Paraquat Treatment Research Articles

Sexual dysfunction precedes motor defects, dopaminergic neuronal degeneration, and impaired dopamine metabolism: Insights from Drosophila model of Parkinson's disease.

Sexual dysfunction (SD) is one of the most common non-motor symptoms of Parkinson's disease (PD) and remains the most neglected, under-reported, and under-recognized aspect of PD. Studies have shown that Dopamine (DA) in the hypothalamus plays a role in regulating sexual behavior. But the detailed mechanism of SD in PD is not known. Drosophila melanogaster shares several genes and signaling pathways with humans which makes it an ideal model for the study of a neurodegenerative disorder such as PD. Courtship behavior of Drosophila is one such behavior that is closely related to human sexual behavior and so plays an important role in understanding sexual behavior in diseased conditions as well. In the present study, a sporadic SD model of PD using Drosophila was developed and SD phenotype was observed based on abnormalities in courtship behavior markers. The Drosophila SD model was developed in such a way that at the window of neurotoxin paraquat (PQ) treatment [PQ is considered a crucial risk factor for PD due to its structural similarity with 1-methyl-4-phenyl pyridinium (MPP+), the active form of PD-inducing agent, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)], it does not exhibit mobility defects but shows SD. The whole brain tyrosine hydroxylase immunostaining showed no observable dopaminergic (DAergic) degeneration (number of DA neurons and fluorescence intensity of fluorescently labeled secondary antibodies that target anti-TH primary antibody) of the SD model. Similarly, there was no significant depletion of brain DA and its metabolite levels (HVA and DOPAC) as determined using HPLC-ECD (High-Performance Liquid Chromatography using Electrochemical Detector). The present study illustrates that the traits associated with courtship and sexual activity provide sensitive markers at the earlier stage of PD onset. This PQ-induced SD fly model throws an opportunity to decipher the molecular basis of SD under PD conditions and to screen nutraceuticals/potential therapeutic molecules to rescue SD phenotype and further to DAergic neuroprotection.

High-Nitrate-Supply-Induced Transcriptional Upregulation of Ascorbic Acid Biosynthetic and Recycling Pathways in Cucumber

Nowadays open field and protected vegetable cultivation practices require and use genotypes which are precisely tailored to their intended growth environments. Variability of this kind provides a rich source of material to uncover molecular mechanisms supporting the necessarily divergent physiological traits. In this study, typical field-optimized and glasshouse-cultivated cucumber F1 hybrids were investigated, and displayed slower growth ('Joker') and faster growth ('Oitol') in seedlings. Antioxidant capacity was lower in 'Joker' and higher in 'Oitol', pointing to a potential redox regulation of growth. The growth response of seedlings to paraquat treatment indicated stronger oxidative stress tolerance in the fast-growing 'Oitol'. To test whether protection against nitrate-induced oxidative stress was also different, fertigation with increasing potassium nitrate content was applied. This treatment did not change growth but decreased the antioxidant capacities of both hybrids. Bioluminescence emission revealed stronger lipid peroxidation triggered by high nitrate fertigation in the leaves of 'Joker' seedlings. To explore the background of the more effective antioxidant protection of 'Oitol', levels of ascorbic acid (AsA), as well as transcriptional regulation of relevant genes of the Smirnoff-Wheeler biosynthetic pathway and ascorbate recycling, were investigated. Genes related to AsA biosynthesis were strongly upregulated at an elevated nitrate supply in 'Oitol' leaves only, but this was only reflected in a small increase in total AsA content. High nitrate provision also triggered expression of ascorbate-glutathion cycle genes with stronger or exclusive induction in 'Oitol'. AsA/dehydro-ascorbate ratios were higher in 'Oitol' for all treatments, with a more pronounced difference at high nitrate levels. Despite strong transcriptional upregulation of ascorbate peroxidase genes (APX) in 'Oitol', APX activity only increased significantly in 'Joker'. This suggests potential inhibition of APX enzyme activity specifically in 'Oitol' at a high nitrate supply. Our results uncover an unexpected variability in redox stress management in cucumbers, including nitrate inducibility of AsA biosynthetic and recycling pathways in certain genotypes. Possible connections between AsA biosynthesis, recycling and nitro-oxidative stress protection are discussed. Cucumber hybrids emerge as an excellent model system for studying the regulation of AsA metabolism and the roles of AsA in growth and stress tolerance.

Therapeutic potential of amitriptyline for paraquat-induced pulmonary fibrosis: Involvement of caveolin-1-mediated anti-epithelial-mesenchymal transition and inhibition of apoptosis

ObjectiveTreatment of pulmonary fibrosis caused by paraquat (PQ) poisoning remains problematic. Amitriptyline (AMT) has multiple pharmacological effects. Here we investigated the anti-fibrotic effect of AMT on PQ-induced pulmonary fibrosis and its possible mechanism. MethodsC57BL/6 mice were randomly divided into control, PQ, PQ + AMT and AMT groups. Histopathology of the lungs, blood gas analysis, and levels of hydroxyproline (HYP), transforming growth factor β1 (TGF-β1) and interleukin 17 (IL-17) were measured. The siRNA transfection inhibited caveolin-1 in A549 cells, which induced epithelial-mesenchymal transition (EMT) by PQ and followed intervention with AMT. E-cadherin, N-cadherin, α-smooth muscle actin (α-SMA) and caveolin-1 were studied by immunohistochemistry and western blot analysis. The apoptosis rate was measured by flow cytometry. ResultsCompared with the PQ group, the PQ + AMT group displayed mild pathological changes in pulmonary fibrosis, lower HYP, IL-17 and TGF- β1 levels in lung, but high TGF- β1 in serum. Levels of N-cadherin and α-SMA in the lungs were significantly decreased, but caveolin-1 was increased, while SaO2 and PaO2 levels were higher. Compared with the PQ group, the apoptosis rate, N-cadherin and α-SMA levels in A549 cells were significantly decreased after PQ treatment and high dose AMT intervention (p < 0.01). The expressions of E-cadherin, N-cadherin and α-SMA in the PQ-induced cells transfected with caveolin-1 siRNA or siControl RNA were significantly different (p < 0.01), but the apoptosis rate was unaltered. ConclusionAMT inhibited PQ-induced EMT in A549 cells and improved lung histopathology and oxygenation in mice by up-regulating caveolin-1.

Assessing Short-Term Vitamin E and C Treatment Effect in Paraquat Liver Poisoning

Paraquat has been considered as a toxicant in various countries, since it is not only intensely harmful but yet promptly accessible and generally cheap. Vitamin C and E are notable cancer prevention agents that respond rapidly to free radical and maximally forestall lipid peroxidation. The aim of this study was to evaluate the ameliorative impact of vitamin E and C in paraquat induced liver poisoning in rat. A total of 200 male wistar rats were obtained for the study. With 50 rats each, the rats were arranged into four grougs: A, B, C, and D. Each group was partitioned into two subgroups (0 and VEC), each with 25 rodents. The "A" group was not treated with paraquat, while the "B," "C," and "D" groups got 0.02g, 0.04g, and 0.06g of paraquat treatment respectively. All the "0" subgroups were those not treated with Vit E and C and all “VEC” subgroups were those treated with 500mg of vitamin E and 2000mg/dl of vitamin C. The paraquat treatment was administered once every 2 weeks for 3 months, followed by one month of week by week vitamin E and C treatment. Blood was drawn for SGPT, SGOT, ALP, and GGT testing. At p-value of 0.05, there was a significant increase in the activities of liver enzymes among the "A0", "B0", "C0", and "D0" groups. There was a significant decrease (P-value&lt;0.05) in the activities of liver enzymes in “VEC” subgroups. This study uncovered that vitamin E and C combined treatment ameliorated the Paraquat induced liver injury in rats.

Ameliorative Effect of Vitamin E on Paraquat Induced Nephrotoxicity in Rat

The kidney is a very vital organ required for excretion of metabolic waste products in the body and when the kidney is damaged, this function is compromised. Paraquat is a toxicant that is known to have toxic injuries in different organs. Therefore, the aim of this study was to uncover the treatment effect of vitamin E in paraquat inflicted kidney injury. The experimental animals (male rats) were 200 and they were classified into 4 groups designated as A, B, C and D. The A served as the control group, B, C and D were test groups classified based on dose of paraquat administered. A was not treated with paraquat, B, C and D were treated with 0.02g, 0.04g and 0.06g of paraquat respectively every two weeks for three months. Each group mentioned had subgroups designated “0” and “VE”; “0” subgroups were subgroups not treated with vitamin E while “VE” were subgroups treated with 500mg of vitamin E. Treatment of vitamin E occurred weekly for one month. Both vitamin E and paraquat treatments occurred orally. After treatment period rats were sacrificed and blood sample collected via cardiac puncture for urea and creatinine assay. The results showed that there was no significant difference in urea levels among paraquat alone treated groups but there was a significant increase in creatinine levels among paraquat alone treated groups. There was a significant decrease in creatinine level after vitamin E treatment. This study has shown that vitamin E is a therapeutic hope for paraquat inflicted nephrotoxicity in rats.

Ameliorative Effect of Vitamin E and C on Paraquat Induced Nephrotoxicity in Rat

The kidney is an exceptionally essential organ required for metabolic byproducts elimination in the body and when the kidney is impaired, this role is compromised. Paraquat is a poison that is known to have harmful effect in various organs. Subsequently, the point of this study was to reveal the treatment impact of vitamin E and C in paraquat poisoned kidney in rat. The rat were 200 and they were classified into 4 groups assigned as A, B, C and D. The A group was the control, B, C and D were test groups classified in light of dose of paraquat given. “A” was not treated with paraquat, B, C and D were treated with 0.02g, 0.04g and 0.06g of paraquat separately at regular intervals of 2 weeks for 3 months. Each group had subgroups assigned "0" and "VEC"; "0" subgroups were subgroups not treated with vitamin E while "VEC" were subgroups treated with 500mg of vitamin E and 2000mg/dl vitamin C. Treatment of vitamin E and C happened week after week for one month. Both vitamins and paraquat treatment happened orally. After treatment period, the rats were sacrificed and blood sample collected through cardiac puncture for urea and creatinine assay. The outcomes showed that there was no significant difference in urea levels among only paraquat treated groups yet there was a significant increase in creatinine levels among only paraquat treatment groups. There was a significant decrease in creatinine level after vitamin E and C treatment. This study has shown that vitamin E and C is capable of restoring kidney function paraquat induced nephrotoxicity in rat.

Paraquat and Diquat: Recent Updates on Their Pretreatment and Analysis Methods since 2010 in Biological Samples.

Paraquat (PQ) and diquat (DQ) are quaternary ammonium herbicides which have been used worldwide for controlling the growth of weeds on land and in water. However, PQ and DQ are well known to be toxic. PQ is especially toxic to humans. Moreover, there is no specific antidote for PQ poisoning. The main treatment for PQ poisoning is hemoperfusion to reduce the PQ concentration in blood. Therefore, it is essential to be able to detect PQ and DQ concentrations in biological samples. This critical review summarizes the articles published from 2010 to 2022 and can help researchers to understand the development of the sample treatment and analytical methods for the determination of PQ and DQ in various types of biological samples. The sample preparation includes liquid-liquid extraction, solid-phase extraction based on different novel materials, microextration methods, and other methods. Analytical methods for quantifying PQ and DQ, such as different chromatography and spectroscopy methods, electrochemical methods, and immunological methods, are illustrated and compared. We focus on the latest advances in PQ and DQ treatment and the application of new technologies for these analyses. In our opinion, tandem mass spectrometry is a good choice for the determination of PQ and DQ, due to its high sensitivity, high selectivity, and high accuracy. As far as we are concerned, the best LOD of 4 pg/mL for PQ in serum can be obtained.

The role of the antioxidant system and the photosynthetic behavior of paraquat-resistant Conyza sumatrensis in Brazil

Greenhouse experiments were carried out aiming to characterize—morphologically and biochemically—resistant and susceptible plants of C. sumatrensis. Two experiments were carried out to evaluate the behavior of morphological variables such as leaf area, height, and dry biomass weight, without application of paraquat (1,1'-dimethyl-4,4'-bipyridinium dichloride). Other experiments were conducted with two rates of paraquat application (0 and 800 g a.i ha−1); physiological variables were assessed at 2, 4, and 24 h after application (HAA), and plants were collected at 4 HAA for biochemical analyses of antioxidant enzymes and cell membrane peroxidation level. Without herbicide application, paraquat-resistant populations had higher dry biomass, leaf area, liquid photosynthetic rate, carboxylation efficiency, and stomatal conductance. The recovery of the photosynthetic apparatus by resistant plants after paraquat application is rapid (16 HAA) and, in general, presents physiological improvements in terms of photosynthetic rate and carboxylation efficiency. After paraquat treatment, the antioxidant system enzymes of resistant plants showed increased activity and decreased membrane peroxidation, indicating that these enzymes play an important role in the resistance mechanism of these plants.

Frpr-18, a neuropeptide receptor, regulates organismal lifespan and stress tolerance in C. elegans.

The mechanisms underlying neuropeptide signaling regulation of lifespan in Caenorhabditis elegans ( C. elegans ) remain unclear. FRPR-18 is a mammalian orexin/hypocretin-like receptor and modulates C. elegans arousal behavior by acting as a receptor for FLP-2 neuropeptide signaling, which is also associated with the systemic activation of the mitochondrial unfolded protein response (mitoUPR). Here we report our preliminary findings on the role of the frpr-18 gene in regulating lifespan and healthspan parameters, including stress resistance. Our results showed that frpr-18(ok2698) null mutants had a shorter lifespan and reduced survivability against thermal stress and paraquat treatment. On the other hand, loss of flp-2 function did not affect lifespan or paraquat tolerance but was necessary for normal thermal stress tolerance. These findings suggest that frpr-18 could play a role in regulating lifespan and stress resistance, possibly through flp-2 independent or parallel neuropeptide signaling pathways.

Investigating the Efficacy of Sucralfate in the Treatment of Oral Paraquat Poisoning: A Randomized Double-Blind Clinical Trial

Background: There is a high prevalence of intentional paraquat poisoning especially for suicide reported from many part of the world, with its negative effects on the lungs, kidneys, heart, and digestive system. This study was planned, aimed at investigating the efficacy of sucralfate in the treatment of oral paraquat poisoning with respect to its clinical outcomes. Methods: A randomized double-blind clinical trial was conducted on 70 patients, suffering from oral paraquat poisoning. These patients were divided into two groups of 35 each. Subsequently, gastric lavage was performed for each patient in the control and treatment groups with 5g sucralfate mixed in tap water in the treatment group, but with tap water alone in the controls. The patients’ hemodynamic and laboratory parameters were evaluated and recorded, on admission and the hospital discharge dates. In addition, the patients’ final clinical outcome, including survival or death was also recorded. Results: The results of the present study revealed that the patients’ hemodynamic parameters, coagulation factors, renal and liver laboratory findings did not differ significantly between the two groups (P&gt;0.05). Moreover, 45.7% and 31.4% of the patients died in the control and treatment groups, respectively (P&gt;0.05). Conclusions: The sucralfate administration did not have a significant effect on the patients’ hemodynamic and laboratory parameters. The survival of patients in the treatment group was slightly higher than those in the control group. Also the patients in the treatment group had less pulmonary and renal complications in the long-term than those in the control group.

AdoR-1 (Adenosine Receptor) Contributes to Protection against Paraquat-Induced Oxidative Stress in Caenorhabditis elegans.

AdoR-1, the single adenosine receptor homolog in Caenorhabditis elegans, which belongs to the superfamily of G-protein coupled receptors (GPCRs), mediates most of the physiological effects of extracellular adenosine. Adenosine has been proved to improve the survival rate of C. elegans in oxidative stress conditions. However, the potential mechanism of adenosine's protective effect against oxidative stress via AdoR-1 has not been studied. In this study, C. elegans were divided into three groups: two groups with paraquat treatment, one in the presence and one in the absence of adenosine, and an untreated control group. Results indicate that many differentially expressed genes were found to be enriched significantly in neural-related signaling pathways among transcriptome data of three groups. Further gene network analysis showed that some important genes well known to be involved in promoting the acetylcholine release pathway, such as dop-1, egl-30, and unc-13, and those involved in promoting the neuropeptide release pathway, such as kin-1, were upregulated by paraquat induction but downregulated after adenosine treatment. Meanwhile, a completely opposite trend was observed for the goa-1 gene that inhibits the acetylcholine-release and neuropeptide-release pathway. Additionally, some biochemical assays including SOD, GSSG, GSH, and AChE were measured to identify the potential protection of adenosine against oxidative stress between wild-type strain N2 and ador-1 gene knockout strain EG6890. Conclusively, our study revealed series of adenosine receptor-mediated genes in C. elegans that might act as regulators of paraquat-induced oxidative stress and may indicate adenosine's promising protective effects.

Insulin Signaling Disruption and INF-γ Upregulation Induce Aβ1-42 and Hyperphosphorylated-Tau Proteins Synthesis and Cell Death after Paraquat Treatment of Primary Hippocampal Cells.

Acute and long-term paraquat (PQ) exposure produces hippocampal neurodegeneration and cognition decline. Although some mechanisms involved in these effects were found, the rest are unknown. PQ treatment, for 1 and 14 days, upregulated interferon-gamma signaling, which reduced insulin levels and downregulated the insulin pathway through phosphorylated-c-Jun N-terminal-kinase upregulation, increasing glucose levels and the production of Aβ1-42 and phosphorylated-tau, by beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) overexpression and phosphorylated-GSK3β (p-GSK3β; ser9) level reduction, respectively, which induced primary hippocampal neuronal loss. This novel information on the PQ mechanisms leading to hippocampal neurodegeneration could help reveal the PQ actions that lead to cognition dysfunction.

Paraquat induces apoptosis, programmed necrosis, and immune dysfunction in CIK cells via the PTEN/PI3K/AKT axis

Paraquat (PQ) is a highly water-soluble, non-selective herbicide. Due to water pollution and lack of specific medicines, it is extremely harmful to humans and aquatic animals. Oxidative stress and apoptosis can affect the immune function of the body. However, the effects and mechanisms of PQ on the immune function, apoptosis and programmed necrosis on CIK cells are still unclear. Therefore, we constructed low (L, 50 μmol/L), medium (M, 100 μmol/L), and high (H, 150 μmol/L) dose models of PQ exposure on CIK cells. The expression of oxidative stress-related indexes (MDA, CAT, GSH-Px and SOD) and interrelated genes were examined by flow cytometry, qRT-PCR, and western blotting methods. Our data demonstrated that PQ treatment caused an increase in MDA content and the decreases in the activities of antioxidase and antioxidants (SOD, GSH-Px and CAT) on CIK cells (p < 0.05). We also discovered the PTEN/PI3K/AKT pathway was significantly activated in a dose dependent manner (p < 0.05). Furthermore, the proportion of programmed necrosis cells increased dramatically at PQ doses from 0 μmol/L to 150 μmol/L. Apoptosis and necrosis-related genes also showed dose-dependent changes (p < 0.05). Briefly, PQ exposure leads to apoptosis and programmed necrosis via the oxidative stress and PTEN/PI3K/AKT pathway, thereby causing immune dysfunction of CIK cells. This study enriches the toxic influences of PQ on the cells of aquatic organisms and provides a reference for comparative medicine.

Plasma treatment effects on destruction and recovery of Porphyromonas gingivalis biofilms.

The objective of this study was to investigate the treatment effects of non-thermal atmospheric gas plasmas (NTAP) on destruction and the recovery (or re-colonization) of Porphyromonas gingivalis (P. gingivalis) in biofilms. P. gingivalis is a well-known keystone periodontal pathogen strongly associated with periodontal diseases, especially periodontitis. P. gingivalis biofilms were formed on stainless steel coupons and treated for 1, 2, and 5 minutes by NTAP of pure argon gas and argon+oxygen gas mixture. MTT assay, colony forming unit (CFU) counting assay and confocal laser scanning microscopy (CLSM) were used to assess the destruction efficiency. In addition, the plasma treated biofilms were re-cultured in the medium supplemented with antibiotics and oxidative stress sources to determine the synergy of the NTAP with other antimicrobial agents. The results showed the plasma treatment could result in 2.7 log unit reduction in bacterial load. The recovered biofilm CFU with NTAP treatment combined with sub minimal inhibition concentration of amoxicillin was 0.33 log units less than the biofilm treated with amoxicillin alone. The recovered biofilm CFU in NTAP groups was about 2.0 log units less than that in the untreated controls under H2O2 treatment. There was approximately 1.0 log unit reduction of biofilm CFU in plasma treated biofilm compared with untreated control under paraquat treatment. The plasma treated biofilms exhibited less resistance to amoxicillin and greater susceptibility to hydrogen peroxide (H2O2) and paraquat, suggesting that NTAP may enhance biofilm susceptibility to host defense. These in vitro findings suggested that NTAP could be a novel and effective treatment method of oral biofilms that cause periodontal diseases.

Potential Mechanisms Involved in Chronic Kidney Disease of Unclear Etiology.

The etiology of chronic kidney disease of unclear etiology, also known as Mesoamerican nephropathy, remains unclear. We investigated potential etiologies for Mesoamerican nephropathy in an immigrant dialysis population. Migrants with Mesoamerican nephropathy kidney failure (n=52) were identified by exclusion of known causes of kidney disease and compared using a cross-sectional survey with demographically similar patients with kidney failure from other causes (n=63) and age/sex/place of origin-matched healthy participants (n=16). Survey results were extended to the bench; C57BL/6 mice (n=73) received 10-15 weekly intraperitoneal injections of paraquat (a reactive oxygen species-generating herbicide) or vehicle. Kidney function, histology, and expression of organic cation transporter-2 (proximal tubule entry for paraquat) and multidrug and toxin extrusion 1 (extrusion pathway) were examined. Kidney biopsies from Nicaraguan patients with acute Mesoamerican nephropathy were stained for the above transporters and compared with patients with tubulointerstitial nephritis and without Mesoamerican nephropathy. Patients with Mesoamerican nephropathy and kidney failure were young agricultural workers, almost exclusively men; the majority were from Mexico and El Salvador; and they had prior exposures to agrochemicals, including paraquat (27%). After adjustment for age/sex, exposure to any agrochemical or paraquat was associated with Mesoamerican nephropathy kidney failure (odds ratio, 4.86; 95% confidence interval, 1.82 to 12.96; P=0.002 and odds ratio, 12.25; 95% confidence interval, 1.51 to 99.36; P=0.02, respectively). Adjusted for age/sex and other covariates, 1 year of agrochemical exposure was associated with Mesoamerican nephropathy kidney failure (odds ratio, 1.23; 95% confidence interval, 1.04 to 1.44; P=0.02). Compared with 16 matched healthy controls, Mesoamerican nephropathy kidney failure was significantly associated with exposure to paraquat and agrochemicals. Paraquat-treated male mice developed kidney failure and tubulointerstitial nephritis consistent with Mesoamerican nephropathy. Organic cation transporter-2 expression was higher in male kidneys versus female kidneys. Paraquat treatment increased organic cation transporter-2 expression and decreased multidrug and toxin extrusion 1 expression in male kidneys; similar results were observed in the kidneys of Nicaraguan patients with Mesoamerican nephropathy. Exposure to agrochemicals is associated with Mesoamerican nephropathy, and chronic exposure of mice to paraquat, a prototypical oxidant, induced kidney failure similar to Mesoamerican nephropathy.

Phenotypic analyses, protein localization, and bacteriostatic activity of Drosophila melanogaster transferrin-1

Transferrin-1 (Tsf1) is an extracellular insect protein with a high affinity for iron. The functions of Tsf1 are still poorly understood; however, Drosophila melanogaster Tsf1 has been shown to influence iron distribution in the fly body and to protect flies against some infections. The goal of this study was to better understand the physiological functions of Tsf1 in D. melanogaster by 1) investigating Tsf1 null phenotypes, 2) determining tissue-specific localization of Tsf1, 3) measuring the concentration of Tsf1 in hemolymph, 4) testing Tsf1 for bacteriostatic activity, and 5) evaluating the effect of metal and paraquat treatments on Tsf1 abundance. Flies lacking Tsf1 had more iron than wild-type flies in specialized midgut cells that take up iron from the diet; however, the absence of Tsf1 had no effect on the iron content of whole midguts, fat body, hemolymph, or heads. Thus, as previous studies have suggested, Tsf1 appears to have a minor role in iron transport. Tsf1 was abundant in hemolymph from larvae (0.4 μM), pupae (1.4 μM), adult females (4.4 μM) and adult males (22 μM). Apo-Tsf1 at 1 μM had bacteriostatic activity whereas holo-Tsf1 did not, suggesting that Tsf1 can inhibit microbial growth by sequestering iron in hemolymph and other extracellular environments. This hypothesis was supported by detection of secreted Tsf1 in tracheae, testes and seminal vesicles. Colocalization of Tsf1 with an endosome marker in oocytes suggested that Tsf1 may provide iron to developing eggs; however, eggs from mothers lacking Tsf1 had the same amount of iron as control eggs, and they hatched at a wild-type rate. Thus, the primary function of Tsf1 uptake by oocytes may be to defend against infection rather than to provide eggs with iron. In beetles, Tsf1 plays a role in protection against oxidative stress. In contrast, we found that flies lacking Tsf1 had a typical life span and greater resistance to paraquat-induced oxidative stress. In addition, Tsf1 abundance remained unchanged in response to ingestion of iron, cadmium or paraquat or to injection of iron. These results suggest that Tsf1 has a limited role in protection against oxidative stress in D. melanogaster.

Mitoquinone mitigates paraquat-induced A549 lung epithelial cell injury by promoting MFN1/MFN2-mediated mitochondrial fusion.

Paraquat (PQ) poisoning often leads to severe lung injuries, in which the mitochondria damage plays a critical role. Mitoquinone (MitoQ), a newly designed mitochondria-targeted antioxidant, has been proved for its benefit in mitochondria protection. However, the role of MitoQ in PQ-induced lung injury remains unclear. Thus, this study was performed to investigate the effect of MitoQ on PQ-induced lung injury and its underlying mechanisms. Our work showed that PQ caused the inhibition of A549 lung epithelial cell viability in a dose-dependent manner, while MitoQ remarkably mitigated the PQ-induced cell viability suppression. Besides this, PQ-mediated apoptosis of A549 cells was significantly attenuated by MitoQ, as indicated by the TUNEL assay and mitochondria membrane potential assay. Moreover, the intracellular reactive oxygen species (ROS) production was also dramatically suppressed when cotreated MitoQ with PQ. This could be ascribed to enhanced mitochondrial fusion mediated by Mitofusin 1 (MFN1)/Mitofusin 2 (MFN2), because MitoQ preserved mitochondrial network integrity, as reflected by MitoTracker staining, and MitoQ also increased the expression of MFN1/MFN2 in A549 cells after PQ treatment. Our data suggested MitoQ mitigated PQ-induced lung epithelial cell injury by promoting MFN1/MFN2-mediated mitochondrial fusion, and MitoQ might be a potential candidate drug for the treatment of PQ-induced lung injury.

Cannabinoid Analogue WIN 55212-2 Protects Paraquat-Induced Lung Injury and Enhances Macrophage M2 Polarization.

WIN 55212–2 is an endocannabinoids analogue that has been reported to have anti-inflammatory and anti-fibrosis effects on different models. In this study, we investigated the protective effects of WIN 55212–2 on paraquat (PQ)-induced poison on mice especially on lung injury. Mice were administrated with different dose of PQ and thereafter treated with 0.2 mg/kg or 1 mg/kg WIN 55212–2. The survival of mice was recorded during 4 weeks of observation. Twenty-eight days after PQ treatment, the cell population and inflammatory factors IL-6, IL-10, and TNF-α were measured in bronchoalveolar lavage fluid (BALF). Pulmonary fibrosis was evaluated by Masson staining. Our results showed that WIN 55212–2 treatment reduced PQ-induced mortality of mice in a dose dependent manner. It decreased the number of inflammation-associated cells, as well as the level of pro-inflammatory factors in BALF (P < 0.05). WIN 55212–2 increased M2 cells in BALF (P < 0.05), improved the lung histology, reduced fibrosis formation, and decreased TGF-β, α-SMA and PDGFRa expression. The protective effects of WIN 55212–2 on PQ-induced lung injury and fibrosis were associated with an increase inM2 cells and increased expressions of IL-10, CD163, and CD206, suggesting that polarization of M2 macrophages may be involved in WIN 55212–2 protective effects on PQ-induced lung injury.

Effects of Vitamin E on Chronic Haematoxicity of Paraquat Exposed Male Albino Rats (Rattus norvegicus)

Paraquat is an environmental pollutant that is associated with some disorders including alteration of some harmatological indices and is a concern to public health. Vitamin E has antioxidant property and other characteristic roles that ameliorate toxic effect. 200 male albino rats weighing 0.2±0.02kg on the average were divided into four main groups (A, B, C, and D) with 50 rats in one group. The “A” group was not served paraquat solution and was used as the control group. Group “B”, “C”, “D” being the treatment group were given dose rates of paraquat of 0.02g, 0.04g, and 0.06g, of paraquat per kg rat respectively every two weeks for three months. The main groups further had subgroups. “A”, “A0” and “AVE”; “B”, “B0” and “BVE”; “C” had “C0” and “CVE”; and “D”, “D0” and “DVE” subgroups. Vitamin E was not given to subgroups “A0”, “B0”, “C0” and “D0” subgroups while “AVE”, “BVE”, “CVE” and “DVE” were fed orally with 500mg of vitamin E therapy every week. Treatment with vitamin E began three months after paraquat treatment. At the end of the weekly treatment with vitamin E for a month, the rats were sacrificed and their blood samples were obtained and analyzed for PCV, Hb, WBC, neutrophil and lymphocyte. A0, B0, C0 and D0 intergroup comparison was statistically significant, p-value&lt;0.05 in PCV and Hb levels while their WBC, neutrophil and lymphocyte had no statistical significance. Ave, Be, Cve and Dve intergroup comparison was statistically significant, p-value&lt;0.05 in PCV and Hb levels while WBC, lymphocyte and neutrophils had no statistical significance among the groups. Intra group comparison showed that only PCV and Hb were significant between groups, p-value&lt;0.05. This study confirms that vitamin E is potent in treating paraquat toxicity in male albino rats on one month of weekly treatment.

Application of trinity emergency nursing pathway in comprehensive treatment of acute paraquat poisoning.

Application of trinity emergency nursing pathway in comprehensive treatment of acute paraquat poisoning.