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.

[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.

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.

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.

Magnolol supplementation alleviates diquat-induced oxidative stress via PI3K-Akt in broiler chickens.

This experiment was conducted to investigate the effects of magnolol on the oxidative parameters and jejunum injury induced by diquat in broiler chickens. This test adopts a 2 × 2 factors design, a total of 288 one-day-old male AA broiler chicks randomly allocated to four groups, consisting of six replicates of 12 birds each, which was then denoted as CON group, diquat (DIQ) group (16 mg/kg BW diquat was injected into birds at the age of 21 days), magnolol (MAG) group (basic bird diet supplemented with 300 mg/kg magnolol), and MAG + DIQ group. At 21 days of age, broilers in the DIQ group and the MAG + DIQ group were intraperitoneally injected with 16 mg/kg BW diquat. Results showed that diet supplementing with MAG could alleviate the decrease of ADG to a certain extent after exposure to DIQ. Addition of magnolol to the diet alleviated the decrease of ADG during injection, antioxidant enzymes, and gene expression and increased the markers of oxidative damage induced by diquat induction. Magnolol supplement reversed the increase of apoptotic cells in the diquat-induced chicken jejunum. RNA sequencing showed that PI3K-Akt, calcium, and NF-kappa B signaling pathways were the main enrichment pathways between the DIQ group and the MAG + DIQ group. Our findings revealed that magnolol may improve antioxidant enzyme activity and expression of related genes through the PI3K-Akt pathway to alleviate oxidative stress.

Clinical and pathological characteristics of diquat poisoning-related acute kidney injury.

Objectives: Diquat has replaced paraquat in agricultural areas as a herbicide but has led to extensive poisoning. Unlike paraquat, which targets the lungs, diquat primarily targets the kidneys. Autopsies and animal experiments suggest that interstitial kidney damage is the most critical renal lesion. Diquat is a nonselective chemical widely used for terrestrial and aquatic plants after the ban on paraquat. Although diquat is known to affect the kidneys mainly, no study has reported renal biopsy in patients with diquat poisoning.Methods: We investigated the histopathologic feature in a young man with diquat poisoning who developed acute kidney injury by renal biopsy.Results: Autopsy and animal experiments suggest that interstitial kidney inflammation is the most critical renal lesion. Surprisingly, our results showed that lipid degeneration and acute tubular injury with limited interstitial inflammation were the dominant histologic findings in this patient. Conclusions: Based on a renal biopsy, this was the first study describing the characteristics of the kidney affected by diquat poisoning. Our findings might provide information for managing patients who develop AKI due to diquat poisoning.

Clinical and pathological characteristics of acute kidney injury caused by diquat poisoning.

Introduction: Diquat poisoning leads to kidney injury, hepatotoxicity, rhabdomyolysis, gastrointestinal hemorrhage, and respiratory failure. Diquat has high mortality and no specific antidote. The pathology of acute kidney injury caused by diquat poisoning has been mainly investigated in animal studies and autopsies, and typically shows renal tubular necrosis. To our knowledge, antemortem renal biopsy has not been reported in humans.Case reports: Two males and one female presented following deliberate diquat self-poisoning. Their main clinical manifestations were abdominal pain, nausea, and emesis. All developed acute kidney injury. Kidney biopsy was performed in two cases which showed acute tubular necrosis with renal interstitial edema and multifocal inflammatory cell infiltration. Treatments given included gastric lavage, catharsis, early hemoperfusion combined with continuous kidney replacement therapy or hemodialysis, administration of glucocorticoids, and antioxidant therapy. All patients survived.Discussion: Despite potentially lethal ingestions three patients survived oral diquat poisoning with intensive supportive care. No clear relationship can be made between any of the therapies given and patient outcome.Conclusions: Kidney biopsy in these patients confirmed proximal renal tubular injury was the major pathological finding although interstitial injury was also present. The role of therapies that address renal pathology requires further study.

Study on the therapeutic effect of glucocorticoids on acute kidney injury in rats exposed to diquat.

AIMS: To preliminarily explore, whether glucocorticoids have a therapeutic effect on diquat-induced acute kidney injury in rats. METHOD: 150 Wistar rats were randomly divided into six groups: exposure model group (DQ group), dexamethasone control group (GC group), blank control group (Ctrl group), dexamethasone 2.1 mg/kg dose group (DQ+L-GC group), dexamethasone 4.2 mg/kg dose group (DQ+M-GC group), and dexamethasone 8.4 mg/kg dose group (DQ+H-GC group), with 25 rats in each group. Each group was further divided into five subgroups, 24 h, 3 d, 7 d, 14 d, and 21 d after exposure, according to the feeding time and the course of treatment, with five animals in each subgroup. The rats in DQ, DQ+L-GC, DQ+M-GC, and DQ+H-GC groups were administered 115.5 mg/kg diquat by gavage, respectively. Moreover, 30 min after gavage, rats in DQ+L-GC group, DQ+M-GC group, DQ+H-GC group and GC group were intragastric administered dexamethasone 2.1 mg/kg, 4.2 mg/kg, 8.4 mg/kg and 8.4 mg/kg, respectively. After 7 days, the intraperitoneal injection of dexamethasone was changed to 6.3 mg/kg prednisone by intragastric administration. Subsequently, 7 days later, it was changed to 3.15 mg/kg prednisone by intragastric administration until the end of the experiment on 21 days. After the start of the experiment, changes in the conditions of the rats in each group were observed at a fixed time every day, changes in the body weight of the rats were monitored at the same time, and the death of the rats was recorded at 24 h, 3 d, 7 d, 14 d, and 21 d after exposure. The rats were sacrificed by an intraperitoneal injection of 100 mg/kg sodium pentobarbital overdose. Blood was collected by puncture of the inferior vena cava, used to determine Cr and BUN. The upper segment of the left kidney was collected for histopathological examination. Elisa was used to detect neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in the lower segment of left kidney. TLR4, Myd88, and NF-κB were detected in the right kidney. RESULTS: (1) After exposure, most rats in DQ group, DQ+L-GC group, DQ+M-GC group and DQ+H-GC group showed shortness of breath, oliguria, diarrhea, yellow hair and other symptoms. No symptoms and related signs were observed in Ctrl group and GC group. (2) The weight of rats in the Ctrl group and the GC group increased slowly during the test. the body weight of the rats in the DQ, DQ+L-GC, DQ+M-GC, and DQ+H-GC groups continued to decrease after self-infection. Body weight dropped to the lowest point at approximately 7 d, and gradually increased from 7 d to 21 d. (3) A small amount of capillary congestion in the medulla was observed after 7 days in the GC group. The DQ group showed tubular atrophy, edema of the epithelial cells, and over time, the tubules were seen dilated and became irregular in shape; large amount of capillary congestion was also observed in the renal cortex and medulla. The renal injury in the DQ+L-GC group was less than that in the DQ group. DQ+H-GC group had no obvious injury before 7 d, but more renal tubules were seen in the DQ+H-GC group from 7 d to 14 d. (4) Compared with the DQ group, there was no difference before 14 d, and at 14 d-21 d, DQ+L-GC group, DQ+M-GC group, DQ+H-GC group all had different degrees of decline. NGAL content: Compared with the DQ group, the content of NGAL and KIM-1 in kidney tissue of the DQ+L-GC, DQ+M-GC, and DQ+H-GC groups decreased compared with the DQ group at each time node. (5) Compared with the Ctrl group, the expression of TNF-α, TLR4, MyD88, NF-κB in the DQ, DQ+L-GC, DQ+M-GC, and DQ+H-GC groups at each time node increased in the renal tissue. The content of TNF-α, TLR4, MyD88, NF-κB in kidney tissue of the DQ+L-GC, DQ+M-GC, and DQ+H-GC groups at each time node was lower than that in the DQ group. CONCLUSION: (1) Diquat can cause kidney damage in rats, mainly manifested as renal tubular atrophy, epithelial cell edema, capillary congestion and dilation, and the renal function damage indicators have been improved to varying degrees. (2) Glucocorticoids have therapeutic effects on acute kidney injury in rats exposed to diquat. During the treatment, the efficacy of glucocorticoids did not increase with increasing doses after reaching a dose of 4.2 mg/kg. (3) TLR4 receptor-mediated TLR4/Myd88/NF-κB signaling pathway is involved in the inflammatory response of acute kidney injury in diquat poisoning rats. Glucocorticoids can inhibit the inflammatory response, thereby affecting the expression of TLR4/Myd88/NF-κB signaling pathway-related proteins.

Supramolecular Fluorescence Sensor Array Based on Cucurbit[8]uril Complexes Used for the Detection of Multiplex Quaternary Ammonium Pesticides.

The simultaneous detection of multiple quaternary ammonium pesticides (QAPs) in water is a challenge due to their high solubility in water and similar structures. In this paper, we have developed a quadruple-channel supramolecular fluorescence sensor array for the simultaneous analysis of five QAPs, including paraquat (PQ), diquat (DQ), difenzoquat (DFQ), mepiquat (MQ), and chlormequat (CQ). Not only were QAP samples of different concentrations (10, 50, and 300 µM) in water distinguished with 100% accuracy but also single QAP and binary QAP mixed samples (DFQ-DQ) were sensitively quantified. Our experimental interference study confirmed that the developed array has good anti-interference ability. The array can quickly identify five QAPs in river and tap water samples. In addition, it also qualitatively detected QAP residues in Chinese cabbage and wheat seedlings extract. This array has rich output signals, low cost, easy preparation, and simple technology, demonstrating great potential in environmental analysis.

Understanding the risk of using herbicides for tree root removal into wastewater treatment plant performance.

Adding herbicides to sewer lines, a common practice for controlling root intrusion in sewer pipes, may adversely impact downstream wastewater treatment by inhibiting nitrification and denitrification performance. This study investigated the effects of herbicides, namely diquat, triclopyr, and 2-methyl-4-chlorophenoxyacetic acid (MCPA)-dicamba, on these processes. Various parameters were monitored, including oxygen uptake rate (OUR), nutrients (NH3-N, TP, NO3-N, and NO2-N), chemical oxygen demand (COD), and herbicide concentrations. It was found that nitrification was not affected by OUR in the presence of each herbicide at various concentrations (1, 10, and 100 mg L-1). Additionally, MCPA-dicamba at various concentrations demonstrated minimal inhibition in the nitrification process compared to diquat and triclopyr. COD consumption was not affected by the presence of these herbicides. However, triclopyr significantly inhibited NO3-N formation in the denitrification process at various concentrations. Similar to nitrification process, both COD consumption and herbicide reduction concentration were not affected by the presence of herbicides during the denitrification process. Adenosine triphosphate measurements showed minimal impact on nitrification and denitrification processes when herbicides were present in the solution up to a concentration of 10 mg L-1. Tree root kill efficiency experiments were performed on Acacia melanoxylon. Considering the performance on nitrification and denitrification process, diquat emerged as the best herbicide option (concentration of 10 mg L-1), with a 91.24% root kill efficiency.

Dietary glutathione supplementation attenuates oxidative stress and improves intestinal barrier in diquat-treated weaned piglets.

The aim of this study was to investigate the protective effects of glutathione (GSH) against oxidative stress and intestinal barrier disruption caused by diquat (an oxidative stress inducer) in weaned piglets. Twenty-four piglets were randomly assigned to four treatments with six pigs per treatment for an 18-d trial. Treatments were basal diet, basal diet + diquat challenge, 50 mg/kg GSH diets + diquat challenge and 100 mg/kg GSH diets + diquat challenge. On day 15, piglets in basal diet group and diquat-challenged groups were intraperitoneally injected with sterile saline and diquat at 10 mg/kg body weight, respectively. The results showed that GSH supplementation improved growth performance of diquat-injected piglets from days 15 to 18 (p < 0.05), especially at a dose of 100 mg/kg GSH. Meanwhile, diquat also caused oxidative stress and intestinal barrier damage in piglets. However, GSH supplementation enhanced the antioxidant capacity of serum and jejunum, as evidenced by the increase in GSH content and total superoxide dismutase activities and the decrease in 8-hydroxy-2'-deoxyguanosine concentrations (p < 0.05). GSH also up-regulated the mRNA expressions of intestinal tight junction protein (zonula occludens 1, ZO1; occludin, OCLN; claudin-1, CLDN1) and mitochondrial biogenesis and function (peroxisome proliferator-activated receptor-gamma coactivator-1 alpha, PGC1α; mitochondrial transcription factor A, TFAM; cytochrome c, CYCS), compared with diquat-challenged piglets in basal diet (p < 0.05). Thus, the study demonstrates that GSH protects piglets from oxidative stress caused by diquat and 100 mg/kg GSH has a better protective role.

Metabolomics profile of plasma in acute diquat-poisoned patients using gas chromatography-mass spectrometry.

Diquat (DQ) has been confirmed to be toxic to humans and responsible for severe health impairment. While to date, very little is known about the toxicological mechanisms of DQ. Thus, investigations to discover the toxic targets and potential biomarkers of DQ poisoning are urgently needed. In this study, a metabolic profiling analysis was conducted to reveal the changes of metabolites of plasma and find out the potential biomarkers of DQ intoxication by GC-MS. First, multivariate statistical analysis demonstrated that acute DQ poisoning can lead to metabolomic changes in human plasma. Then, metabolomics studies showed that 31 of the identified metabolites were significantly altered by DQ. Pathway analysis indicated that three primarily metabolic pathways including phenylalanine, tyrosine and tryptophan biosynthesis, taurine and hypotaurine metabolism, and phenylalanine metabolism were affected by DQ, resulting in the perturbations of phenylalanine, tyrosine, taurine, and cysteine. Finally, the results of receiver operating characteristic analysis showed the above four metabolites could be used as reliable tools for the diagnosis and severity assessments of DQ intoxication. These data provided the theoretical basis for basic research to understand the potential mechanisms of DQ poisoning, and also identified the desirable biomarkers with great potential for clinical applications.

Effects of dietary supplementation with chlorogenic acid on growth performance, antioxidant capacity, and hepatic inflammation in broiler chickens subjected to diquat-induced oxidative stress.

This study was conducted to investigate the protective effects of chlorogenic acid (CGA) on broilers subjected to (DQ)-induced oxidative stress. In experiment 1, one hundred and ninety-two male one-day-old Ross 308 broiler chicks were distributed into 4 groups and fed a basal diet supplemented with 0, 250, 500, or 1,000 mg/kg CGA for 21 d. In experiment 2, an equivalent number of male one-day-old chicks were allocated to 4 treatments for a 21-d trial: 1) Control group, normal birds fed a basal diet; 2) DQ group, DQ-challenged birds fed a basal diet; and 3) and 4) CGA-treated groups: DQ-challenged birds fed a basal diet supplemented with 500 or 1,000 mg/kg CGA. The intraperitoneal DQ challenge was performed at 20 d. In experiment 1, CGA administration linearly increased 21-d body weight, and weight gain and feed intake during 1 to 21 d (P < 0.05). CGA linearly and/or quadratically increased total antioxidant capacity, catalase, superoxide dismutase, and glutathione peroxidase activities, elevated glutathione level, and reduced malondialdehyde accumulation in serum, liver, and/or jejunum (P < 0.05). In experiment 2, compared with the control group, DQ challenge reduced body weight ratio (P < 0.05), which was reversed by CGA administration (P < 0.05). DQ challenge increased serum total protein level, aspartate aminotransferase activity, and total bilirubin concentration (P < 0.05), which were normalized when supplementing 500 mg/kg and/or 1,000 mg/kg CGA (P < 0.05). DQ administration elevated hepatic interleukin-1ß, tumor necrosis factor-α, and interleukin-6 levels (P < 0.05), and the values of interleukin-1ß were normalized to control values when supplementing CGA (P < 0.05). DQ injection decreased serum superoxide dismutase activity, hepatic catalase activity, and serum and hepatic glutathione level, but increased malondialdehyde concentration in serum and liver (P < 0.05), and the values of these parameters (except hepatic catalase activity) were reversed by 500 and/or 1,000 mg/kg CGA. The results suggested that CGA could improve growth performance, alleviate oxidative stress, and ameliorate hepatic inflammation in DQ-challenged broilers.

Effects of L-theanine on intestinal morphology, barrier function, and MAPK signaling pathways in diquat-challenged piglets.

This study aimed to explore the protective effects of L-theanine supplementation on the diquat-challenged weaned piglets. A total of 160 weaned piglets were randomly divided into 4 groups using a 2 × 2 two-factor design, there were 4 replicates per group and 10 pigs per replicate. Piglets were fed diets (with 1000 mg/kg L-theanine addition or not), then challenged with diquat or saline on day 7. 21 days after challenge, two pigs from each replicate were selected for sample collection. Results showed that supplement with 1000 mg/kg L-theanine down-regulated the diarrhea rate, serum D-lactate level, tumor necrosis factor-α, and phosphorylation of extracellular regulated protein kinases (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) signaling in pigs without diquat challenge (p < 0.05). While for diquat-challenged piglets, L-theanine addition increased average daily gain, jejunum villus height, and interferon-γ level (p < 0.05). Meanwhile, L-theanine addition decreased the diarrhea rates and mortality, serum D-lactate level, and phosphorylation of ERK and JNK in diquat-challenged pigs (p < 0.05). These results demonstrate that L-theanine pretreatment could alleviate diquat-induced oxidative stress and improve intestinal barrier function in diquat-challenged weaned piglets, which can be attributed to suppression of MAPK phosphorylation signaling pathways.

[Effects and significance of continuous hemoperfusion on patients with diquat poisoning].

OBJECTIVE: To investigate the effect of continuous hemoperfusion (HP) on the levels of soluble CD14 isoform (sCD14-st) and neutrophil gelatinase-associated lipocalin (NGAL) on patients with diquat (DQ) poisoning and its significance. METHODS: A total of 86 patients with acute DQ poisoning admitted to the department of emergency medicine, Harrison International Peace Hospital Affiliated to Hebei Medical University from May 2018 to August 2021 were enrolled and divided into the intermittent HP group (40 cases) and the continuous HP group (46 cases) according to the random number table method. All patients received basic treatment and continuous veno-venous hemofiltration (CVVH) within 24 hours after admission. On this basis, the intermittent HP group received HP treatment within 2 hours, lasting 2 hours each time for every 8 hours, 3 times in all; the continuous HP group received continued HP treatment until there was no DQ component in urine samples. Serum NGAL levels were detected in all patients before treatment and at 3 hours, 12 hours, 24 hours, 2 days, 3 days, 5 days, and 7 days after treatment. At the same time, serum sCD14-st, blood lactate (Lac), arterial partial pressure of oxygen (PaO2), serum creatinine (SCr), MB isoenzyme of creatine kinase (CK-MB) and interleukin-18 (IL-18) levels were detected before treatment and at 24 hours, 3 days, and 7 days after treatment. Kaplan-Meier survival curve was drawn to analyze the 28-day survival of patients. RESULTS: Before treatment, there was no significant difference in serum NGAL, sCD14-st, Lac, PaO2, SCr, CK-MB and IL-18 levels between the two groups. With the prolongation of treatment, the serum levels of NGAL, sCD14-st, Lac, SCr, CK-MB and IL-18 in the intermittent HP group increased at first and then decreased. Serum levels of NGAL, sCD14-st, CK-MB and IL-18 reached their peaks at 24 hours after treatment, and the Lac and SCr levels reached their peaks at 3 days after treatment. In addition, the levels of the above indexes at each time point in the continuous HP group were all significantly lower than those in the intermittent HP group [after 24 hours of treatment: NGAL (µg/L) was 345.90±30.75 vs. 404.24±38.79, sCD14-st (ng/L) was 1 941.88±298.02 vs. 2 656.35±347.93, CK-MB (U/L) was 30.67±9.11 vs. 43.28±8.06, IL-18 (ng/L) was 139.49±16.29 vs. 177.98±27.85; 3 days of treatment: Lac (mmol/L) was 2.98±0.26 vs. 3.72±0.49, SCr (µmol/L) was 125.01±24.24 vs. 156.74±28.88; all P < 0.05]. However, there was no significant difference in PaO2 levels between the two groups at each time point after treatment. The Kaplan-Meier survival curve showed that the 28-day mortality of patients in the continuous HP group was significantly lower than that in the intermittent HP group [26.09% (12/46) vs. 52.50% (21/40); Log-Rank test: χ 2 = 7.288, P = 0.007]. CONCLUSIONS: Continuous HP could effectively reduce serum sCD14-st, NGAL levels and 28-day mortality in patients with DQ poisoning, with good curative effect.

[Determination of paraquat and diquat residues in urine samples based on solid-phase extraction and ultra performance liquid chromatography-high resolution mass spectrometry].

Determining the presence of paraquat (PQ) and diquat (DQ) in urine samples through physical and chemical testing is challenging. As PQ and DQ have characteristics such as high molecular polarity and good water solubility, they are difficult to be retained by conventional reversed-phase columns. Most of the methods in the literature use hydrophilic interaction chromatography (HILIC) for the retention of PQ and DQ, but they often require high concentrations of buffer salts as the mobile phase, which increase the contamination of the mass spectrometer. In view of the above problems, a rapid and accurate analysis method was developed for the determination of PQ and DQ residuals in urine samples based on weak cation exchange (WCX) solid-phase extraction (SPE) and ultra performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) in this study. Urine samples were first diluted with phosphate buffer (pH=6.86) and pretreated using the WCX SPE method. Chromatographic separation was performed on a Syncronis HILIC column (100 mm×2.1 mm, 1.7 µm). An electrospray ion source in the positive (ESI+) mode and full mass-data dependent MS2 (full mass-ddMS2) mode was used for quantification by matrix-matched external standard method. In this study, the concentration of ammonium formate in the mobile phase in the HILIC mode was effectively reduced to 10 mmol/L by the continuous optimization of the chromatographic conditions. MS optimization results indicated that the molecular ion (M+·) of PQ and DQ had the strongest response. In addition, sample pretreatment conditions were also optimized. The obtained results indicated that the hydrophobic polytetrafluoroethylene (PTFE) filter membrane, acetonitrile-water (1∶1, v/v) as a fixing solution, and polypropylene vials were suitable for PQ and DQ analysis. Under the optimal conditions, the linearity of PQ and DQ was good with correlation coefficients (r2) greater than 0.998. The limits of detection (LODs, S/N≥3) and limits of quantification (LOQs, S/N≥10) were 0.2 µg/L and 0.6 µg/L, respectively. Mean spiked recoveries of PQ and DQ at the four spiked levels (1.0, 20.0, 100.0, and 200.0 µg/L) were in the range of 85.8%-101% and 80.3%-86.9%, with the RSDs of 0.8%-5.1% and 0.9%-4.2%. The established method was employed for the analysis and confirmation of PQ and DQ for clinical poisoning cases. In one case, a 23-year-old male who had taken approximately 20 mL of pesticide orally was confirmed as DQ poisoning by the developed method. DQ concentration monitoring of the urine samples was conducted for this case during the clinical treatment process. The patient was successfully discharged from the hospital after five times of blood perfusion and other treatments until the DQ concentration was low in the urine samples. In conclusion, the method developed in this study based on WCX SPE-UPLC-HRMS can be used for the confirmation of poisoning cases and concentration monitoring during clinical treatment, providing strong technical support for clinical precision treatment. The method is rapid, simple, sensitive, and accurate, and it is suitable for the detection of PQ and DQ in urine samples.

Identification of differentially expressed genes and pathways in diquat and paraquat poisoning using bioinformatics analysis.

OBJECTIVE: In this study, differentially expressed genes (DEGs) and signaling pathways involved in diquat (DQ) and paraquat (PQ) poisoning were identified via bioinformatics analysis, in order to inform the development of novel clinical treatments. METHODS: Raw data from GSE153959 were downloaded from the Gene Expression Omnibus database. DEGs of the DQ vs. control (CON) and PQ vs. CON comparison groups were identified using R, and DEGs shared by the two groups were identified using TBtools. Subsequently, the shared DEGs were searched in the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, using the Database for Annotation, Visualization, and Integrated Discovery. A protein-protein interaction (PPI) network was constructed, and hub genes were identified using the cytoHubba plug-in in Cytoscape software. Finally, circos and contrast plots showing the DEGs shared between mouse and human chromosomes were constructed using TBtools. RESULTS: Thirty-one DEGs shared by the DQ and PQ groups were identified. Enriched biological process terms included positive regulation of cell proliferation and translation. Enriched cellular component terms included extracellular region, intracellular membrane-bounded organelle and mitochondrion. Enriched molecular function terms included transcription factor activity and sequence-specific double-stranded DNA binding. Enriched KEGG pathways included the interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, and human T-cell leukemia virus 1 infection. The top 10 hub genes in the PPI network were prostaglandin-endoperoxide synthase 2 (Ptgs2), chemokine (C-X-C motif) ligand 2 (Cxcl2), colony-stimulating factor 2 (granulocyte-macrophage) (Csf2), matrix metallopeptidase 13 (Mmp13), amphiregulin (Areg), plasminogen activator, urokinase receptor (Plaur), fos-like antigen 1 (Fosl1), epiregulin (Ereg), activating transcription factor 3 (Atf3), and transferrin receptor (Tfrc). Cxcl2, Csf2, and Atf3 played important roles in the mitogen-activated protein kinase (MAPK) signaling pathway. CONCLUSIONS: These pathways and DEGs may serve as targets for gene therapy.

Deposition of diquat with different spray tips, efficiency on common water hyacinth, and effect on water quality

Eichhornia crassipes, known as common water hyacinth, has a high growth rate and produces large amounts of biomass when there are imbalances in water bodies, making it one of the worst aquatic weeds in the world. A study was carried out under small water reservoir field conditions to evaluate the herbicide diquat (960 g ha−1) in controlling this species, at the adult stage development. Four spray tips (AI 11002VS, XR 11002VS and, TXVK-8 with spray volume of 200 L ha−1 and XR 11003VS with 400 L ha−1) were tested. Spraying was performed using a CO2-pressurized sprayer under constant pressure attached to a boat. Plant control was visually evaluated at 1, 3, 7, 11, 14, 21, 29, 60, 87, and 98 days after herbicide application and dry matter accumulation was determined at the end of the experimental period, as well as the spray solution deposition in the application area and water physical and chemical quality. The herbicide diquat was efficient in controlling E. crassipes plants at the dose applied and in development stage of the studied plants, regardless of the type of spray tip at the end of the evaluations. At the beginning of evaluations, the spray tip XR 11002VS was the least effectivity in controlling water hyacinth plants. Spray solution losses were high in all tips tested for control of E. crassipes plants, and the spray tips AI 11002VS and XR 11003VS provided the lowest losses during spraying. No water physical or chemical characteristics were negatively affected by diquat application.