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Journal of Water and Health Jun 2024This study evaluated pesticide exposure practices, and the potential health risks of drinking water and consuming fish from the cultivated wetlands of Ndop, Cameroon....
This study evaluated pesticide exposure practices, and the potential health risks of drinking water and consuming fish from the cultivated wetlands of Ndop, Cameroon. Six hundred and twenty-six questionnaires were conveniently administered to farmers (≥ 26 years old) in a cross-sectional study to assess exposure practices and dietary risks. The Chi-square and Pearson correlation coefficients were used to establish relationships between variables. The PRIMET model was used to predict a worst-case dietary risk. The pesticide handling practices of 90% of farmers were inadequate. Chlorpyriphos, lambda-cyhalothrin, fipronil, and paraquat dichloride posed a possible dietary risk at recommended and applied doses, with chlorpyrifos having the highest exposure toxicity ratio (ETR = 36.72). Paraquat dichloride, fipronil, and lambda-cyhalothrin posed a possible dietary risk at 26.3%, 58.3%, and 62.2% of their recommended concentrations, respectively. Remarkably, the dietary risk for cypermethrin was acceptable at 5.8 times its recommended dose (ETR = 0.29). The significant positive correlation (p = 0.000) between PEC and ETR, suggests a possible health risk of consuming fish and drinking water harvested from the wetlands, thus the need for replacing pesticides posing possible risks at lower or recommended concentrations with less toxic alternatives and to train farmers on pesticide application practices.
Topics: Drinking Water; Animals; Fishes; Risk Assessment; Humans; Water Pollutants, Chemical; Wetlands; Pesticides; Cameroon; Cross-Sectional Studies; Food Contamination; Diet; Dietary Exposure; Adult; Agriculture; Surveys and Questionnaires
PubMed: 38935458
DOI: 10.2166/wh.2024.057 -
Antioxidants (Basel, Switzerland) Jun 2024Oxidative stress is a key factor causing mitochondrial dysfunction and retinal ganglion cell (RGC) death in glaucomatous neurodegeneration. The cyclic adenosine...
Oxidative stress is a key factor causing mitochondrial dysfunction and retinal ganglion cell (RGC) death in glaucomatous neurodegeneration. The cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway is involved in mitochondrial protection, promoting RGC survival. Soluble adenylyl cyclase (sAC) is a key regulator of the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway, which is known to protect mitochondria and promote RGC survival. However, the precise molecular mechanisms connecting the sAC-mediated signaling pathway with mitochondrial protection in RGCs against oxidative stress are not well characterized. Here, we demonstrate that sAC plays a critical role in protecting RGC mitochondria from oxidative stress. Using mouse models of oxidative stress induced by ischemic injury and paraquat administration, we found that administration of bicarbonate, as an activator of sAC, protected RGCs, blocked AMP-activated protein kinase activation, inhibited glial activation, and improved visual function. Moreover, we found that this is the result of preserving mitochondrial dynamics (fusion and fission), promoting mitochondrial bioenergetics and biogenesis, and preventing metabolic stress and apoptotic cell death. Notably, the administration of bicarbonate ameliorated mitochondrial dysfunction in RGCs by enhancing mitochondrial biogenesis, preserving mitochondrial structure, and increasing ATP production in oxidatively stressed RGCs. These findings suggest that activating sAC enhances the mitochondrial structure and function in RGCs to counter oxidative stress, consequently promoting RGC protection. We propose that modulation of the sAC-mediated signaling pathway has therapeutic potential acting on RGC mitochondria for treating glaucoma and other retinal diseases.
PubMed: 38929182
DOI: 10.3390/antiox13060743 -
BioRxiv : the Preprint Server For... Jun 2024Flavin-containing monooxygenases (FMOs) are a conserved family of xenobiotic enzymes upregulated in multiple longevity interventions, including nematode and mouse...
Flavin-containing monooxygenases (FMOs) are a conserved family of xenobiotic enzymes upregulated in multiple longevity interventions, including nematode and mouse models. Previous work supports that promotes longevity, stress resistance, and healthspan by rewiring endogenous metabolism. However, there are five FMOs and five mammalian FMOs, and it is not known whether promoting longevity and health benefits is a conserved role of this gene family. Here, we report that expression of promotes lifespan extension and paraquat stress resistance downstream of both dietary restriction and inhibition of mTOR. We find that overexpression of in just the hypodermis is sufficient for these benefits, and that this expression significantly modifies the transcriptome. By analyzing changes in gene expression, we find that genes related to calcium signaling are significantly altered downstream of expression. Highlighting the importance of calcium homeostasis in this pathway, overexpressing animals are sensitive to thapsigargin, an ER stressor that inhibits calcium flux from the cytosol to the ER lumen. This calcium/ interaction is solidified by data showing that modulating intracellular calcium with either small molecules or genetics can change expression of and/or interact with to affect lifespan and stress resistance. Further analysis supports a pathway where modulates calcium homeostasis downstream of activating transcription factor-6 ( ), whose knockdown induces and requires expression. Together, our data identify as a longevity- promoting gene whose actions interact with known longevity pathways and calcium homeostasis.
PubMed: 38915593
DOI: 10.1101/2024.05.17.594584 -
Ecotoxicology and Environmental Safety Jun 2024Paraquat (PQ) is a widely used herbicide that poisons human by accident or intentional ingestion. PQ poisoning causes systemic inflammatory response syndrome (SIRS)...
BACKGROUND
Paraquat (PQ) is a widely used herbicide that poisons human by accident or intentional ingestion. PQ poisoning causes systemic inflammatory response syndrome (SIRS) resulting in acute lung injury (ALI) with an extremely high mortality rate. Blood trematode Schistosoma japonicum-produced cystatin (Sj-Cys) is a strong immunomodulatory protein that has been experimentally used to treat inflammation related diseases. In this study, Sj-Cys recombinant protein (rSj-Cys) was used to treat PQ-induced lung injury and the immunological mechanism underlying the therapeutic effect was investigated.
METHODS
PQ-induced acute lung injury mouse model was established by intraperitoneally injection of 20 mg/kg of paraquat. The poisoned mice were treated with rSj-Cys and the survival rate was observed up to 7 days compared with the group without treatment. The pathological changes of PQ-induced lung injury were observed by examining the histochemical sections of affected lung tissue and the wet to dry ratio of lung as a parameter for inflammation and edema. The levels of the inflammation related cytokines IL-6 and TNF-α and regulatory cytokines IL-10 and TGF-β were measured in sera and in affected lung tissue using ELISA and their mRNA levels in lung tissue using RT-PCR. The macrophages expressing iNOS were determined as M1 and those expressing Arg-1 as M2 macrophages. The effect of rSj-Cys on the transformation of inflammatory M1 to regulatory M2 macrophages was measured in affected lung tissue in vivo (EKISA and RT-PCR) and in MH-S cell line in vitro (flow cytometry). The expression levels of TLR2 and MyD88 in affected lung tissue were also measured to determine their role in the therapy of rSj-Cys on PQ-induced lung injury.
RESULT
We identified that treatment with rSj-Cys significantly improved the survival rate of mice with PQ-induced lung injury from 30 % (untreated) to 80 %, reduced the pathological damage of poisoning lung tissue, associated with significantly reduced levels of proinflammatory cytokines (IL-6 from 1490 to 590 pg/ml, TNF-α from 260 to 150 pg/ml) and increased regulatory cytokines (IL-10 from360 to 550 pg/ml, and TGF-β from 220 to 410 pg/ml) in both sera (proteins) and affected lung tissue (proteins and mRNAs). The polarization of macrophages from M1to M2 type was found to be involved in the therapeutic effect of rSj-Cys on the PQ-induced acute lung injury, possibly through inhibiting TLR2/MyD88 signaling pathway.
CONCLUSIONS
Our study demonstrated the therapeutic effect of rSj-Cys on PQ poisoning caused acute lung injury by inducing M2 macrophage polarization through inhibiting TLR2/MyD88 signaling pathway. The finding in this study provides an alternative approach for the treatment of PQ poisoning and other inflammatory diseases.
PubMed: 38905933
DOI: 10.1016/j.ecoenv.2024.116615 -
Tissue & Cell Jun 2024Paraquat (PQ), is an extensively used herbicide and is a well-established powerful neurotoxin. However, the mechanism underlying its neurotoxicity still needs further...
Effect of Selenium nanoparticles on Paraquat-induced-neuroinflammation and oligodendocyte modulation: Implication of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway.
BACKGROUND
Paraquat (PQ), is an extensively used herbicide and is a well-established powerful neurotoxin. However, the mechanism underlying its neurotoxicity still needs further investigation.
AIM OF WORK
The study investigated the pathogenesis of PQ-induced neuroinflammation of the substantia nigra pars compacta (SNPC) and cerebellum and evaluated the potential effect of selenium nanoparticles (SeN) against such neurotoxicity.
METHODS
Thirty-six mice were randomly divided into three groups; Control group, PQ group: mice received PQ 10 mg/kg (i.p), and PQ + SeN group; mice received PQ in addition to oral SeN 0.1 mg/kg. All regimens were administered for 14 days. The mice's brains were processed for biochemical, molecular, histological, and immune-histochemical assessment.
RESULTS
SeN increased the SNPC and cerebellum antioxidants (reduced glutathione, glutathione peroxidase, and superoxide dismutase 1) while decreasing malondialdehyde concentration. Also, SeN increased the anti-inflammatory interleukin (IL)-10 and decreased the pro-inflammatory IL-1β and -6 along with improving the angiogenic nitric oxide and reducing caspase-1. Further, western blots of phosphorylated Janus kinase (JAK2)/signal transducer and activator of transcription3 (STAT3) proteins showed a significant decline. Those improving effects of SeN on SNPC, and cerebellum were supported by the significantly preserved dopaminergic and Purkinje neurons, the enhanced myelin fibers on Luxol fast blue staining, and the marked increase in Olig-2, Platelet-derived growth factor-alpha, and tyrosine hydroxylase immunoreactivity.
CONCLUSION
SeN could mitigate PQ-induced neurotoxicity via its antioxidant, anti-inflammatory, and antiapoptotic properties.
PubMed: 38905876
DOI: 10.1016/j.tice.2024.102454 -
World Journal of Clinical Cases Jun 2024Following the withdrawal of paraquat, diquat (DQ) has emerged as the predominant herbicide. When people come into contact with or ingest DQ, may lead to poisoning and...
Following the withdrawal of paraquat, diquat (DQ) has emerged as the predominant herbicide. When people come into contact with or ingest DQ, may lead to poisoning and potentially fatal outcomes. Reports suggest that the mortality of DQ poisoning can be as high as 50%. DQ poisoning can be categorized as mild, moderate to severe or fulminant. In cases of fulminant poisoning, victims often succumb to multiple organ failure within 48 h. This presents a significant challenge in the clinical management. Scholars have discovered that oxidative stress, inflammatory injury, and cell apoptosis play crucial roles in the DQ poisoning. However, the underlying connection of the extensive organ damage remains unknown. The abnormal function and activity of endothelial cells (EC) should play a crucial role in tissue damage caused by DQ due to rich microcirculation and high sensitivity to perfusion in the vulnerable organs. However, reports on DQ-induced EC injury is rare. We made a preliminary discovery-the presence of severe vascular endothelial damage in the kidneys and lungs affected by DQ. Therefore, we hypothesize that DQ poisoning may be attributed to EC damage, ultimately resulting in multiple organ failure.
PubMed: 38898842
DOI: 10.12998/wjcc.v12.i17.2917 -
Chemosphere Jun 2024In recent years, the surge in plastic production has led to pervasive pollution across all environments, earning us the title of inhabiting a "plastic world."...
In recent years, the surge in plastic production has led to pervasive pollution across all environments, earning us the title of inhabiting a "plastic world." Consequently, this research endeavors to explore alterations in biochemical parameters, liver enzymes, and tissue integrity within the gills, intestines, and liver of black fish subjected to polyvinyl chloride (PVC) microplastics and paraquat herbicide, both individually and in combination. For this purpose, we allocated 90 blackfish specimens into 9 groups consisting of 10 individuals each through random selection. Following a period of 28 days, we carried out an assessment to investigate the toxic effects of PVC and paraquat, both separately and in combination. Subsequently, The results indicate that the number of red blood cells (RBCs, millions/mm) in all studied groups (Group G: 3.6 ± 0.18; Group H: 3.5 ± 0.17; and Group I: 3.2 ± 0.16) is significanly lower than the control group (Pvalue<0.05). The glucose levels in all studied groups (Group B: 47 ± 5.12; Group C: 48 ± 3.79; Group D: 51 ± 4.14; Group E: 48 ± 5.37; Group F: 53 ± 7.48; Group G: 53 ± 9.24; Group H: 58 ± 10.43; and Group I: 61 ± 8.71) are higher than the control group (46 ± 3.71). The results indicate that the levels of AST enzyme in all studied groups (group B: 30 ± 0.17; group C: 32 ± 1.61; group D: 34 ± 1.92; group E: 33 ± 1.17; group F: 38 ± 2.27; group G: 38 ± 1.71; group H: 43 ± 2.15; and group I: 46 ± 2.33). Groups F, G, H, and I exhibit significantly higher levels of AST enzyme compared to the control group, with a p-value<0.05. Morphological changes observed in erythrocytes include deformation and cell vacuolation. The maximum amount of changes in the morphology of erythrocytes occurs when black fish is exposed to 2 mg/L of PVC and 0.4 mg/L of paraquat (group I). The histological harm caused by the combination of PVC and paraquat is significant. Findings indicate that increasing the concentration of both microplastics and paraquat enhances their toxicity when combined. Consequently, it's imperative to assess the toxic impact of microplastics (MPs) and paraquat individually, as well as in combination, on aquatic organisms to safeguard them from the detrimental effects of these substances.
PubMed: 38897326
DOI: 10.1016/j.chemosphere.2024.142643 -
EJNMMI Research Jun 2024Paraquat (PQ) -induced pulmonary fibrosis poses a significant medical challenge due to limited treatment options and high mortality rates. Consequently, there is an...
BACKGROUND
Paraquat (PQ) -induced pulmonary fibrosis poses a significant medical challenge due to limited treatment options and high mortality rates. Consequently, there is an urgent need for early diagnosis and accurate staging to facilitate appropriate treatment strategies. In this study, we assessed the diagnostic potential of [F]F-FAPI-42 PET/CT imaging for early detection and disease staging in a rat model of PQ-induced lung fibrosis.
METHODS
After administering 80 mg/kg of PQ orally to Sprague-Dawley rats, we intravenously injected 3-3.5 MBq of [F]F-FAPI-42 on day 7, 14, and 21 post-dosing. Dynamic PET/CT imaging was carried out for one hour immediately after the administration of [F]F-FAPI-42. Subsequently, the lung tissues were collected for Hematoxylin and Eosin (HE) staining, Masson's trichrome staining, and NOTA-FAPI-04-MB fluorescent probe staining. Data analysis was performed using the Imalytics preclinical software, and the mean standardized uptake value (SUV) was calculated.
RESULTS
PET signals revealed that in areas with evident lesions on CT, the SUV on day 14 was significantly higher than on day 7 and 21, indicating that changes in fibrosis activity levels contribute to the staging of pulmonary fibrosis. Additionally, the NOTA-FAPI-04-MB fluorescent probe staining also demonstrated the most pronounced probe uptake on day 14. In regions without apparent lesions on CT, the SUV gradually increased from day 7 to day 21, reflecting ongoing fibrotic activity. Moreover, HE staining and Masson's trichrome staining did not reveal pulmonary fibrosis, while PET imaging was able to detect it, serving the purpose of early diagnosis. At 30 min and 60 min, the target-to-background ratio (TBR) of the PQ groups on day 7, 14, and 21 was significantly higher than the control group, suggesting a high specificity of [F]F-FAPI-42 binding to activated fibroblasts.
CONCLUSION
[F]F-FAPI-42 PET/CT imaging enables early diagnosis and staging of PQ-induced pulmonary fibrosis, demonstrating its feasibility and potential for characterizing early disease stages.
PubMed: 38888802
DOI: 10.1186/s13550-024-01118-1 -
Research Square Jun 2024Genetic mitochondrial diseases are a major challenge in modern medicine, impacting around 1:4,000 individuals. Leigh syndrome is the most common pediatric presentation...
BACKGROUND
Genetic mitochondrial diseases are a major challenge in modern medicine, impacting around 1:4,000 individuals. Leigh syndrome is the most common pediatric presentation of mitochondrial disease. There are currently no effective clinical treatments for mitochondrial disease. In humans, patients are often treated with antioxidants, vitamins, and strategies targeting energetics. The vitamin-E related compound vatiquinone (EPI-743, α-tocotrienol quinone) has been the subject of at least 19 clinical trials in the US since 2012, but the effects of vatiquinone on an animal model of mitochondrial disease have not yet been reported. Here, assessed the impact of vatiquinone on disease progression and in two animal models of mitochondrial disease.
METHODS
The efficacy of vatiquinone was assessed using human fibroblasts treated with the general mitochondrial oxidative stress inducer paraquat, the GPX4 inhibitor RSL3, or the glutathione synthase inhibitor BSO in combination with excess iron. The therapeutic potential of vatiquinone was assessed using tamoxifen-induced mouse model for GPX4 deficiency and the knockout mouse model of Leigh syndrome. In both models, animals were treated daily with vatiquinone or vehicle and relevant disease endpoints were assessed.
RESULTS
Vatiquinone robustly prevented death in cultured cells induced by RSL3 or BSO/iron, but had no effect on paraquat induced cell death. Vatiquinone had no impact on disease onset, progression, or survival in either the tamoxifen-inducible GPX4 deficient model or the (-/-) mouse model, though the drug may have reduced seizure risk.
CONCLUSIONS
Vatiquinone provided no benefit to survival in two mouse models of disease, but may prevent seizures in the (-/-) model. Our findings are consistent with recent press statements regarding clinical trial results and have implications for drug trial design and reporting in patients with rare diseases.
PubMed: 38883711
DOI: 10.21203/rs.3.rs-4202689/v1 -
MethodsX Jun 2024This paper provides a complete protocol for studying the effects of inhaled paraquat (PQ), a toxic herbicide that has negative effects systemically and on the lungs. The...
This paper provides a complete protocol for studying the effects of inhaled paraquat (PQ), a toxic herbicide that has negative effects systemically and on the lungs. The protocol aims to evaluate the effects of aerosolized PQ exposure on lung and systemic injury in an animal model, which will provide significant information for therapeutic interventions for PQ-induced pulmonary and systemic damage. The protocol involves the following key components: 1. Study groups: By including control, non-treated aerosolized PQ-exposed, and treated PQ-exposed animals with various agent groups in the experiment, lung and systemic injury in each group could be evaluated, and different measured parameters could be compared among groups. 2. PQ exposure: Animals in the PQ-exposed groups are subjected to PQ aerosol inhalation, simulating occupational or accidental exposure in farmers working with this herbicide. 3. Assessment measures: To determine the degree of lung and systemic injury and its physiological effects, several assessments, such as biochemical markers, histopathological analysis, and functional tests, are used. The protocol offers reliable and accurate results by using standardized methods and data collection. The effect of PQ exposure on lung and systemic injury could be evaluated by statistical analysis of the collected data, which also makes it easier to identify possible protective agents or interventions. This comprehensive evaluation protocol provides an essential basis for studying the mechanisms behind PQ-induced lung and systemic injury and assessing the effectiveness of preventative or therapeutic strategies in minimizing its adverse effects.
PubMed: 38883591
DOI: 10.1016/j.mex.2024.102782