ACE2 mRNA in lung tissues of rats both in paraquat poisoned group and drug intervention group were measured by RT-PCR at different time of 6 h, 24 h, 3 and 7 d after poisoning.

RESULTSThe poisoning symptoms of shortness of breath, cramps appeared and deteriorated progressively in rats after paraquat exposure and the protection of NA-DMPS could delay and reduce these symptoms significantly. Histological appearance of disorganization of pulmonary capillary and alveolus, exudation in alveolar space, pulmonary edema, severe bleeding, and inflammatory cells infiltration were obvious in lungs of rats after paraquat poisoning, whereas the histological changes were extenuated by protection of NA-DMPS. As compared with normal control group (NC group), the expressions of ACE, ACE2 mRNA in lung tissue decreased, and the lowest level of ACE mRNA expressions appeared at 24 h (0.457 +/- 0.262), on 3 d (0.385 +/- 0.179) after Paraquat exposure (P < 0.05), while lowest level of ACE2 mRNA expressions appeared on 3 d (0.415 +/- 0.247), 7 d (0.365 +/- 0.215) (P < 0.05). As compared with paraquat poisoned group, the expressions of ACE mRNA in lung tissue of rats in NA-DMPS protected group increased significantly at 24 h (0.739 +/- 0.558) and 3 d (0.749 +/- 0.414) (P < 0.05), while the expressions of ACE2 mRNA increased markedly on 3 d (0.584 +/- 0.345) and 7 d (0.493 +/- 0.292) (P < 0.05). But the expression of ACEmRNA and ACE2 mRNA in lungs had no statistical significance between normal control group and drug intervention group (P > 0.05).

CONCLUSIONThe expressions of ACE and ACE2 mRNA in lung tissue of the rats with paraquat poisoning are decreased. Na-DMPS can effectively improve the balance of RAS in local lung tissue and reduce the pathological changes of lung tissue, delay the poisoning symptoms and show protective effects for acute lung injury induced by paraquat.

Animals ; Lung ; drug effects ; enzymology ; Male ; Paraquat ; poisoning ; Peptidyl-Dipeptidase A ; biosynthesis ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Unithiol ; pharmacology

OBJECTIVETo investigate the 4-hydroxynonenal (4-HNE) expression changes and the impact of ulinastatin (UTI) METHODS: Seventy-two healthy Sprague-Dawley rats were randomly divided into three groups: the control group, poisoning group and treatment group, with 24 rats in each group. The model of lung injury was established by intragastric PQ (80 mg/kg) administration in poisoning group and treatment group, and 1 mL saline was administered intragastrically in the control group. The rats in treatment group were injected intraperitoneally with UTI (100 000 U/kg) 30 minutes after PQ administration, and the rats in the control group and poisoning group were intraperitoneally injected with the same volume of saline. After different treatments, the pathological changes and the expression of 4-HNE in lung tissue was detected in 12, 24, and 72 h in three groups.

RESULTSIn the poisoning group and treatment group, the expression of 4-HNE in lung tissue of rats were increased in 12 h after poisoning and reached the peak in 48 h; in 72 h after poisoning, the expression of 4-HNE in lung tissue were decreased, but they were still high. Compared with the control group, the expression of 4-HNE in lung tissue of rats were significantly increased in the poisoning group and treatment group (P < 0.05). And compared with the poisoning group, the expression of 4-HNE in lung tissue of rats were significantly decreased in the treatment group (P < 0.01). The pathological changes were observed, including alveolar capillary expansion, diffuse alveolar hemorrhage and alveolar inflammation cell infiltration, were found in lungs of rats in poisoning group and treatment group. There is no significant change in the control group. Compared with the control group, the expression of 4-HNE in lung tissue significantly increased in poisoning group and treatment group (P < 0.01), but the expression in treatment group was lower than in poisoning group (P < 0.01).

CONCLUSIONThe expression of 4-HNE increased in PQ intoxicated rats. UTI may reduce the expression of 4-HNE and reduce lung injury in PQ intoxicated rats.

Aldehydes ; metabolism ; Animals ; Glycoproteins ; pharmacology ; Lung ; drug effects ; metabolism ; pathology ; Lung Injury ; metabolism ; pathology ; Paraquat ; poisoning ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo observe the expressions of α-SMA, integrin α5 and fibronectin (Fn) in acute paraquat poisoned rats and the effect of PDTC. To investigate the mechanism of paraquat-induced pulmonary fibrosis.

METHODSSprague-Dawley rats were randomly divided into three experimental groups: Control group (6 rats), PQ group (36 rats) and PQ+PDTC group (36 rats). On the 1st, 3rd, the 7th, the 14th, the 28th and the 56th day after exposure, the protein expression of α smooth muscle actin (α-SMA) was evaluated by western blot. The mRNA levels of integrin α5 and fibronectin (Fn) were analyzed with real-time quantitative PCR (RT-PCR). Meanwhile, the lung pathological changes were observed and semi-quantified.

RESULTST With the time passing, the expression of α-SMA in PQ group increased gradually compared with control group (P < 0.05 or P < 0.01). The increasing extent was gently on the 3 rd, the 7 th day. While increasing extent was rapidly from the 28 th to the 56 th day. RT-PCR showed PQ significantly increased Fn mRNA level on all time points and increased integrin α5 mRNA level from the 7 rd to 56 th day compared with control group (P < 0.05 or P < 0.01). PDTC treatment significantly deceased α-SMA, Fn, and integrin α5 levels compared with PQ group in corresponding time points (P < 0.05 or P < 0.01) Noteworthy, in PQ+PDTC group, the occurrence of pathological changes were drastically attenuated and pathologic score significantly decreased (P < 0.05 or P < 0.01).

CONCLUSIONSα-SMA, integrin α5 and fibronectin could play an important role in the development of pulmonary fibrosis caused by paraquat poisoning. PDTC, asa strong NF-κB inhibitor, may inhibit NF-κB activity and further significantly decreased expressions of α-SMA, integrin α5 and fibronectin which were important part of ECM, leading to drastically attenuated pulmonary fibrosis. However, the mechanisms of PDTC intervention still remains to be explored.

Actins ; metabolism ; Animals ; Disease Models, Animal ; Fibronectins ; metabolism ; Integrin alpha5 ; metabolism ; Male ; Paraquat ; poisoning ; Pulmonary Fibrosis ; chemically induced ; metabolism ; Pyrrolidines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Thiocarbamates ; pharmacology

The effectiveness of several sulfhydryl compounds in the treatment of paraquat intoxication has been previously tested based on their antioxidant ability. However, practical guidelines for their clinical use remain to be determined. As a preliminary pharmacokinetic study on sulfhydryl compounds, we attempted to establish the optimal concentration of N-acetyl-L-cysteine, glutathione, superoxide dismutase, and catalase. We measured the antioxidant effect of these antioxidants in normal pooled plasma and on intracellular reactive oxygen species (ROS) induced by paraquat. N-acetyl-L-cysteine begins to suppress the production of ROS in plasma at concentrations as low as 5 mM, with the suppression being maximal at 40 mM. In the same way, glutathione increased the total antioxidant status in plasma at concentrations of 5-40 mM in a dose-dependent manner. Complete suppression of ROS in plasma induced by exposure to 500 micrometer paraquat for 40 min was observed when using 40 mM N-acetyl-L-cysteine and 5 mM glutathione. These concentrations are comparable with 50 units of catalase, which reduced ROS at concentrations of 5-100 units. Further pharmacokinetic study into the systemic administration of these antioxidants is necessary, using effective concentrations of 5-40 mM for both N-acetyl-L-cysteine and glutathione, and 1-50 units of catalase.
Acetylcysteine/*pharmacology ; Animals ; Antioxidants/pharmacokinetics/*pharmacology ; Ascorbic Acid/metabolism ; Catalase/metabolism ; Dose-Response Relationship, Drug ; Free Radical Scavengers/pharmacology ; Glutathione/metabolism/*pharmacology ; Human ; Mice ; NIH 3T3 Cells ; Paraquat/pharmacology ; Reactive Oxygen Species ; Serum/*drug effects ; Support, Non-U.S. Gov't

OBJECTIVE: To observe whether metformin (MET) inhibits transforming growth factor-β₁ (TGF-β₁)/Smad3 signaling pathway by activating adenosine activated protein kinase (AMPK), so as to alleviate the pulmonary fibrosis caused by paraquat (PQ) poisoning in mice. METHODS: Male C57BL/6J mice were randomly divided into the Control group, PQ poisoning model group (PQ group), MET intervention group (PQ+MET group), AMPK agonist group (PQ+AICAR group), and AMPK inhibitor group (PQ+MET+CC group), according to a random number table method. A mouse model of PQ poisoning was established by one-time peritoneal injection of 1 mL PQ solution (20 mg/kg). The Control group was injected with the same volume of normal saline. After 2 hours of modeling, the PQ+MET group was given 2 mL of 200 mg/kg MET solution by gavage, the PQ+AICAR group was given 2 mL of 200 mg/kg AICAR solution by intraperitoneal injection, the PQ+MET+CC group was given 2 mL of 200 mg/kg MET solution by gavage and then 1 mL complex C (CC) solution (20 mg/kg) was intraperitoneally injected, the Control group and PQ group were given 2 mL of normal saline by gavage. The intervention was given once a day for 21 consecutive days. The 21-day survival rate of ten mice in each group was calculated, and the lung tissues of remaining mice were collected at 21 days after modeling. The pathological changes of lung tissues were observed under light microscope after hematoxylin-eosin (HE) staining and Masson staining, and the degree of pulmonary fibrosis was evaluated by Ashcroft score. The content of hydroxyproline in lung tissue and oxidative stress indicators such as malondialdehyde (MDA) and superoxide dismutase (SOD) were detected. The protein expressions of E-cadherin, α-smooth muscle actin (α-SMA), phosphorylated AMPK (p-AMPK), TGF-β₁ and phosphorylated Smad3 (p-Smad3) in lung tissue were detected by Western blotting. RESULTS: Compared with the Control group, the 21 days survival rate was significantly reduced, lung fibrosis and Ashcroft score were significantly increased in PQ group. In addition, the content of hydroxyproline, MDA and the protein expressions of α-SMA, TGF-β₁ and p-Smad3 in lung tissue were significantly increased, while the activity of SOD and the protein expressions of E-cadherin and p-AMPK were significantly decreased in PQ group. Compared with the PQ group, the 21 days survival rates of mice were significantly improved in the PQ+MET group and PQ+AICAR group (70%, 60% vs. 20%, both P < 0.05). The degree of pulmonary fibrosis and the Ashcroft score were significantly reduced (1.50±0.55, 2.00±0.63 vs. 6.67±0.52, both P < 0.05). The content of hydroxyproline and MDA in lung tissue, as well as α-SMA, TGF-β₁ and p-Smad3 protein expressions were significantly reduced [hydroxyproline (mg/L): 2.03±0.11, 3.00±0.85 vs. 4.92±0.65, MDA (kU/g): 2.06±1.48, 2.10±1.80 vs. 4.06±1.33, α-SMA/GAPDH: 0.23±0.06, 0.16±0.06 vs. 1.00±0.09, TGF-β₁/GAPDH: 0.28±0.03, 0.53±0.05 vs. 0.92±0.06 p-Smad3/GAPDH: 0.52±0.04, 0.69±0.06 vs. 1.11±0.10, all P < 0.05], SOD activity and the protein expressions of E-cadherin and p-AMPK were significantly increased [SOD (μmol/g): 39.76±1.35, 33.03±1.28 vs. 20.08±1.79, E-cadherin/GAPDH: 0.91±0.08, 0.72±0.08 vs. 0.26±0.04, p-AMPK/GAPDH: 0.62±0.04, 0.60±0.01 vs. 0.20±0.04, all P < 0.05]. However, these protective effects of MET were inhibited by the addition of AMPK inhibitor CC solution. CONCLUSIONS MET can effectively alleviate the degree of pulmonary fibrosis in mice poisoned with PQ, and its mechanism may be related to the activation of AMPK and inhibition of TGF-β₁/Smad3 signaling pathway, which can be inhibited by AMPK inhibitor CC.
Mice ; Male ; Animals ; Pulmonary Fibrosis/drug therapy* ; Paraquat ; AMP-Activated Protein Kinases/pharmacology* ; Metformin/pharmacology* ; Hydroxyproline/pharmacology* ; Saline Solution ; Mice, Inbred C57BL ; Lung/metabolism* ; Transforming Growth Factor beta1/pharmacology* ; Cadherins ; Superoxide Dismutase