In this study, A549/PQ cells with moderate resistance to paraquat (PQ) were obtained by treating A549 cells with PQ, their growth rate was slowed down, the accumulation concentration of PQ and the levels of growth inhibition, injury and early apoptosis induced by PQ were significantly lower than those of parental A549 cells. Microarray screening and RT-qPCR detection found that Synaptotagmin-1 (SYT1) expression in drug-resistant cells was significantly increased, and PQ further enhanced its expression. After inhibiting SYT1 expression in A549/PQ cells, cell viability, intracellular PQ concentration and the expression of Bcl-2, SNAP25 and RAB26 were significantly reduced, while the mortality, early apoptosis rate and Bax expression were significantly increased. In vivo experiments also further showed that PQ promoted the expression of SYT1, SNAP25 and RAB26 in PQ-poisoned mice; when inhibiting SYT1 expression, PQ concentration in lung tissues was significantly increased, and the levels of lung injury and apoptosis were also significantly enhanced, while the expression of SNAP25 and RAB26 was significantly reduced. This indicates that PQ poisoning leads to compensatory up-regulation of vesicle transport related proteins such as SYT1 in vivo, thereby promoting PQ transmembrane transport, and then reducing the pulmonary accumulation of PQ and PQ-caused lung injury.

Mitochondrial dysfunction and oxidative stress are pathophysiologic mechanisms implicated in experimental models and genetic forms of Parkinson's disease (PD). Certain pesticides may affect these mechanisms, but no pesticide has been definitively associated with PD in humans.

Adaptation of higher plants to extreme environmental conditions is under complex regulation. Several small peptides have recently been described to modulate responses to stress conditions. The Small Paraquat resistance protein (SPQ) of Lepidium crassifolium has previously been identified due to its capacity to confer paraquat resistance to overexpressing transgenic Arabidopsis plants. Here, we show that overexpression of the closely related Arabidopsis SPQ can also enhance resistance to paraquat, while the Arabidopsis spq1 mutant is slightly hypersensitive to this herbicide. Besides being implicated in paraquat response, overexpression of SPQs enhanced sensitivity to abscisic acid (ABA), and the knockout spq1 mutant was less sensitive to ABA. Both Lepidium- and Arabidopsis-derived SPQs could improve drought tolerance by reducing water loss, stabilizing photosynthetic electron transport and enhancing plant viability and survival in a water-limited environment. Enhanced drought tolerance of SPQ-overexpressing plants could be confirmed by characterizing various parameters of growth, morphology and photosynthesis using an automatic plant phenotyping platform with RGB and chlorophyll fluorescence imaging. Our results suggest that SPQs can be regulatory small proteins connecting ROS and ABA regulation and through that influence responses to certain stresses.

Severity index and plasma paraquat (PQ) concentration can predict the prognosis of patients with PQ poisoning. However, the better parameter is yet to be systematically investigated and determined. Thus, we conduct this systematic review and meta-analysis to investigate the prognostic value of severity index and plasma PQ concentration in patients with PQ poisoning.

Paraquat (PQ; a widely used herbicide) exerts its harmful effect to human, mammals and microorganisms upon intracellular conversion to superoxide radical. Cellular responses against toxic paraquat remain not fully understood, especially on the adaptive metabolic changes as a consequence of oxidative burden. In this study, alterations of metabolic processes of Escherichia coli (E. coli) by paraquat were systematically investigated by two-dimensional gel electrophoresis (2-DE) in conjunction with peptide mass fingerprinting (PMF). In host cells, the first line mechanism was scrutinized by a remarkable induction of endogenous superoxide dismutase (E. coli SOD). The second line involved in the metabolic adaptation and compensation for energy production by up- or down-regulation of the enzymes implicated in glycolysis and tricarboxylic acid cycle. Notably, down-regulation of aconitase enzyme and changes of enzyme isoform from the acidic (pI~5.29) to the higher basidic form (pI~5.59) were detected. Meanwhile, up-regulation of fumarase approximately 4-5 folds were observed. Importantly, overexpression of human manganese superoxide dismutase (human Mn-SOD) in E. coli cells could in turn down-regulate the expression of fumarase enzyme. This observation was not found when the cells expressing human catalase were tested. Other mechanisms such as changes of purine nucleoside phosphorylase and protein transporters (D-ribose-binding protein and oligopeptide binding protein) were also accounted. However, among all the differentially expressed proteins, the fumarase enzyme is evidenced to be a major target responsible for superoxide-generating paraquat, which may further be applied as a potential biomarker for paraquat toxicity in the future.

Paraquat (PQ) intoxication causes thousands of mortalities every year, worldwide. Its pulmonary-targeted accumulation and the acute lung injury it subsequently causes, remain a challenge for detoxification treatment. A previous study has demonstrated that the upregulation of nuclear factor erythroid-2 related factor 2 (Nrf2) prevents PQ toxicity in cell line and murine models. As Nrf2 target genes include a group of membrane transporters, the current study assessed the protective mechanism exerted by Nrf2 against PQ toxicity and intracellular PQ accumulation via its effects on P-glycoprotein (P-gp), a downstream transporter of Nrf2. Adenovirus vectors containing the Nrf2 gene were transfected into A549 cells. Cell proliferation was assessed by Cell Counting Kit-8. The levels of LDH, MDA, SOD, TNF-α, IL-6 levels were detected using their respective ELISA kits. In addition, the levels of Nrf2 and P-gp protein expression were detected by western blot analysis. The concentration of PQ was measured by HPLC. The results revealed that overexpressed Nrf2 significantly increased P-gp protein levels, decreased the intracellular accumulation of PQ and attenuated PQ-induced toxicity. However, the protective effects of Nrf2 overexpression on PQ-challenged A549 cells were abrogated following cyclosporine A treatment, a competitive inhibitor of P-gp, which also increased intracellular PQ levels. These data indicated that Nrf2 gene overexpression prevented PQ toxicity in A549 cells, potentially via the upregulation of P-gp activity and the inhibition of intracellular PQ accumulation. Thus, Nrf2 and P-gp may serve as potential therapeutic targets for the treatment of PQ-induced injury.

Paraquat (PQ) is a heterocyclic pesticide that not only damages the testicular development and reduces the quality of semen, but also disturbs the secretion of hormones in the reproductive system. However, the effects of PQ on oocyte maturation and its toxic mechanism have not been yet fully clarified. Here we showed that PQ exposure could have toxic effects on porcine oocyte maturation. PQ exposure with 100 μM inhibited cumulus cell expansion and significantly reduced the rate of first polar body extrusion during oocyte maturation. PQ-exposed oocytes could not develop to the 2-cell and blastocyst stage. PQ exposure with 100 μM significantly increased abnormal spindle rate (65.2% ± 1.0%) and misaligned chromosome rate (63.2% ± 3.4%) compared to the control group (38.3% ± 1.0% and 38.4% ± 1.0%, respectively; P < 0.05). F-actin also exhibited reduced distribution in PQ-exposed oocytes (10.3% ± 1.0%) compared to the control group (14.4% ± 1.0%, P < 0.05). In addition, PQ exposure reduced the active mitochondria levels, but apparently increased the reactive oxygen species (ROS), rH2AX, and LC3 (autophagy marker) levels. qPCR analyses showed that PQ exposure caused the aberrant expression of genes associated with cumulus cell expansion, but did not affect the expression of apoptosis-related genes. Taken together, these results indicate that PQ exposure impaired oocyte nuclear and cytoplasmic maturation probably through oxidative stress.

In this study, we investigated the effects of one-off applications of glyphosate, glufosinate, paraquat, and paraquat-diquat on soil microbial diversity and function. All herbicides were added to soil as pure compounds at recommended dose and were incubated under laboratory conditions for 60 days. High-throughput phylogenetic marker gene sequencing revealed that none of the herbicides significantly influenced the richness, evenness and composition of bacterial and archaeal communities. Likewise, the diversity, composition and size of nematode communities were not significantly influenced by any of the herbicides. From a functional perspective, herbicides did not significantly affect fluorescein diacetate hydrolysis (FDA) and beta-glucosidase activities. Furthermore, the ability of soil organisms to utilise 15 substrates was generally unaffected by herbicide application. The only exception to this was a temporary impairment in the ability of soil organisms to utilise three organic acids and an amino acid. Given the global and frequent use of these herbicides, it is important that future studies evaluate their potential impacts on microbial communities in a wider-range of soils and environmental conditions.

Herbicides containing paraquat may contribute to the pathogenesis of neurodegenerative disorders such as Parkinson's disease. Paraquat induces reactive oxygen species-mediated apoptosis in neurons, which is a primary mechanism behind its toxicity. We sought to test the effectiveness of a commercially available polyphenol-rich Aronia melanocarpa (aronia berry) concentrate in the amelioration of paraquat-induced neurotoxicity. Considering the abundance of antioxidants in aronia berries, we hypothesized that aronia berry concentrate attenuates the paraquat-induced increase in reactive oxygen species and protects against paraquat-mediated neuronal cell death. Using a neuronal cell culture model, we observed that low doses of aronia berry concentrate protected against paraquat-mediated neurotoxicity. Additionally, low doses of the concentrate attenuated the paraquat-induced increase in superoxide, hydrogen peroxide, and oxidized glutathione levels. Interestingly, high doses of aronia berry concentrate increased neuronal superoxide levels independent of paraquat, while at the same time decreasing hydrogen peroxide. Moreover, high-dose aronia berry concentrate potentiated paraquat-induced superoxide production and neuronal cell death. In summary, aronia berry concentrate at low doses restores the homeostatic redox environment of neurons treated with paraquat, while high doses exacerbate the imbalance leading to further cell death. Our findings support that moderate levels of aronia berry concentrate may prevent reactive oxygen species-mediated neurotoxicity.

The biodegradation of paraquat was investigated using immobilized microbial cells on nanoceramics fabricated from nanoscale kaolinite. Pseudomonas putida and Bacillus subtilis, which degrade paraquat, were immobilized separately on nanoceramics (respectively called ICnc-P and ICnc-B). The attachment of bacteria to nanoceramics resulted from electrostatic force interactions, hydrogen bonding, and covalent bonding (between the cells and the support materials). The initial 10 mg L-1 concentration of paraquat in water was removed by the adsorption process using nanoceramics at 68% and ceramics at 52%, respectively. The immobilized cells on the nanoceramics were able to remove approximately 92% of the paraquat within 10 h, whereas the free cells could only remove 4%. When the paraquat was removed, the cell-immobilized nanoceramics exhibited a significant decrease in dissolved organic nitrogen (DON). ICnc-B was responsible for 34% of DON biodegradation, while ICnc-P was responsible for 22%. Ammonia was identified as the end product of ammonification resulting from paraquat mineralization.

Paraquat (PQ) has been implicated as a risk factor for the Parkinson disease phenotype (PDP) in humans and mice using epidemiologic or experimental approaches. The toxicokinetics (TK) and toxicodynamics (TD) of PQ in the brain are not well understood.

Paraquat (PQ) is a non-selective herbicide and is exceedingly toxic to humans. The mechanism of PQ toxicity is very complex and has not been clearly defined. There is no specific antidote for PQ poisoning. 5-hydroxy-1-methylhydantoin (HMH) is an intrinsic antioxidant and can protect against renal damage caused by PQ. The mechanism of PQ toxicology and the possible effects of HMH on PQ-induced lung injury were determined in this study. It was found that PQ decreased superoxide dismutase (SOD) activity and elevated the level of malondialdehyde (MDA), while HMH elevated SOD activity and decreased the level of MDA. Based on metabolomics, the citrate cycle, glutathione metabolism, taurine and hypotaurine metabolism, regulation of lipolysis in adipocytes, inflammatory mediator regulation of TRP channels, purine and pyrimidine metabolism, aldosterone synthesis and secretion, and phenylalanine metabolism were changed in the PQ group. Compared with the PQ group, the levels of N-acetyl-l-aspartic acid, L-glutamic acid, L-aspartic acid, mesaconic acid, adenosine 5' monophosphate, methylmalonic acid, cytidine, phosphonoacetic acid, hypotaurine, glutathione (reduced) and cysteinylglycine increased, while the levels of corticosterone, xanthine, citric acid, prostaglandin G2, 4-pyridoxic acid and succinyl proline decreased in the HMH group. These metabolites revealed that HMH can alleviate inflammation caused by PQ and elevate the activity of intrinsic antioxidants. In conclusion, our results revealed PQ toxicology and the pharmacology underlying the protective effect of HMH on lung injury due to PQ. Toxicity caused by PQ results in lipid peroxidation and an increase in reactive oxygen species (ROS), nitric oxide (NO), damage to the biliary system, gastrointestinal system and nervous system, in addition to lungs, kidneys, and the liver. HMH is a good antioxidant and protects against lung injury caused by PQ. In summary, HMH efficiently reduced PQ-induced lung injury in mice.

To conduct a kinetic study of paraquat (PQ), we investigated 9 patients with acute PQ intoxication. All of them ingested more than 20 ml of undiluted PQ herbicide to commit suicide and arrived at our hospital early, not later than 7 h after PQ ingestion. The urine dithionite test for PQ in all of the nine patients was strongly positive at emergency room. Blood samples were obtained every 30 min for the first 2~3 h and then every 1 or 2 h, as long as the clinical progression was stable among the patients for 30 h after PQ ingestion. The area under the plasma concentration-time curve (AUCinf), which was extrapolated to infinity, was calculated using the trapezoidal rule. Toxicokinetic parameters, such as the terminal elimination half-life, apparent oral clearance, and apparent volume of distribution (Vd/F) were calculated. The maximum PQ concentration (Cmax) and the time to reach maximum PQ concentration (Tmax) were also obtained. Plasma PQ concentrations in nine patients were well described by a bi-exponential curve with a mean terminal elimination half-life of 13.1±6.8 h. Cmax and AUCinf were 20.8±25.7 mg/l and 172.5±160.3 h·mg/l, respectively. Apparent volume of distribution and apparent oral clearance were 50.9±61.3 l/kg and 173.4±111.2 l/h, respectively. There were a significant correlation (r =0.84; p<0.05) between the PQ amount ingested and Cmax. AUCinf also showed a significant correlation (r =0.83; p<0.05) with the PQ amount ingested. These correlations provide evidence that PQ has dose-linear toxicokinetic characteristics.

Paraquat (PQ), a widely used environmental toxin in agriculture, contributes to the onset and progression of Parkinson's disease (PD) by damaging neurons. The JWA gene, also known as ARL6IP5, exerts a protective effect on degenerating dopamine (DA) neurons. However, the roles of JWA in PQ-induced neuronal damage are still unknown. In our study, two neuronal cell lines (HT-22 and SH-SY5Y) and neuron-specific JWA knockout (JWA-nKO) and age-matched wild-type (JWA-nWT) mice were subjected to PQ treatment. The results indicate that PQ administration triggers the upregulation of JWA. Elevated expression of JWA rescues the accumulation of reactive oxygen species (ROS) while increasing glutathione (GSH) and glutathione peroxidase (GPx) levels under PQ exposure. Further investigations revealed that the protective effect of JWA mostly involves regulation of the MEK/PI3K-Nrf2 axis. Our results suggest that JWA may be a novel target for the prevention and treatment of PQ-induced PD.

Paraquat (PQ) is a potential human neurotoxicant and is used in models of oxidative stress. We determined the toxicokinetics (TK) and toxicodynamics (TD) of PQ in adult mouse brain following repeated or prolonged PQ exposure. PQ accumulated in different brain regions and reached a plateau after approximately 18 i.p. (10 mg/kg) doses and resulted in modest morbidity and mortality unpredictably associated with dose interval and number. PQ had divergent effects on horizontal locomotor behavior depending on the number of doses. PQ decreased striatal dopamine levels after the 18th to 36th i.p. dose (10 mg/kg) and reduced the striatal level of tyrosine hydroxylase. Drinking water exposure to PQ (0.03- 0.05 mg/ml) did not result in any mortality and resulted in concentration and time dependent levels in the brain. The brain half-life of PQ varied with mouse strain. PQ accumulates and may saturate a site in mouse brain resulting in complex PQ level and duration-related consequences. These findings should alter our risk assessment of this compound and demonstrate a useful, but complex dynamic model for understanding the consequences of PQ in the brain.

Paraquat (PQ) has been demonstrated that the main target organ for the toxicity is the lung. This study aimed to investigate the potential protective effect of PDTC on the PQ-induced pulmonary damage. Fifty-four rats were divided into control, PQ-treated and PQ+PDTC-treated groups. Rats in the PQ group were administrated 40 mg/kg PQ by gastric gavage, and PDTC group with 40 mg/kg PQ followed by injection of 120 mg/kg PDTC (IP). On the days 3, 7, 14 and 21 after treatments, the activities of GSH-Px, SOD, MDA level and the content of HYP were measured. TGF-beta1 mRNA and protein were assayed by RT-PCR and ELISA. MDA level in plasma and BALF was increased and the activities of GSH-Px and SOD were decreased significantly in the PQ-treated groups (P < .05) compared with control group. While the activities of GSH-Px and SOD in the PQ+PDTC-treated groups was markedly higher than that of PQ-treated groups (P < .05), and in contrast, MDA level was lower. TGF-beta1 mRNA and protein were significantly lower in the PQ+PDTC-treated groups than that of PQ-treated groups (P < .05). The histopathological changes in the PQ+PDTC-treated groups were milder than those of PQ groups. Our results suggested that PDTC treatment significantly attenuated paraquat-induced pulmonary damage.

Triadimefon (TDF), a triazole fungicide, and paraquat (PQ), a non-selective herbicide/dessicant, are both known to adversely impact brain dopaminergic function and are used in overlapping geographical areas of the US. Since "real world" situations indicate humans are exposed to a diverse mixture of chemicals, this study hypothesized that combined exposures to PQ+TDF could produce interactive effects by simultaneously attacking multiple target sites of dopamine systems. Thus, 10 mg/kg PQ (PQ10) and 25 or 50 mg/kg TDF (TDF25 and 50, respectively) were administered i.p. to male C57BL/6 mice, 2x per week for 12 weeks, either alone or in combination. Acutely, TDF50 increased horizontal and vertical activity with increased vertical activity still occurring 24h later, indicative of sustained behavioral sensitization. Acutely, PQ decreased horizontal but not vertical activity with a lack of residual effects at 24h. PQ prevented the increased levels of activity associated with TDF50. These interactions differed for horizontal and vertical activity, indicating their differential neurochemical mediation, and suggesting that they did not arise from simple additivity of PQ and TDF effects. Nor could the interactive effects be readily ascribed to corresponding neurochemical interactions, since all treatments generally increased levels of DA and metabolites acutely in striatum and were associated with general reductions in levels of DA and metabolites and turnover in striatum and frontal cortex 7 days after the final treatment. Thus, TDF and PQ both separately and through interactions may serve as environmental risk factors through different mechanisms for dopaminergically-mediated behavioral dysfunctions.

Paraquat (PQ) concentration-time data have been used to predict prognosis for 3 decades. The aim of this study was to find a more accurate method to predict the probability of survival.

Paraquat (PQ) is a highly lethal herbicide. Ingestion of large quantities of PQ usually results in cardiovascular collapse and eventual mortality. Recent pieces of evidence indicate possible involvement of oxidative stress- and inflammation-related factors in PQ-induced cardiac toxicity. However, little information exists on the relationship between hemodynamic and cardiac electromechanical effects involved in acute PQ poisoning. The present study investigated the effects of acute PQ exposure on hemodynamics and electrocardiogram (ECG) in vivo, left ventricular (LV) pressure in isolated hearts, as well as contractile and intracellular Ca2+ properties and ionic currents in ventricular myocytes in a rat model. In anesthetized rats, intravenous PQ administration (100 or 180 mg/kg) induced dose-dependent decreases in heart rate, blood pressure, and cardiac contractility (LV +dP/dtmax). Furthermore, PQ administration prolonged the PR, QRS, QT, and rate-corrected QT (QTc) intervals. In Langendorff-perfused isolated hearts, PQ (33 or 60 μM) decreased LV pressure and contractility (LV +dP/dtmax). PQ (10-60 μM) reduced the amplitudes of Ca2+ transients and fractional cell shortening in a concentration-dependent manner in isolated ventricular myocytes. Moreover, whole-cell patch-clamp experiments demonstrated that PQ decreased the current amplitude and availability of the transient outward K+ channel (Ito) and altered its gating kinetics. These results suggest that PQ-induced cardiotoxicity results mainly from diminished Ca2+ transients and inhibited K+ channels in cardiomyocytes, which lead to LV contractile force suppression and QTc interval prolongation. These findings should provide novel cues to understand PQ-induced cardiac suppression and electrical disturbances and may aid in the development of new treatment modalities.

Paraquat has been suggested to induce apoptosis by generation of reactive oxygen species (ROS). However, little is known about the mechanism of paraquat-induced apoptosis. Here, we demonstrate that extracellular signal-regulated protein kinase (ERK) is required for paraquat-induced apoptosis in NIH3T3 cells. Paraquat treatment resulted in activation of ERK, and U0126, inhibitors of the MEK/ERK signaling pathway, prevented apoptosis. Moreover, paraquat-induced apoptosis was associated with cytochrome C release, which could be prevented by treatment with the MEK inhibitors. Taken together, our findings suggest that ERK activation plays an active role in mediating paraquat-induced apoptosis of NIH3T3 cells.