Fractionated plasma separation and adsorption integrated with continuous veno-venous hemofiltration in patients with acute bipyridine herbicide poisoning.

OBJECTIVE: To evaluate the clinical efficacy and safety of fractionated plasma separation and adsorption combined with continuous veno-venous hemofiltration (FPSA-CVVH) treatment in patients with acute bipyridine herbicide poisoning. METHODS: A retrospective analysis of 18 patients with acute bipyridine herbicide poisoning was conducted, of which 9 patients were poisoned by diquat and 9 patients by paraquat. All patients underwent FPSA-CVVH treatment. The serum cytokine levels in pesticide-poisoned patients were assessed. The efficacy of FPSA-CVVH in eliminating cytokines, the 90-d survival rate of poisoned patients, and adverse reactions to the treatment were observed. RESULTS: Fourteen patients (77.8%) had acute kidney injuries and 10 (55.6%) had acute liver injuries. The serum cytokine levels of high mobility group protein B-1 (HMGB-1), interleukin-6 (IL-6), IL-8, interferon-inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1ß (MIP-1ß) were significantly elevated. A total of 41 FPSA-CVVH treatment sessions were administered. After a single 8-h FPSA-CVVH treatment, the decreases in HMGB-1, IL-6, IL-8, IP-10, MCP-1, and MIP-1ß were 66.0%, 63.5%, 73.3%, 63.7%, 53.9%, and 54.1%, respectively. During FPSA-CVVH treatment, one patient required a filter change due to coagulation in the plasma component separator, and one experienced a bleeding adverse reaction. The 90-d patient survival rate was 50%, with 4 patients with diquat poisoning and 5 patients with paraquat poisoning, and both liver and kidney functions were restored to normal. CONCLUSION: Cytokine storms may play a significant role in the progression of multiorgan dysfunction in patients with acute bipyridine herbicide poisoning. FPSA-CVVH can effectively reduce cytokine levels, increase the survival rate of patients with acute bipyridine herbicide poisoning, and decrease the incidence of adverse events.

Prognostic value of plasma diquat concentration in patients with acute oral diquat poisoning: a retrospective study.

Objectives: Diquat poisoning is an important public health and social security agency. This study aimed to develop a prognostic model and evaluate the prognostic value of plasma diquat concentration in patients with acute oral diquat poisoning, focusing on how its impact changes over time after poisoning. Methods: This was a retrospective cohort study using electronic healthcare reports from the Second Hospital of Hebei Medical University. The study sample included 80 patients with acute oral Diquat poisoning who were admitted to the hospital between January 2019 and May 2022. Time-to-event analyses were performed to assess the risk of all-cause mortality (30 days and 90 days), controlling for demographics, comorbidities, vital signs, and other laboratory measurements. The prognostic value of plasma DQ concentration on admission was assessed by computing the area under a time-dependent receiver operating characteristic curve (ROC). Results: Among the 80 patients, 29 (36.25%) patients died, and 51 (63.75%) patients survived in the hospital. Non-survivors had a median survival time (IQR) of 1.3(1.0) days and the longest survival time of 4.5 days after DQ poisoning. Compared with non-survivors, survivors had significantly lower amounts of ingestion, plasma DQ concentration on admission, lungs injury within 24 h after admission, liver injury within 24 h after admission, kidney injury within 24 h after admission, and CNS injury within 36 h after admission, higher APACHE II score and PSS within 24 h after admission (all p < 0.05). Plasma Diquat concentration at admission (HR = Exp (0.032-0.059 × ln (t))) and PSS within 24 h after admission (HR: 4.470, 95%CI: 1.604 ~ 12.452, p = 0.004) were independent prognostic factors in the time-dependent Cox regression model. Conclusion: Plasma DQ concentration at admission and PSS within 24 h after admission are independent prognostic factors for the in-hospital case fatality rate in patients with acute oral DQ poisoning. The prognostic value of plasma DQ concentration decreased with time.

Diquat causes mouse testis injury through inducing heme oxygenase-1-mediated ferroptosis in spermatogonia.

Diquat dibromide (DQ) is a globally used herbicide in agriculture, and its overuse poses an important public health issue, including male reproductive toxicity in mammals. However, the effects and molecular mechanisms of DQ on testes are limited. In vivo experiments, mice were intraperitoneally injected with 8 or 10 mg/kg/ day of DQ for 28 days. It has been found that heme oxygenase-1 (HO-1) mediates DQ-induced ferroptosis in mouse spermatogonia, thereby damaging testicular development and spermatogenesis. Histopathologically, we found that DQ exposure caused seminiferous tubule disorders, reduced germ cells, and increased sperm malformation, in mice. Reactive oxygen species (ROS) staining of frozen section and transmission electron microscopy (TEM) displayed DQ promoted ROS generation and mitochondrial morphology alterations in mouse testes, suggesting that DQ treatment induced testicular oxidative stress. Subsequent RNA-sequencing further showed that DQ treatment might trigger ferroptosis pathway, attributed to disturbed glutathione metabolism and iron homeostasis in spermatogonia cells in vitro. Consistently, results of western blotting, measurements of MDA and ferrous iron, and ROS staining confirmed that DQ increased oxidative stress and lipid peroxidation, and accelerated ferrous iron accumulation both in vitro and in vivo. Moreover, inhibition of ferroptosis by deferoxamine (DFO) markedly ameliorated DQ-induced cell death and dysfunction. By RNA-sequencing, we found that the expression of HO-1 was significantly upregulated in DQ-treated spermatogonia, while ZnPP (a specific inhibitor of HO-1) blocked spermatogonia ferroptosis by balancing intracellular iron homeostasis. In mice, administration of the ferroptosis inhibitor ferrostatin-1 effectively restored the increase of HO-1 levels in the spermatogonia, prevented spermatogonia death, and alleviated the spermatogenesis disorders induced by DQ. Overall, these findings suggest that HO-1 mediates DQ-induced spermatogonia ferroptosis in mouse testes, and targeting HO-1 may be an effective protective strategy against male reproductive disorders induced by pesticides in agriculture.

A SERS-based point-of-care testing approach for efficient determination of diquat and paraquat residues using a flexible silver flower-coated melamine sponge.

Diquat (DQ) and paraquat (PQ) residues in food are potential hazards to consumers' health. Point-of-care testing (POCT) of them remains challenging. Based on surface-enhanced Raman spectroscopy (SERS) technology, we developed a POCT strategy for DQ and PQ on apple surface and in apple juice. A point-of-use composite was fabricated using a piece of porous melamine sponge (MS) modified with silver nanoflowers (AgNFs), combining the specificity of the SERS fingerprint and the excellent adsorption capacity of MS. Using this dual-functional AgNFs@MS, the on-site determination of the DQ and PQ residues was completed within 3 min without pretreatment. Clear trends were observed between SERS intensity and logarithmic concentrations, with r values from 0.962 to 0.984. The limit of detection of DQ and PQ were 0.14-0.70 ppb in apple juice and on apple surface. This study provides a new point-of-use alternative for rapidly detecting DQ and PQ residues in nonlaboratory settings.

Mitochondria-associated endoplasmic reticulum membranes involve in oxidative stress-induced intestinal barrier injury and mitochondrial dysfunction under diquat exposing.

Many factors induced by environmental toxicants have made oxidative stress a risk factor for the intestinal barrier injury and growth restriction, which is serious health threat for human and livestock and induces significant economic loss. It is well-known that diquat-induced oxidative stress is implicated in the intestinal barrier injury. Although some studies have shown that mitochondria are the primary target organelle of diquat, the underlying mechanism remains incompletely understood. Recently, mitochondria-associated endoplasmic reticulum membranes (MAMs) have aroused increasing concerns among scholars, which participate in mitochondrial dynamics and signal transduction. In this study, we investigated whether MAMs involved in intestinal barrier injury and mitochondrial dysfunction induced by diquat-induced oxidative stress in piglets and porcine intestinal epithelial cells (IPEC-J2 cells). The results showed that diquat induced growth restriction and impaired intestinal barrier. The mitochondrial reactive oxygen species (ROS) was increased and mitochondrial membrane potential was decreased following diquat exposure. The ultrastructure of mitochondria and MAMs was also disturbed. Meanwhile, diquat upregulated endoplasmic reticulum stress marker protein and activated PERK pathway. Furthermore, loosening MAMs alleviated intestinal barrier injury, decrease of antioxidant enzyme activity and mitochondrial dysfunction induced by diquat in IPEC-J2 cells, while tightening MAMs exacerbated diquat-induced mitochondrial dysfunction. These results suggested that MAMs may be associated with the intestinal barrier injury and mitochondrial dysfunction induced by diquat in the jejunum of piglets.

[Diquat poisoning leads to ARDS: report of two cases].

Diquat (DQ) is a non-selective, foliage-applied herbicide that is known to cause liver and kidney damage, while the impact on the lungs is relatively mild. Current domestic and international reports on diquat poisoning primarily focus on liver and kidney injuries, with limited documentation of cases leading to acute respiratory distress syndrome (ARDS) and lung damage. This paper presents a retrospective analysis of two documented cases of diquat poisoning, both exhibiting ARDS. In both cases, the condition rapidly progressed upon the onset of ARDS despite aggressive treatment, ultimately resulting in the death of the patients.

Two cases of diquat poisoning in adolescent children.

Diquat (DQ) is among the most widely used herbicides, and its intake can cause severe systemic toxicity that manifests rapidly. The resultant symptoms can cause the dysfunction of a range of tissues and organs,. As there is no specific antidote for diquat poisoning and the efficacy of extant treatments is suboptimal, physicians must acquire a more comprehensive understanding of the most effective approaches to managing affected patients. Relative few studies have been published to date focused on diquat poisoning in pediatric patients. In this report, we compare two similar cases of juvenile diquat poisoning with dynamic changes in clinical manifestations, laboratory values, and imaging results. For the first time, the difference in whether to perform blood flow perfusion and the time difference of initiation of hemoperfusion had a clear clinical difference in the subsequent effects of diquat poisoning in children with diquat poisoning. Limited evidence is available regarding the efficacy of early hemoperfusion for diquat poisoning; however, the differences in clinical outcomes articulated here highlight the benefits of early and timely hemoperfusion therapy in the treatment of DQ toxicity in children, in conjunction with primary supportive care in the management of DQ poisoning in children.

Ratiometric emission of Tb(III)-functionalized Cd-based layered MOFs for portable visual detection of trace amounts of diquat in apples, potatoes and corn.

Diquat (DQ) is a typical bipyridine herbicide widely used to control weeds in fields and orchards. The severe toxicity of diquat poses a serious threat to the environment and human health. Metal-organic frameworks (MOFs) have received widespread attention due to their unique physical and chemical properties and applications in the detection of toxic and harmful substances. In this work, a two-dimensional (2D) Tb(III) functionalized MOF Tb(III)@1 (1 = [Cd(HTATB)(bimb)]n·H2O (Cd-MOF), H3TATB = 4,4',4″-triazine-2,4,6-tribenzoicacid, bimb = 1,4-bis((1H-imidazol-1-yl)methyl)benzene) has been prepared and characterized. Tb(III)@1 has excellent optical properties and high water and chemical stability. After the Tb(III) is fixed by the uncoordinated -COO- in the 1 framework, Tb(III)@1 emits the typical green fluorescence of the lanthanide ion Tb(III) through the "antenna effect". It is worth noting that Tb(III)@1 can be used as a dual emission fluorescence chemical sensor for the ratio fluorescence detection of pesticide DQ, exhibiting a relatively low detection limit of 0.06 nM and a wide detection range of 0-50 nM. After the addition of DQ, a rapid color change of Tb(III)@1 fluorescence from green to blue was observed due to the combined effects of IFE, FRET and dynamic quenching. Therefore, a simple test paper box has been designed for direct on-site determination of pesticide DQ. In addition, the developed sensor has been successfully applied to the detection of DQ in real samples (fruits a Yin-Xia Sun and Bo-Tao Ji contributed equally to this work and should be considered co-first authors.nd vegetables) with satisfactory results. The results indicate that the probe developed in this study has broad application prospects in both real sample detection and actual on-site testing.

Prognosis prediction of procalcitonin within 24 h for acute diquat poisoning.

BACKGROUND: To explore the predictive value of procalcitonin (PCT) within 24 h after poisoning for prognosis of acute diquat poisoning. METHODS: This retrospective study included acute diquat poisoning patients in the Nanyang City Hospital between May 2017 and July 2021. RESULTS: Among the 45 patients included, 27 survived. The maximum PCT value within 24 h after poisoning was significantly higher in the non-survival patients [9.65 (2.63, 22.77) vs. 0.15 (0.10, 0.50) µg/mL, P < 0.001] compared to the survival patients. The area under the ROC curve (AUC) indicated that the maximum PCT value within 24 h had a good predictive value (AUC = 0.905, 95% CI: 0.808-1.000) compared to ingested quantity (AUC = 0.879, 95% CI: 0.776-0.981), serum creatinine (AUC = 0.776, 95% CI: 0.640-0.912), or APACHE II score (AUC = 0.778, 95% CI: 0.631-0.925). The predictive value of maximum PCT value within 24 h was comparable with blood lactate (AUC = 0.904, 95%CI: 0.807-1.000). CONCLUSIONS: The maximum PCT value within 24 h after poisoning might be a good predictor for the prognosis of patients with acute diquat poisoning.

Simultaneous determination of diquat, paraquat, glufosinate, and glyphosate in plasma by liquid chromatography/tandem mass spectrometry: from method development to clinical application.

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.

Non-cytochrome P450 enzyme aldehyde oxidase is involved in the oxidative metabolic pathway of diquat and its detoxification effect.

Diquat (DQ) poisoning has garnered attention in recent years, primarily due to the rising incidence of cases worldwide, coupled with the absence of a viable antidote for its treatment. Despite the fact that diquat monopyridone (DQ-M) has been identified as a significant metabolite of DQ, the enzyme responsible for its formation remains unknown. In this study, we have identified aldehyde oxidase (AOX) as a vital enzyme involved in DQ oxidative metabolism. The metabolism of DQ to DQ-M was significantly inhibited by AOX inhibitors including raloxifene and hydralazine. The source of oxygen incorporated into DQ-M was proved to be from water through a H218O incubation experiment which further corroborated DQ-M formation via AOX metabolism. The product of DQ-M in vitro generated by fresh rat tissues co-incubation was consistent with its AOX expression. The result of the molecular docking analysis of DQ and AOX protein showed that DQ is capable of binding to AOX. Furthermore, the cytotoxicity of DQ was significantly higher than DQ-M at the same concentration tested in six cell types. This work is the first to uncover the involvement of aldehyde oxidase, a non-cytochrome P450 enzyme, in the oxidative metabolic pathway of diquat, thus providing a potential target for the development of detoxification treatment.

[Mechanism of intestinal injury induced by acute diquat poisoning in rats].

OBJECTIVE: To investigate the effects of diquat (DQ) on the expression of intestinal pyroptosis-related proteins and tight junction proteins in rats,and to analyze the role of pyroptosis in the intestinal injury of rats with acute DQ poisoning. METHODS: A total of 36 Wistar male rats were randomly divided into control group, and 3 hours, 12 hours, 36 hours and 3 days exposure groups, with 6 rats in each group. Each exposure group was given 1/2 median lethal dose (LD50) of 115.5 mg/kg DQ by one-time gavage. The control group was given the same amount of normal saline by gavage. The control group was anesthetized at 3 hours after DQ gavage to take jejunal tissues; each exposure group was anesthetized at 3 hours, 12 hours, 36 hours, and 3 days after DQ gavage to take jejunal tissues, respectively. The general conditions of the rats were recorded. The pathological changes of jejunum tissue were observed by hematoxylin-eosin (HE) staining. The expression of intestinal pyroptosis-related proteins [NOD-like receptor protein 3 (NLRP3), cysteine aspartate-specific protease 1 (caspase-1), Gasdemin D (GSDMD)] in the intestinal tissues was observed by immunohistochemical staining. Western blotting was used to detect the expression of intestinal pyroptosis-related proteins and intestinal tight junction proteins (Occludin and Claudin-1). RESULTS: Light microscopy showed that pathological changes occurred in jejunum tissue at the early stage of exposure (3 hours), and the injury was the most serious in the 12 hours exposure group, with a large number of inflammatory cells infiltrating in the tissue, and the damage was significantly reduced after 3 days exposure. Immunohistochemical results showed that NLRP3, caspase-1 and GSDMD were expressed in the jejunal mucosa of the control group and the exposure groups, and the positive cells in the control group were less expressed with light staining. The expression of the above proteins in the exposed group was increased significantly and the staining was deep. Western blotting results showed that compared with the control group, the expression of NLRP3 protein in jejunum tissues of all groups was increased, with the most significant increase in the 36 hours group (NLRP3/ß-actin: 1.47±0.06 vs. 0.43±0.14, P < 0.01). Compared with the control group, the expression of GSDMD protein in the 3 hours, 12 hours and 36 hours exposure groups increased, and the expression of GSDMD protein in the 3 hours and 12 hours exposure groups increased significantly (GSDMD/ß-actin: 1.04±0.40, 1.25±0.15 vs. 0.65±0.25, both P < 0.05). The expression of caspase-1 protein was increased in 36 hours exposure group compared with the control group (caspase-1/ß-actin: 1.44±0.34 vs. 0.98±0.19, P > 0.05). Compared with the control group, the expression of Occludin and Claudin-1 proteins in each exposure group decreased, and the expression of Occludin proteins was significantly decreased in the 3 hours, 12 hours, and 36 hours exposure groups decreased significantly (Occludin/ß-actin: 0.74±0.17, 0.91±0.20, 0.79±0.23 vs. 1.41±0.08, all P < 0.05). Although the protein expression of Claudin-1 decreased in each exposure group, the difference was not statistically significant. CONCLUSIONS: The intestinal injury caused by acute DQ poisoning may be related to the activation of pyroptosis pathway of small intestinal cells and the reduction of the density of intercellular junctions.

Curcumin alleviates cecal oxidative injury in diquat-induced broilers by regulating the Nrf2/ARE pathway and microflora.

This study evaluated the alleviative effect of curcumin (CUR) on the diquat (DQ)-induced cecal injury in broilers. A total of 320 one-day-old Cobb broilers were selected and randomly divided into 4 treatments, namely control, DQ, CUR 100, and CUR150 groups. The control and DQ groups were fed a basal diet, while the CUR 100 and CUR150 groups were fed the basal diet supplemented with 100 and 150 mg/kg CUR, respectively. Each group had 8 replicates, with 10 broilers per replicate. On day 21 of the experiment, 1 broiler was selected from each replicate and intraperitoneally injected 20 mg/kg body weight of DQ for DQ, CUR 100, and CUR 150 groups. Broilers in control group received equivalent volume of saline. Broilers were euthanized 48h postinjection for tissue sampling. The results showed that DQ injection could cause oxidative stress and inflammatory reactions in the cecum, affecting the fatty acid production and flora structure, thus leading to cecum damage. Compared with the DQ group, the activity of superoxide dismutase, the level of interleukin 10, acetic acid, and total volatile fatty, and the abundance of nuclear factor E2-related factor 2, copper and zinc superoxide dismutase and catalase mRNA in the cecal mucosa of broilers in the CUR group increased significantly (P < 0.05). However, the levels of malondialdehyd, reactive oxygen species, tumor necrosis factor-alpha, and the expression of cysteine-aspartic acid protease-3 and tumor necrosis factor-alpha decreased significantly (P < 0.05) in the CUR group. In addition, CUR treatment alleviated the damage to the cecum and restored the flora structure, and Lactobacillus and Lactobacillaceae promoted the alleviative effect of CUR on DQ. In summary, CUR could alleviate the cecal injury caused by DQ-induced oxidative damage and inflammatory reactions by regulating the Nrf2-ARE signaling pathway and intestinal flora, thus protecting the cecum.

Elucidating the mechanisms underlying astrocyte-microglia crosstalk in hippocampal neuroinflammation induced by acute diquat exposure.

The transition from paraquat (PQ) to diquat (DQ), both organic dication herbicides, in China has led to significant increases in the number of acute DQ poisoning cases. Case studies have shown that acute DQ poisoning resulted in injury to the central nervous system (CNS), but the mechanism underlying the injury remains to be explored. The present study aimed to investigate how DQ influenced purinergic signaling between astrocytes and microglia and whether extracellular ATP (eATP) was involved in promoting neuroinflammation induced by acute DQ toxicity through the activation of the P2X4/NLRP3 signaling pathway. We constructed a rat model of acute DQ toxicity to observe the pathological changes in hippocampal tissues after DQ exposure and measure the expression levels of IL-1ß and TNF-α in the hippocampal tissue. We also established an in vitro co-culture model of C6 astrocytes and BV-2 microglia using transwell chambers, measured the amount of eATP secreted into C6 astrocytes after DQ treatment, and assessed the inflammatory response and changes in the P2X4/NLRP3 signaling pathway in BV-2 microglia. The results showed that the neurons in the hippocampal tissue of rats exhibited loose arrangement, nuclear consolidation, and necrosis after DQ exposure, and IL-1ß and TNF-α levels were signification higher in the hippocampal tissue after DQ exposure. DQ exposure to the co-cultured cells induced an increase in ATP secretion from C6 astrocytes as well as a significant increase of P2X4, NLRP3, IL-1ß, and IL-18 expression in BV-2 microglia. In contrast, pretreatment of C6 astrocytes with apyrase (an ATP hydrolase) resulted in a significant decrease of P2X4, NLRP3, IL-1ß, and IL-18 expression in BV-2 microglia. Furthermore, inhibition of P2X4 expression in BV-2 microglia by transfection with si-P2X4 effectively reversed the increase of NLRP3, IL-1ß, and IL-18 in BV-2 microglia induced by DQ when co-cultured with C6 astrocytes. These results indicate that astrocytes can activate the P2X4/NLRP3 signaling pathway in microglia through the DQ-induced extracellular release of ATP to promote neuroinflammation in rat hippocampal tissue.

Simultaneous determination of water-soluble herbicides using hydrophilic interaction liquid chromatography-mass spectrometry.

PURPOSE: The analysis of water-soluble herbicides, including glyphosate (Glyp), glufosinate (Gluf), paraquat (PQ), and diquat (DQ), is time-consuming and expensive because they cannot be analyzed using general toxicological screening methods. Thus, this study aimed to develop a simple and rapid method to simultaneously analyze these compounds without any derivatization nor ion-pairing reagents. METHODS: The analytes were separated using hydrophilic interaction liquid chromatography and detected using tandem mass spectrometry. The developed method was applied to plant and biological samples assuming criminal damage and poisoning cases, respectively. RESULTS: All analytes were separated well and detected with good peak shapes. For plant samples, the herbicides were specifically detected from withered leaves using a simple extraction method. For biological samples, quantitative analysis was successfully validated, and the limit of quantification values of Glyp and Gluf were 0.2 µg/mL, and those of PQ and DQ were 1 ng/mL. CONCLUSION: The developed method had sufficient performance for practical forensic applications including poisoning cases and malicious uses to damage commercial crops.

Clinical characteristics of survivors versus non-survivors after acute diquat poisoning: a comparative study.

The aim of this study was to compare the clinical characteristics between survivors and non-survivors after acute diquat (DQ) poisoning. Patients treated in the Emergency Department of Fu Yang People's Hospital for DQ poisoning between January 2018 and February 2022 were enrolled in this retrospective comparative study. A total of 65 patients were collected, including 36 males (55.4%) and 29 females (44.6%). There were 34 survivors (52.3%), and 31 non-survivors (47.7%). Patients in the non-survivor group were significantly older (P = 0.003), received a higher dose of DQ before admission (P < 0.001), had more severe organ damage (P < 0.001), lower respiration rate (P < 0.001) and enema (P = 0.009), lower GCS score (P = 0.038), and higher SIRS score (P = 0.018) and APACHE-II score (P < 0.001) than patients in the survivor group. Additionally, biochemical indicators after admission between survivors and non-survivors were significantly different (all P < 0.05). Multivariate logistic regression analysis showed that respiratory failure (P = 0.021), the dose of DQ (P = 0.022), respiratory rate (P = 0.007), and highest alanine transaminase (ALT) level after admission (P = 0.030) were independent risk factors for acute DQ-induced death. These data suggest that non-survivors with acute DQ poisoning are more likely to suffer from respiratory failure, have higher respiratory rate and ALT after admission, and are exposed higher doses of DQ before admission than survivors.

Melatonin increased antioxidant capacity to ameliorate growth retardation and intestinal epithelial barrier dysfunction in diquat-challenged piglets.

BACKGROUND: Diquat is a common environmental pollutant, which can cause oxidative stress in humans and animals. Diquat exposure causes growth retardation and intestinal damage. Therefore, this study was performed to investigate the effects of melatonin on diquat-challenged piglets. RESULTS: Dietary supplementation with 2 mg kg-1 melatonin significantly increased the average daily gain and feed conversion rate in piglets. Melatonin increased antioxidant capacity, and improved intestinal epithelial barrier function of duodenum and jejunum in piglets. Moreover, melatonin was found to regulated the expression of immune and antioxidant-related genes. Melatonin also alleviated diquat-induced growth retardation and anorexia in diquat-challenged piglets. It also increased antioxidant capacity, and ameliorated diquat-induced intestinal epithelial barrier injury. Melatonin also regulated the expression of MnSOD and immuner-elated genes in intestinal. CONCLUSION: Dietary supplementation with 2 mg kg-1 melatonin increased antioxidant capacity to ameliorate diquat-induced oxidative stress, alleviate intestinal epithelial barrier injury, and increase growth performance in weaned piglets. © 2023 Society of Chemical Industry.

Development of LC-MS/MS analytical method for the rapid determination of Diquat in water and beverages.

This study aimed to develop simple, fast, and sensitive methods for the determination of diquat (DQ) in various matrices such as water and beverages. For water, direct injection was tested first, however, the sensitivity of the incurred samples were too low and couldn't possibly achieve the targeted limit of quantification. Hence, dilution with "weaker" injection solvents were tested, and the final conditions involved the dilution of water with acetonitrile (0.4 % ammonium hydroxide) which increased the sensitivity by more than ten times. Nevertheless, the beverages samples needed further treatment to achieve acceptable spiked recovery. The final conditions involved extraction using the aforementioned solvent, followed by heating and partitioning. Both of the methods satisfied the validation requirements, with an average recovery ranging from 85.9 to115 % and associated relative standard deviation (RSD %) within the range 3-8. Further applications on real samples were done to test the levels of contamination.

Autophagy mediated FTH1 degradation activates gasdermin E dependent pyroptosis contributing to diquat induced kidney injury.

Acute kidney injury (AKI) induced by diquat (DQ) progresses rapidly, leading to high mortality, and there is no specific antidote for this chemical. Our limited knowledge of the pathogenic toxicological mechanisms of DQ has hindered the development of treatments against DQ poisoning. Pyroptosis is a form of programmed cell death and was recently identified as a novel molecular mechanism of drug-induced AKI. To explore the role of pyroptosis in HK-2 cells exposed to DQ, the plasma membrane damage of the cells was detected by LDH release assay. Western blot was performed to detect the cleavage of GSDME. Proteomics analysis was performed to explore the mechanism of DQ induced nephrotoxicity. FerroOrange probe was used to measure the intracellular Fe2+ levels. Herein, we show that DQ induces pyroptosis in HK-2 cells. Mechanistically, DQ induces the accumulation of mitochondrial ROS and initiates the cleavage of gasdermin E (GSDME) in an intrinsic mitochondrial pathway. Knockout of GSDME attenuated DQ-induced cell death. Further analysis revealed that loss of FTH1 induces Fe2+ accumulation, contributing to DQ-induced pyroptosis. Knockdown LC3B could help restore the expression of FTH1 and improve cell viability. Moreover, we found DFO, an iron chelator, could reduce cellular Fe2+ levels and inhibit pyroptosis. Collectively, these findings suggest an unrecognized mechanism for GSDME-dependent pyroptosis in DQ-induced AKI.