Explore the vast range of titles available.

Diquat (DQ) is a potent, non-selective herbicide which can result in severe poisoning and a high mortality if ingested accidentally or intentionally. Diquat poisoning can cause extensive damage to multiple organs, including the intestines, liver, kidneys, brain, and other organs. As there are no specific antidotes available for DQ poisoning, the current therapeutic strategies are essentially restricted to blood purification therapy and supportive care. Numerous studies on the molecular mechanisms and potential therapeutic agents have been conducted over the past few decades. However, there has been no comprehensive summary or analysis of these findings. This review extensively investigates the molecular mechanisms underlying DQ-induced organ injury, with a particular focus on the major signaling pathways. In addition, searches were conducted in PubMed and Web of Science using the following search terms: \"diquat\"[tiab] OR \"diquat\"[MeSH Terms]. A total of 166 eligible papers published over the past 35 years were selected. Consequently, more than seventy potential therapeutic agents with protective effects against DQ-induced toxicity are summarized and analyzed. In the future, it will be essential to conduct preclinical research and clinical trials to extrapolate these findings to humans. Graphical Abstract

This study aimed to investigate the protective effects of dietary glutamate and aspartate supplementations on diquat-induced oxidative stress in piglets. Diquat injection significantly reduced growth performance, including body weight, average daily weight gain, and feed intake (P<0.05). Meanwhile, diquat administration induced oxidative stress evidenced by the decreased serum nitric oxide (NO) and elevated malondialdeyhde (MDA) concentration (P<0.05). Furthermore, diquat-induced oxidative stress disrupted intestinal absorption system and decreased serum threonine, serine, and glycine levels. Dietary supplementation with glutamate improved final body weight, antioxidant system, and expressions of amino acids transporters and enhanced serum glutamate concentration compared with diquat group (P<0.05). While aspartate failed to alleviate diquat-induced oxidative stress, growth depression, and dysfunction of nutrients absorption except for liver relative weight. In conclusion, dietary supplementation with glutamate confers beneficial effects on diquat-induced oxidative stress in piglets, while aspartate exhibits little effects.

Purpose This study aimed to develop and validate an ultraperformance liquid chromatography–tandem mass spectrometry to simultaneously determine diquat (DQ) and its two primary metabolites in rat plasma and its application to the toxicokinetic study. Method The chromatographic separation of DQ and its two primary metabolites was performed with hydrophilic interaction chromatography column by adding formic acid and ammonium acetate in mobile phase in stepwise elution mode. DQ and its two primary metabolites were detected by liquid chromatography–tandem mass spectrometry in positive mode. Results The lower limit of quantification ranging from 0.3 to 3.0 ng/mL for DQ and its two primary metabolites was achieved by using only 50 μL of rat plasma. The maximum concentration ( C max ) was 977 ng/mL, half-life ( t 1/2 ) was 13.1 h, and area under the plasma concentration–time curve (AUC 0–t ) was 2770 h*ng/mL for DQ, C max was 47.1 ng/mL, t 1/2 was 25.1 h, and AUC 0–t was 180 h·ng/mL for diquat monopyridone (DQ-M) and C max was 246 ng/mL, t 1/2 was 8.2 h, and AUC 0–t was 2430 h·ng/mL for diquat dipyridone (DQ-D), respectively. Conclusions The validated method was shown to be suitable for simultaneous determination of diquat and its two primary metabolites in rat plasma. This study is the first to study the toxicokinetics of DQ and its two primary metabolites.

The aim of this study was to develop and validate predictive models for assessing the risk of death in patients with acute diquat (DQ) poisoning using innovative machine learning techniques. Additionally, predictive models were evaluated through the application of SHapley Additive ExPlanations (SHAP). A total of 201 consecutive patients from the emergency departments of the First Hospital and Shengjing Hospital of China Medical University admitted for deliberate oral intake of DQ from February 2018 to August 2023 were analysed. The initial clinical data of the patients with acute DQ poisoning were collected. Machine learning methods such as logistic regression, random forest, support vector machine (SVM), and gradient boosting were applied to build the prediction models. The whole sample was split into a training set and a test set at a ratio of 8:2. The performances of these models were assessed in terms of discrimination, calibration, and clinical decision curve analysis (DCA). We also used the SHAP interpretation tool to provide an intuitive explanation of the risk of death in patients with DQ poisoning. Logistic regression, random forest, SVM, and gradient boosting models were established, and the areas under the receiver operating characteristic curves (AUCs) were 0.91, 0.98, 0.96 and 0.94, respectively. The net benefits were similar across all four models. The four machine learning models can be reliable tools for predicting death risk in patients with acute DQ poisoning. Their combination with SHAP provides explanations for individualized risk prediction, increasing the model transparency.

Ellagic acid (EA) is the main constituent found in pomegranate rind, which has anti-inflammatory and antioxidant effects. However, whether EA can alleviate diquat-induced oxidative stress is still unknown. Here, the effects and mechanisms of EA on jejunum oxidative stress induced by diquat was investigated. Oxidative stress was induced in mice by administrating diquat (25 mg/kg body weight) followed by treatment with 100 mg/kg body weight EA for 5 days. Results showed that oral administration of EA significantly ameliorated diquat-induced weight loss and oxidative stress (p < 0.05) evidenced by reduced ROS production in the jejunum. Furthermore, EA up-regulated the mRNA expression of the antioxidant enzymes (Nrf2, GPX1 and HO-1) when mice were challenged with diquat, compared with the diquat group (p < 0.05). Importantly, pharmacological inhibition of Nrf2 by ML385 counteracted the EA-mediated alleviation of jejunum oxidative stress, as evidence by body weight and ROS production. Also, immunohistochemistry staining confirmed the markedly decreased jejunal Nrf2 expression. The up-regulated effect on NQO1 and HO-1 mRNA expression induced by EA was diminished in mice treated with ML385 (p < 0.05). Together, our results demonstrated that therapeutic and preventative EA treatment was effective in reducing weight loss and oxidative stress induced by diquat through the Nrf2 mediated signaling pathway.

Diquat (DQ), paraquat (PQ), glufosinate (GLU), and glyphosate (GLYP) are commonly used herbicides that have been confirmed to be toxic to humans. Rapid and accurate measurements of these toxicants in clinical practice are beneficial for the correct diagnosis and timely treatment of herbicide-poisoned patients. The present study aimed to establish an efficient, convenient, and reliable method to achieve the simultaneous quantification of DQ, PQ, GLU, and GLYP in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS) without using derivatization or ion-pairing reagents. DQ, PQ, GLU, and GLYP were extracted by the rapid protein precipitation and liquid-liquid extraction method and then separated and detected by LC-MS/MS. Subsequently, linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, extraction recovery, matrix effect, dilution integrity, and stability were evaluated to validate the method based on the FDA criteria. Finally, the validated method was applied to real plasma samples collected from 166 Chinese patients with herbicide poisoning. The results showed satisfactory linearity with low LOD (1 ng/mL for DQ and PQ, 5 ng/mL for GLU, and 10 ng/mL for GLYP, respectively) and low LOQ (5 ng/mL for DQ and PQ, 25 ng/mL for GLU and GLYP, respectively). In addition, the precision, accuracy, extraction recovery, and stability of the method were acceptable. The matrix effect was not observed in the analyzed samples. Moreover, the developed method was successfully applied to determine the target compounds in real plasma samples. These data provided reliable evidence for the application of this LC-MS/MS method for clinical poisoning detection.

This study aimed to investigate whether enema is associated with nervous system injury caused by diquat poisoning using a population-based case-control analysis. Medical records of patients with acute diquat poisoning admitted to the hospital from January 2018 to January 2024 were retrospectively collected. Central nervous system injury symptoms following diquat poisoning defined the case group, while the control group were matched 1:2 on population-based without nervous system injury in diquat poisoning patients. Conditional logistic regression models were used for analysis. We identified 101 diquat poisoning patients with nervous system injury and selected 202 diquat poisoning patients without nervous system injury. Diquat poisoning patients performed 2 and ≧ 3 enemas had ORs of nervous system injury of 3.084 (95% CI 1.230, 7.734) and 4.693 (95% CI 1.408, 15.645) compared with diquat poisoning patients with no enema, respectively. Further analyses were performed in various age subgroups. The ORs of conducting 2 and ≧ 3 enemas were dramatically higher among case group than control group in subgroup aged ≧ 60 years old (OR  10.184, 14.982 respectively). We concluded that enema may be associated with an increased risk of nervous system injury caused by DQ poisoning, particularly among the elderly.

Diquat (DQ) is a nonselective bipyridine herbicide with a structure resembling paraquat (PQ). In recent years, the utilization of DQ as a substitute for PQ has grown, leading to an increase in DQ poisoning cases. While the toxicity mechanism of DQ remains unclear, it is primarily attributed to the intracellular generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) through the process of reduction oxidation. This results in oxidative stress, leading to a cascade of clinical symptoms. Notably, recent reports on DQ poisoning have highlighted a concerning trend: an upsurge in cases involving neurological damage caused by DQ poisoning. These patients often present with severe illness and a high mortality rate, with no effective treatment available thus far. Imaging findings from these cases have shown that neurological damage tends to concentrate on the brainstem. However, the specific mechanisms behind this poisoning remain unclear, and no specific antidote exists. This review summarizes the research progress on DQ poisoning and explores potential mechanisms. By shedding light on the nerve damage associated with DQ poisoning, we hope to raise awareness, propose new avenues for investigating the mechanisms of DQ poisoning, and lay the groundwork for the development of treatment strategies for DQ poisoning. Trial registration number: 2024PS174K.

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.

Diquat is a nonselective herbicide that is used as a contact and preharvest desiccant to control terrestrial and aquatic vegetation. Increasing numbers of cases of diquat poisoning have recently been reported. Organs commonly affected by diquat poisoning include the kidney, liver, and lung. Neurological involvement of diquat poisoning is relatively rare. A 21-year-old man ingested 100 mL of diquat (20 g/100 mL) 5 hours before admission. Fifteen minutes after ingestion, he developed nausea and vomiting. The patient was sent to the emergency intensive care unit, and gastric lavage was performed. Continuous renal replacement therapy and continuous venovenous hemodiafiltration with hemoperfusion were performed, and methylprednisolone was administered. Five days after admission, the patient developed disturbance of consciousness and positive bilateral Babinski signs. Head computed tomography demonstrated hypodensity in the pons. At 11 days after admission, brain magnetic resonance imaging showed acute pontine demyelination. At 15 days after admission, the patient died of multiple organ dysfunction syndrome. We encountered a case of diquat poisoning with central pontine myelinolysis and acute kidney injury. This case highlights the clinical value of neuroimaging examination for early diagnosis of central pontine myelinolysis.