Paraquat Toxicity Research Articles

Histological and Biochemical Effects of Lutein on Paraquat-induced Renal Toxicity in Wistar Rats

Introduction: Paraquat (PQ) poisoning in humans predominantly results from the generation of reactive oxygen species (ROS). To date, no proven antidote exists for PQ poisoning, which is characterized by severe kidney injury and high mortality rates globally. However, free radical scavengers and antioxidant agents have shown potentials to mitigate PQ toxicity. Aim: The study is aimed at investigating lutein, an antioxidant, for possible mitigation of paraquat-induced renal toxicity. Study Design: Preclinical experimental study. Place and Duration of Study: Department of Anatomy, Obafemi Awolowo University (OAU), Nigeria, between 2022 and 2023. Methods: Forty wistar rats weighing 150-180 grammes were randomly grouped (A to E) for this study. Paraquat (PQ) toxicity was induced in groups B to E. Lutein was administered at graded doses of 50 mg/kg, 100 mg/kg and 150 mg/kg to groups C to E for twenty-one days respectively. Group A (positive control) was given only normal saline, while group B had paraquat only. Twenty-four hours after the last administration, urine and blood samples were collected and the animals were sacrificed before the excision of the kidneys. Results: A marked histological distortion, which was characterized by compromised Bowman's space and renal tubule dimensions, was observed in Group B. In contrast, the lutein-treated groups exhibited dose-dependent improvements, with outcomes comparable to the control group. Notably, Group B showed significant elevations in plasma creatinine (P = 0.003) and urine protein (P = 0.001), accompanied by reduced plasma protein (P = 0.004), relative to the treated groups. However, Group E, which received the highest lutein dose, demonstrated substantial improvement in histoarchitectural and biochemical findings similar to the control group." Conclusion: This study demonstrated significant alterations in the histoarchitecture and biochemical profiles of renal tissue following paraquat exposure. Notably, the lutein-treated groups exhibited substantial improvement, with results comparable to the control group. These findings suggest that lutein may possess potential therapeutic properties to mitigate paraquat-induced renal toxicity.

Effects of Lutein on the Body Weights, Hepato-renal DNA and Antioxidant Capacity Following Paraquat-induced Toxicity in Wistar Rats

Introduction: Paraquat is a leading cause of herbicide-related fatalities worldwide. Its high mortality rate is attributed to its inherent generation of ROS-mediated toxicity, and lack of effective treatment till date. Lutein is an antioxidant with free radical scavenging ability, which may contribute to its protective effects and possible DNA preservation. Objective: The study is evaluating the effects of lutein on body weights and hepato-renal antioxidant capacity with DNA quantification following paraquat toxicity in wistar rats. Methods: Thirty-five male Wistar rats (150-180g) rats were randomly divided into five equal groups (A-E). Paraquat toxicity was induced in Groups B-E with 5mg/kg for three days. Group A received normal saline only, while Group B was given paraquat only. Thereafter, Groups C-E received varying doses of lutein (50, 100, 150mg/kg) for 21 days. Their body weights were recorded twice weekly using a digital balance. The animals were sacrificed and their liver with kidneys were excised and processed. The photomicrographs were taken at various magnifications while Image J software was employed for DNA densities. The total antioxidant capacity (TAC) was assessed by Prieto method. Results: There was significant reductions in the body weights, (p=0.00) hepato-renal DNA densities (p=0.00, p=0.01) and antioxidant capacities of the PQ-only group relative to the positive control A in both liver and kidneys (p-0.01, p=0.02). However, the lutein-treated groups had dose-dependent similar features with the control, which had normal histo-morphological feature. The highest dose of lutein showed the best correlation with the control. Conclusion: This study showed significant alterations in body weights, hepato-renal DNA densities and antioxidant capacities especially in the PQ-only group. Meanwhile, the lutein-treated groups, especially at high dosages, showed significant improvements in the indices similar to the control. Hence, lutein may be a useful agent for attenuating paraquat toxicity.

Novel Indirect Antioxidant Activity Independent of Nrf2 Exerted by Lactic Acid Bacteria.

In recent years, the health benefits of lactic acid bacteria have garnered attention, but their antioxidant activity remains relatively underexplored. We have been analyzing the antioxidant activities of various dietary phytochemicals by assessing their ability to mitigate oxidative stressor-induced toxicity in zebrafish larvae through pretreatment. In this study, the antioxidant activities of 24 strains of heat-killed lactic acid bacteria from various origins were examined using this zebrafish assay system. The results revealed that all 24 strains possessed antioxidant activity that reduces hydrogen peroxide toxicity. Further detailed analysis using the H61 strain, which exhibited the strongest activity, showed that no direct antioxidant activity was observed in the assay system, suggesting that the detected antioxidant activity was entirely indirect. Moreover, it was found that pretreatment of zebrafish larvae with the H61 strain for more than 6 h was required to exert its antioxidant activity. This duration was similar to that required by dietary antioxidants that activate the Keap1-Nrf2 pathway, suggesting potential involvement of this pathway. However, analysis using Nrf2-knockout zebrafish revealed that the antioxidant activity of strain H61 is independent of Nrf2, indicating that it represents a novel indirect antioxidant activity that does not involve the Keap1-Nrf2 pathway. To further characterize this activity, the ability to mitigate the toxicity of oxidative stressors other than hydrogen peroxide was examined. The results indicated that while the toxicity of tert-butyl hydroperoxide was reduced, unlike with the Keap1-Nrf2 pathway, it was not effective in counteracting the toxicity of paraquat or arsenite, which generate superoxide radicals. In conclusion, we have identified a novel indirect antioxidant activity in lactic acid bacteria.

Protective Effects of Hydroalcoholic Leaf Extract of Origanum Vulgare against Paraquat-induced Lung Toxicity in Rats: The Role of the Inflammation-related Markers and Oxidative Stress

Background:: The pesticide paraquat is hazardous to both humans and animals. Lung damage is a common complication of paraquat poisoning. Objective:: This research analyzes the preventive properties of Origanum vulgare leaf extract against paraquat-induced acute pulmonary toxicity and oxidative stress. Methods:: In this experiment, the rats were assigned to five distinct groups. Group 1 served as the control, group 2 got only 25 mg/kg bw paraquat, and groups 3, 4, and 5 received paraquat and Origanum vulgare leaf extract at dosages of 200, 400, and 800 mg/kg bw, respectively. In rats, inflammation- related indicators and oxidative stress were analyzed after therapy. Results:: Compared with the control group, the levels of the serum PC, MDA, and inflammatory markers such as TNF-α, IL-6, and IL-1β remarkably rose (p < 0.05) and the pulmonary contents of the SOD, CAT, and vitamin C greatly decreased (p < 0.05) in the paraquat-only group. Origanum vulgare leaf extract administration after paraquat exposure resulted in a substantial increase in lung SOD, CAT, and vitamin C levels as well as a significant reduction in MDA, PC, and lung inflammatory markers (TNF-α, IL-6, and IL-1β) gene expression relative to the paraquat-only group. Conclusion:: Origanum vulgare leaf extract might be supplied to lessen the toxicity of paraquat, based on the findings of this research, which indicated that Origanum vulgare leaf extract has antioxidant- enhancing properties and can improve the antioxidant defense system. other: Ethic number: IR. SKUMS. REC. 1395. 151.

Biotoxicity of paraquat to lung cells mediated by endoplasmic reticulum-mitochondria interaction.

The high lethality caused by paraquat (PQ) poisoning has attracted much attention in public and human health due to its high toxicity and lethality. However, the understanding of the mechanism of PQ-induced apoptosis from the perspective of organelles, especially inter-organelle interactions, is still scarce. Exploring the linkage of multiple organelles during PQ poisoning and the molecular mechanisms of PQ poisoning under its mediation will help to gain insight into the mode of PQ poisoning at the organelle level. In this study, we observed that a certain dose of PQ gavage induced oxidative stress, mitochondrial dysfunction and endoplasmic reticulum stress in rat lung tissue cells. PQ toxicity led to the occurrence of Ca2+ overload in the endoplasmic reticulum, and the activated BIP and CHOP pathways directly/indirectly led to the expression of apoptogenic factors Caspase family factors. In addition, PQ promoted Ca2+ release from the endoplasmic reticulum and Ca2+ uptake by mitochondria, which induced the disruption of Bax/Bcl-2 channel proteins in response to the IP3R/RyR/VDAC1&2/MCU Ca2+ axis thereby leading to the release of CytoC, which ultimately induced endoplasmic reticulum stress and apoptotic cell death. In addition, 10 differential proteins were screened and validated by proteomics that may act as upstream and downstream active factors of mitochondria-endoplasmic reticulum interaction-mediated biotoxicity. Our findings provide new perspectives for researchers to explore the toxicity mechanisms of PQ to reduce their adverse effects.

Mechanisms Mediating the Combined Toxicity of Paraquat and Maneb in SH-SY5Y Neuroblastoma Cells.

Epidemiological and experimental studies have demonstrated that combined exposure to the pesticides paraquat (PQ) and maneb (MB) increases the risk of developing Parkinson's disease. However, the mechanisms mediating the toxicity induced by combined exposure to these pesticides are not well understood. The aim of this study was to investigate the mechanism(s) of neurotoxicity induced by exposure to the pesticides PQ and MB isolated or in association (PQ + MB) in SH-SY5Y neuroblastoma cells. PQ + MB exposure for 24 and 48 h decreased cell viability and disrupted cell membrane integrity. In addition, PQ + MB exposure for 12 h decreased the mitochondrial membrane potential. PQ alone increased reactive oxygen species (ROS) and superoxide anion generation and decreased the activity of mitochondrial complexes I and II at 12 h of exposure. MB alone increased ROS generation and depleted intracellular glutathione (GSH) within 6 h of exposure. In contrast, MB exposure for 12 h increased the GSH levels, the glutamate cysteine ligase (GCL, the rate-limiting enzyme in the GSH synthesis pathway) activity, and increased nuclear Nrf2 staining. Pretreatment with buthionine sulfoximine (BSO, a GCL inhibitor) abolished the MB-mediated GSH increase, indicating that MB increases GSH synthesis by upregulating GCL, probably by the activation of the Nrf2/ARE pathway. BSO pretreatment, which did not modify cell viability per se, rendered cells more sensitive to MB-induced toxicity. In contrast, treatment with the antioxidant N-acetylcysteine protected cells from MB-induced toxicity. These findings show that the combined exposure of SH-SY5Y cells to PQ and MB induced a cytotoxic effect higher than that observed when cells were subjected to individual exposures. Such a higher effect seems to be related to additive toxic events resulting from PQ and MB exposures. Thus, our study contributes to a better understanding of the toxicity of PQ and MB in combined exposures.

Study on Clinical Profile and Treatment Outcome of Acute Paraquat Poisoning in an Intensive Care Unit in Bangladesh

Background: Paraquat, one of the most widely used herbicides, is a major cause of self-harm related death in Bangladesh resulting from multiple organ failure. The primary objective aimed to identify the demographic & clinical characteristics of paraquat poisoning and the outcome of different treatment modalities. Materials and Methods: A prospective observational study was conducted over twenty-four months at the Intensive Care Unit of Dhaka Medical College Hospital, a tertiary care referral hospital.Between March 2022 and March 2024, patients presenting with acute paraquat toxicity who fulfilled inclusion and exclusion criteriawere selected by purposive sampling. A total of 42 patients were enrolled in the study.Demographic, clinical, and treatment particulars were collected. The study evaluated the outcomes, including length of stay in the intensive care unit (ICU), the need for mechanical ventilation&hemodialysisandin-hospital mortality. SPSS version 25.0 was used for statistical analysis and reporting. Results: Among the patients, 54.8% were men with a median age of 23.31 years residing in rural areas (85.7%). All cases were suicidal, primarily due to family disputes (40.5%) and personal relationship issues (21.4%). Symptoms included shortness of breath (40.5%), disorientation (28.6%), difficulty in swallowing (14.3%), vomiting (9.5%), and low urine output (7.1%). Most ICU admissions occurred after 24 hours postingestion (59.5%). Organ involvement included acute kidney injury (57.14%), acute respiratory distress syndrome (50%), hepatic impairment (14.3%), pulmonary fibrosis (14.3%), and septic shock (2.4%). Methylprednisolone was administered to 21 patients (50%), with an equal number also receiving methylprednisolone plus cyclophosphamide (50%). Only 10 (23.80%) patients received gastric lavage.The median ICU stay was 6 days (IQR 4-9), while the Median hospital stay was 8 days (IQR 1-12). In-hospital mortality was high, and 41 out of 42 patients (97.8%) died. Conclusion: The rural population is mostly affected by paraquat poisoning for its easy availability,and clinical presentations, particularly pulmonary, renal and multi-systeminvolvement, are significantly associated with high mortality with the limited role of different treatment approaches. J MEDICINE 2024; 25: 129-135

Molecular, Biochemical and Histological Assessment in Paraquat Induced Neurotoxicity: Restoring Role of Nano-curcumin in an Experimental Study

Abstract Background: Paraquat (PQ) is known to cause damage to various organs, including the brain. Although curcumin have anti-inflammatory and anti-oxidant properties, it is not yet clear how they relate to PQ-induced neurotoxicity. This study’s objective was to compare the effects of curcumin and nanocurcumin on PQ-induced neurotoxicity in male rats. Methods: 36 rats were randomly divided into 6 groups. control subjects and animals poisoned with PQ that received treatment with or without curcumin and nano-curcumin for 7 days. The brain tissues were collected at the end of this period. Total antioxidant capacity (TAC), lipid peroxidation (LPO), and total thiol groups (TTG) were assessed by using spectrophotometry. Moreover, the histopathology of brain and antioxidant gene expression were assessed by biochemical and reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Results: Curcumin and nanocurcumin therapy alleviated the PQ-triggered oxidative stress in brain tissue by raising the levels of anti-oxidant biomarkers like TAC and TTG, up-regulating the expression of Nrf2, HO-1, and NQO-1, reducing the levels of oxidative stress indices like LPO, and down- regulating the expression of Keap-1 in brain tissue. Conclusions: Treatment with curcumin and nano-curcumin improves brain function in PQ toxicity and nanocurcumin was more advantageous than ordinary curcumin.

Antioxidant Effect of Lemongrass (Cymbopogon citratus) Extract on Paraquat-Induced Oxidative Stress in Sheep Red Blood Cells Using In-vitro Phytochemical Analysis

Aims: Oxidative stress, which causes harm to cells, is a significant factor in many diseases. Red blood cells are easily damaged by free radicals. Lemongrass has powerful abilities to fight these free radicals’ because it contains a lot of phytochemicals. The study examined how effective lemongrass is in protecting red blood cells from damage caused by Paraquat. Additionally, phytochemicals present in lemongrass are also analysed. Methodology: The preparation of lemongrass leaf extract involved drying and grinding the leaves, followed by extraction with acetone using the Soxhlet method. Phytochemical analysis was done to reveal the presence of alkaloids, saponins, flavonoids, tannins, phenols, and acids. A 10% RBC suspension was prepared from sheep blood. Oxidative stress was induced in RBCs using Paraquat, Ascorbic acid, and the extract. Antioxidant analysis included protein concentration via the Lowry method, Thiobarbituric acid reactive substance (TBARS) estimation for lipid peroxidation, Glutathione (GSH) estimation, and Superoxide dismutase (SOD) activity assay. Statistical analysis was performed using GraphPad Prism, with significance set at p<0.05. Results: The phytochemical analysis revealed the presence of flavonoids, terpenoids, saponin, and tannin in lemongrass, while no acids or alkaloids were detected in the plant. In Group II exposed to Paraquat toxicity, total protein decreased significantly compared to the control group (10.24±0.53 mg/dl to 6.3±0.49 mg/dl). TBARS activity notably increased in Paraquat-treated group (629.7±2.85) compared to control (398.8±3.51), while Lemongrass and ascorbic acid treatments showed significant decreases (513.05±4.54 and 504.01±1.97, respectively). SOD and GSH levels decreased significantly in Paraquat-treated group (6.08±0.4 and 80.86±4.9 µg/mg of protein) compared to control (11.13±1.1 and 109.81±8.6, respectively), but Lemongrass treatment increased levels (14.12±2.0 and 114.8±4.5 µg GSH/mg of protein). Lemongrass demonstrated pronounced protective effects against oxidative stress, normalizing SOD levels and increasing GSH levels, comparable to ascorbic acid treatment. Conclusion: The study successfully induced oxidative stress in RBCs with Paraquat, presenting avenues for further exploration in understanding cellular responses. Additionally, the research highlights Lemongrass's significant preventive impact (100μg), possibly attributed to its bioactive phytochemicals, including flavonoids, phenols, saponins, and tannins. This underscores Lemongrass's potential in countering oxidative damage induced by Paraquat in RBCs.

Fatal Triad: Spontaneous Pneumothorax, Pneumomediastinum, and Pneumorrhachis in a Case of Paraquat Ingestion

Objective: Dependency on agriculture and the unregulated sale of paraquat makes it an easy alternative for homicidal and suicidal use in developing nations. It kills by multiorgan failure, predominantly pulmonary fibrosis, and ARDS. We report a case of alleged paraquat ingestion with spontaneous pneumothorax, spontaneous pneumomediastinum, and pneumorrhachis. Aim is to reinforce the importance of a high index of suspicion in early diagnosis when the above findings are present with ARDS in absence of trauma and a history of alleged substance ingestion. Case Presentation: A 35-year-old male presented with loose stool occasionally bloody, oral ulcers, yellow discoloration of eyes with fever, and decreased urine output for three days after consuming some substance with his seafood. On examination, he had yellow discoloration of eyes and oral mucosa along with multiple ulcers on the buccal region as well as the dorsum of the tongue and lateral margins with generalized subcutaneous emphysema. In addition, decreased air entry in the bilateral lung field and muffled heart sounds were present. He had an acute hepatorenal failure and severe metabolic acidosis with respiratory failure. Urine tested positive for myoglobin and muscle enzymes (creatinine kinase and lactate dehydrogenase (LDH)) were raised. He was intubated and shifted to the intensive care unit. Injectable N-acetyl cysteine (NAC) for acute liver failure was started with empirical antibiotics and intravenous fluids. We supplemented thiamine and vitamin K, and hemodialysis was done in view of progressive renal failure. Radiological evaluation showed spontaneous pneumothorax, pneumomediastinum, and pneumorrhachis which were managed conservatively. His respiratory parameters worsened despite maximal ventilatory support. Renal failure and metabolic acidosis worsened in spite of hemodialysis. He succumbed to his illness on day five of admission and seven days after toxin ingestion. Conclusion: We recommend that the sale of paraquat be restricted and regulated to avoid its use for suicidal and homicidal purposes. More research is required to find measures to intervene early and prevent pulmonary fibrosis. We propose that paraquat toxicity be considered early in a patient with the triad in an atraumatic setting with acute respiratory distress syndrome (ARDS).

Glycyl-l-histidyl-l-lysine prevents copper- and zinc-induced protein aggregation and central nervous system cell death in vitro.

Common features of neurodegenerative diseases are oxidative and inflammatory imbalances as well as the misfolding of proteins. An excess of free metal ions can be pathological and contribute to cell death, but only copper and zinc strongly promote protein aggregation. Herein we demonstrate that the endogenous copper-binding tripeptide glycyl-l-histidyl-l-lysine (GHK) has the ability to bind to and reduce copper redox activity and to prevent copper- and zinc-induced cell death in vitro. In addition, GHK prevents copper- and zinc-induced bovine serum albumin aggregation and reverses aggregation through resolubilizing the protein. We further demonstrate the enhanced toxicity of copper during inflammation and the ability of GHK to attenuate this toxicity. Finally, we investigated the effects of copper on enhancing paraquat toxicity and report a protective effect of GHK. We therefore conclude that GHK has potential as a cytoprotective compound with regard to copper and zinc toxicity, with positive effects on protein solubility and aggregation that warrant further investigation in the treatment of neurodegenerative diseases.

Effect of Paraquat toxicity on lung and kidney organs on histopathological image assessment

Background: Paraquat is one of the active ingredients of the gramoxone type herbicide, which has very high toxicity so that it can cause poisoning and death. Paraquat causes direct cell damage by producing free radicals, which can cause pulmonary fibrosis and kidney failure. This study aims to analyze the effects of paraquat toxicity on the lungs and kidneys on histopathological features. Methods: This research is an experimental research post-test only control group design. The research subjects used stored biological material in the form of 12 lung and kidney organ samples from white rats (Rattus norvegicus) that had been treated in previous research, which were divided into 2 groups, namely the negative control group (P1, given distilled water), the positive control group (P2; given paraquat 0.01 gr/kgBW [single dose intraperitoneal]). All samples of stored biological material were made for lung and kidney preparations. The lung condition was assessed using the American Thoracic Society criteria, and the kidneys were evaluated using the Mitchell criteria with the help of the ImageJ application. Data were analyzed using the Kruskal-Wallis test and the Mann-Whitney test. Results: The Kruskal-Wallis test showed a significant difference in lung damage scores between groups with a p-value of 0.01 (p <0.005). The results of the Kruskal-Wallis test of the kidneys showed substantial differences in glomerular and proximal tubular damage scores between groups with p values ​​of 0.004 and 0.009 (p <0.005). The results of the Mann-Whitney test also showed significant differences between groups P1 and P2 with a lung p value = 0.008 (p> 0.005) and kidney p = 0.009 (p > 0.005). Conclusion: In this study, it can be concluded that induction of paraquat 0.01 gr/kgBW causes changes in the histopathological appearance of the lungs and kidneys of white rats (Rattus norvegicus) in the form of lung and kidney damage as assessed by histopathological scores.

Paraquat disrupts the blood-brain barrier by increasing IL-6 expression and oxidative stress through the activation of PI3K/AKT signaling pathway.

Paraquat (PQ) is a frequently used herbicide with neurotoxic effects after acute or chronic exposure. Although in vitro evidence supports the PQ toxicity to dopamine cells, its in vivo effects (especially the chronic exposure) remain ambiguous. In this study, we investigated the effect of chronic PQ exposure on the blood-brain barrier (BBB) damage and the underlying mechanisms. Adult male Sprague Dawley rats and primary human brain microvascular endothelial (PHBME) cells were exposed to PQ as the animal and cell models. Evans Blue staining and hematoxylin & eosin staining were conducted to examine the BBB and brain tissue damages. The inflammatory cytokines were quantified via enzyme linked immunosorbent assay. The changes of PI3K/AKT signaling pathway were detected by western blot. PQ exposure can cause significant pathological lesions in the brain tissues and the BBB. IL-6 and reactive oxygen species levels were found to be significantly upregulated after PQ exposure in both the animal and cell models. PQ treatment could arrest the cell proliferation and migration in PHBME cells. PQ treatment promoted the phosphorylation of PI3K and AKT, and the application of PI3K inhibitor could attenuate PQ-induced IL-6 production, oxidative stress, BBB disruption, and brain tissue damage. Our study demonstrated that chronic PQ exposure could impair the BBB function and induce brain tissue damage. The overactivation of the PI3K/AKT pathway, consequent upregulation of IL-6 production, and increased oxidative stress appear to mediate the inflammatory damage resulting from PQ exposure.

A novel system for assessing paraquat toxicity using Desmodesmus maximus as a potential bio-indicator and deep learning-based approach

Microalgae play a crucial role as environmental indicators, offering valuable insights into ecosystem health and aiding in the assessment of water source contamination by toxins. In recent times, the presence of paraquat in water sources has become a grave concern due to its high toxicity and persistence. The detection of paraquat in natural water is of paramount importance for safeguarding water quality and public safety. Microalgae are invaluable bio-indicators for pollutant detection, but using small-sized microalgae according to OECD guidelines may not suit toxicity field combined with deep learning due to limitations. In this regard, this study proposes the use of Desmodesmus maximus as a potential bio-indicator, known for its larger cell size, surpassing Desmodesmus subspicatus, the reference strain specified by OECD guidelines. Exposure of D. maximus to 2 mg/L paraquat resulted in significant internal damage and loss of chlorophyll content, with a determined 72 h-EC50 of 0.25 mg/L. Accurate microalgae recognition typically requires time-consuming and inaccessible expert analysis. Therefore, this study explores deep learning techniques to enhance the efficiency and accuracy of microalgae toxicity testing. Deep convolutional neural networks (D-CNNs), including RetinaNet, YOLOv5, EfficientDet, and Faster R-CNN models, are compared for microalgae detection and differentiation. The analysis demonstrates the superiority of the Faster R-CNN model, achieving a remarkable mAP@0.5 value of 0.98 in multiclass conditions for identifying normal, empty, and toxified colonies. These findings underscore the considerable potential of deep learning techniques in advancing microalgae toxicity testing, thereby facilitating enhanced accessibility and cost-effectiveness in monitoring the environmental impact on water resources.

Integrated untargeted and targeted proteomics to unveil plasma prognostic markers for patients with acute paraquat poisoning: A pilot study

Paraquat (PQ) is a widely used but strongly toxic herbicide, which can induce multiple organ failure. The overall survival rate of the poisoned patients was only 54.4% due to lack of specific antidotes. Besides, the definite pathogenic mechanism of PQ is still not fully understood. In this pilot study, untargeted and targeted proteomics were integrated to explore the expression characteristics of plasma protein in PQ poisoned patients, and identify the differentially expressed proteins between survivors and non-survivors. A total of 494 plasma proteins were detected, and of which 47 were upregulated and 44 were downregulated in PQ poisoned patients compared to healthy controls. Among them, five differential plasma proteins (S100A9, S100A8, MB, ACTB and RAB11FIP3) were further validated by multiple reaction monitoring (MRM)-based targeted proteomic approach, and three of them (S100A9, S100A8 and ACTB) were confirmed to be correlated with PQ poisoning. Meanwhile, 84 dysregulated plasma proteins were identified in non-survivors compared with survivors. Moreover, targeted proteomic and ROC analysis suggested that ACTB had a good performance in predicting the prognosis of PQ poisoned patients. These findings highlighted the value of label-free and mass spectrometry-based proteomics in screening prognostic biomarkers of PQ poisoning and studying the mechanism of PQ toxicity.

Ecotoxicology of the herbicide paraquat: effects on wildlife and knowledge gaps.

Paraquat (PQ) is an organic herbicide introduced to the commercial market in 1962 and since linked to a variety of human health effects, including lung fibrosis, liver tumors, and Parkinson's disease. Although PQ is banned in the European Union, it is still frequently used in agricultural areas of the United States and Asia. The general mechanism of PQ's toxicity is the disruption of the redox cycle in cells. This mini-review summarizes our current understanding of PQ toxicity in non-target plants and animals. Among vertebrates, PQ sensitivity tends follow the pattern of fish > amphibians > mammals > birds. Aquatic plants are particularly vulnerable to PQ, with EC50 values ranging from ~28-280 μg/L. A number of convenient but non-specific biomarkers have been identified for non-target species, including the activities of antioxidant enzymes such as superoxide dismutase and catalase, histological changes in the gill structures of fish, and the upregulation of genes associated with the cytochrome p450 monooxygenase system. Significant literature gaps include a lack of data for environmentally realistic conditions (i.e., chronic, low concentration, multi-stressor), toxicity in reptiles, and population- and ecosystem-level effects. Although PQ is a useful herbicide, considering the many human and ecological health impacts, it may be time for regulators and the agricultural industry to reconsider its use.

Predicting mortality in paraquat poisoning through clinical findings, with a focus on pulmonary and cardiovascular system disorders

BackgroundParaquat, one of the most widely used herbicides, poses a significant risk of mortality through self-poisoning and subsequent multiple organ failure. The primary objective aimed to identify the factors associated with death in patients poisoned by paraquat.MethodsA cross-sectional retrospective review was conducted at a tertiary referral hospital over five years. Eligible patients presented with acute paraquat toxicity between 1 January 2016 and 31 December 2020. Medical records of 148 patients were reviewed.ResultsThe in-hospital fatality rate was found to be 21.8%. Multivariate analysis revealed that the amount of paraquat ingested and clinical presentations, particularly pulmonary and cardiovascular system disorders, were significantly associated with mortality.ConclusionOur study highlights that the amount of paraquat ingested, along with the presence of pulmonary and cardiovascular system disorders, can serve as prognostic indicators for mortality rates in cases of paraquat poisoning. These findings have important implications for physicians in predicting the prognosis and mortality of paraquat poisoning patients.Graphical

CDNF overexpression prevents motor-cognitive dysfunction by intrastriatal CPP-based delivery system in a Parkinson's disease animal model

Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compact (SNpc), and no effective treatment has yet been established to prevent PD. Neurotrophic factors, such as cerebral dopamine neurotrophic factor (CDNF), have shown a neuroprotective effect on dopaminergic neurons. Previously, we developed a cell-penetrating-peptide-based delivery system that includes Asn194Lys mutation in the rabies virus glycoprotein-9R peptide (mRVG9R), which demonstrated a higher delivery rate than the wild-type. In this study, using a mouse PD-like model, we evaluated the intrastriatal mRVG9R-KP-CDNF gene therapy through motor and cognitive tests and brain cell analysis. The mRVG9R-KP-CDNF complex was injected into the striatum on days 0 and 20. To induce the PD-like model, mice were intraperitoneally administered Paraquat (PQ) twice a week for 6weeks. Our findings demonstrate that mRVG9R-KP-CDNF gene therapy effectively protects brain cells from PQ toxicity and prevents motor and cognitive dysfunction in mice. We propose that the mRVG9R-KP-CDNF complex inhibits astrogliosis and microglia activation, safeguarding dopaminergic neurons and oligodendrocytes from PQ-induced damage. This study presents an efficient CDNF delivery system, protecting neurons and glia in the nigrostriatal pathway from PQ-induced damage, which is known to lead to motor and cognitive dysfunction in neurodegenerative diseases such as PD.

Predicting acute paraquat toxicity using physiologically based kinetic modelling incorporating in vitro active renal excretion via the OCT2 transporter

Including active renal excretion in physiologically based kinetic (PBK) models can improve their use in quantitative in vitro- in vivo extrapolation (QIVIVE) as a new approach methodology (NAM) for predicting the acute toxicity of organic cation transporter 2 (OCT2) substrates like paraquat (PQ). To realise this NAM, kinetic parameters Vmax and Km for in vitro OCT2 transport of PQ were obtained from the literature. Appropriate scaling factors were applied to translate the in vitro Vmax to an in vivo Vmax. in vitro cytotoxicity data were defined in the rat RLE-6TN and L2 cell lines and the human A549 cell line. The developed PQ PBK model was used to apply reverse dosimetry for QIVIVE translating the in vitro cytotoxicity concentration-response curves to predicted in vivo toxicity dose-response curves after which the lower and upper bound benchmark dose (BMD) for 50% lethality (BMDL50 and BMDU50) were derived by applying BMD analysis. Comparing the predictions to the in vivo reported LD50 values resulted in a conservative prediction for rat and a comparable prediction for human showing proof of principle on the inclusion of active renal excretion and prediction of PQ acute toxicity for the developed NAM.

Research progress of combination therapy of blood purification in the treatment of paraquat poisoning

Paraquat is a kind of herbicide effective in weeding, characterized by low cost and environmentally friendly property, which is widely used in agricultural weeding. However, the high toxicity of paraquat can cause damage to the lungs, liver, kidney, and other organs after oral intake. Worse still the patient will develop pulmonary fibrosis and will die of respiratory failure. At present, there is no specific detoxification drug for patients poisoned by paraquat. Based on the current therapeutic schedule, blood purification is considered to be the most effective method for the removal of paraquat-related toxins. However, there is a lot of controversy over the combined method. This paper expounds on the poisoning mechanism of paraquat and the advantages and disadvantages of different blood purification methods, aiming to find a specific scheme that can be applied to the clinic and improve the organ function and prognosis of patients.