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.

COMPARATIVE HYGIENIC ASSESSMENT OF THE POTENTIAL DIQUAT HAZARD TO THE POPULATION WHEN CONSUMING AGRICULTURAL CROPS TREATED WITH THE REGLONE AIR 200 SL FORMULATION USING DIFFERENT APPLICATION TECHNOLOGIES (UAV, AERIAL, HIGH-CLEARANCE ROD SPRAYER TREATMENT).

OBJECTIVE: The aim: Assessment of the hazard to the population when consuming treated crops by using different technologies. PATIENTS AND METHODS: Materials and methods: Unmanned aerial vehicle XAG XPlanet 2020 equipped with four rotating rotors, which allows to keep in the air a 20-liter tank was used for spraying field; a manned aircraft AN-2 aggregated with a serial sprayer. High-clearance rod treatment of sunflower and rapeseed crops was carried out by using a PLA MAP II 2010 tractor. RESULTS: Results: When the herbicide was applied by aerial application with UAV, the initial content of diquat dibromide in treated rapeseed and sunflower plants on the day of treatment was significantly higher than in the soil under crops (р≤0.05). The analysis of the diquat content dynamics in sunflower also showed a similar behavior of the a.i. in the plant after processing by another application methods: UAV, aerial and high-clearance rod treatment. The integral index of hazard when using pesticide-contaminated products (IIHPCPC) = ADD+С+ DT50 = 4+1+1 = 6 points. That is why, diquat dibromide can be classified according to this index can be classified as compound of 3rd hazard class. CONCLUSION: Conclusions: As a result of the conducted researches, it was established that the content of diquat in rapeseed and sunflower samples grown with the Reglone Air 200 SL application (after treatment and before harvesting) was below the maximum residue levels in those crops. There are no statistically significant differences in the behavior of diquat dibromide when applying by different methods of application (UAV, aerial, high-clearance rod treatment) in different agro-climatic zones of Ukraine.

In vivo toxicological assessment of diquat dibromide: cytotoxic, genotoxic, and biochemical approach.

Diquat dibromide is a comprehensive herbicide commonly used in the cultivation of cotton, soybeans, and other crops to combat unwanted weeds. In this study, the half-maximal effective concentration (EC50) value of diquat dibromide was determined 60 mg/L in the Allium root growth inhibition test. ½ × EC50 (30 mg/L), EC50 (60 mg/L), and 2 × EC50 (120 mg/L) concentrations of diquat dibromide were applied to Allium cepa L. bulbs for 72 h to investigate the dose-dependent toxic effects. To determine the toxic effects cytogenetic, biochemical and physiological parameters were used. Physiological effects were investigated by determination of the percentage of rooting, relative injury rate, root length, and weight gain. Genetic effects were evaluated by the frequency of chromosomal abnormalities (CAs), micronucleus (MN) formation, mitotic index (MI) rate, and comet assay. Biochemical parameters were evaluated with antioxidant enzyme activities and lipid peroxidation by determining malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, catalase (CAT) activity, and glutathione (GSH) level. Also, chlorophyll pigment contents (a, b, and total) in green leaves were calculated to elucidate the effect of diquat dibromide on plants and the biosphere. The findings show that increasing doses of diquat dibromide caused a decrease in all physiological parameters and MI ratio, promoting MN and CAs and tail DNA formation in genetic parameters. It was determined by the increases in MDA level, SOD, and CAT activities and decreases in GSH levels that diquat dibromide administration caused oxidative stress depending on the dose. Also, chlorophyll pigment levels (a, b, and total) measured in leaf tissues decreased with the application dose. Considering that the toxic effects caused by diquat dibromide and that organisms other than unwanted plants will be exposed during the application, its use should be abandoned and biocontrol methods should be used instead. In cases where use is compulsory, doses that will not harm the environment and organisms should be determined and used.

Optimized liquid chromatography tandem mass spectrometry approach for the determination of diquat and paraquat herbicides.

Liquid chromatography tandem mass spectrometry (LC-MS/MS) determination of quaternary ammonium herbicides diquat (DQ) and paraquat (PQ) can be very challenging due to their complicated chromatographic and mass spectrometric behaviors. Various multiple reaction monitoring (MRM) transitions from radical cations M(+) and singly charged cations [M-H](+), have been reported for LC-MS/MS quantitation under different chromatographic and mass spectrometric conditions. However, interference peaks were observed for certain previously reported MRM transitions in our study. Using a Dionex Acclaim(®) reversed-phase and HILIC mixed-mode LC column, we evaluated the most sensitive MRM transitions from three types of quasi-molecular ions of DQ and PQ, elucidated the cross-interference phenomena, and demonstrated that the rarely mentioned MRM transitions from dications M(2+) offered the best selectivity for LC-MS/MS analysis. Experimental parameters, such as IonSpray (IS) voltage, source temperature, declustering potential (DP), column oven temperature, collision energy (CE), acid and salt concentrations in the mobile phases were also optimized and an uncommon electrospray ionization (ESI) capillary voltage of 1000V achieved the highest sensitivity. Employing the proposed dication transitions 92/84.5 for DQ and 93/171 for PQ, the direct aqueous injection LC-MS/MS method developed was able to provide a method detection limit (MDL) of 0.1µg/L for the determination of these two herbicides in drinking water.

Determination of paraquat and diquat in human body fluids by high-performance liquid chromatography/tandem mass spectrometry.

Paraquat (PQ) and diquat (DQ) in human whole blood and urine were analyzed by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) with positive ion electrospray ionization (ESI). The compounds were extracted with Sep-Pak C18 cartridges from whole blood and urine samples containing ethyl paraquat as an internal standard. The separation of PQ and DQ was carried out using ion-pair chromatography with heptafluorobutyric acid in 20 mM ammonium acetate and acetonitrile gradient elution for successful coupling with MS. Both compounds formed base peaks due to [M-H]+ ions by HPLC/ESI-MS and the product ions produced from each [M-H]+ ion by HPLC/MS/MS. Selective reaction monitoring (SRM) showed much higher sensitivity for both body fluids. Therefore, a detailed procedure for the detection of compounds by SRM with HPLC/MS/MS was established and carefully validated. The recoveries of PQ and DQ were 80.8-95.4% for whole blood and 84.2-96.7% for urine. The calibration curves for PQ and DQ showed excellent linearity in the range of 25-400 ng ml(-1) of whole blood and urine. The detection limits were 10 ng ml(-1) for PQ and 5 ng ml(-1) for DQ in both body fluids. The intra- and inter-day precision for both compounds in whole blood and urine samples were not greater than 13.0%. The data obtained from the determination of PQ and DQ in rat blood after oral administration of the compounds are also presented.

Pathogenesis of diquat-induced liver necrosis in selenium-deficient rats: assessment of the roles of lipid peroxidation and selenoprotein P.

A dose of diquat below the amount injurious to selenium-replete animals causes lipid peroxidation and massive liver necrosis in selenium-deficient rats. The current study was undertaken to characterize the lipid peroxidation with respect to the liver injury and to correlate the presence of several selenoproteins with the protective effect of selenium. Lipid peroxidation was assessed by measurement of F2 isoprostanes. Diquat caused an increase in liver and plasma F2 isoprotanes. A gradient of these compounds was detected across the liver in some animals, indicating that this organ was a source of some of the plasma F2 isoprostanes. A time-course experiment showed that liver F2 isoprostane concentration increased before plasma alanine transaminase (ALT) levels rose. Selenium-deficient rats were injected with selenium doses from 2 to 50 micrograms/kg and studied 12 hours later. A dose of 10 micrograms/kg or more prevented diquat-induced lipid peroxidation and liver injury. This dose increased plasma selenoprotein P substantially, and a dose-response was present. Liver cellular and plasma glutathione peroxidase activities remained below 2% of their values in control rats for all selenium doses. In selenium-deficient rats given diquat, hepatic lipid peroxidation precedes hepatic necrosis and could therefore be an important mechanism of the necrosis. Selenoprotein P levels were increased by selenium injections, which protected against diquat injury, but glutathione peroxidase activity was not increased. This is consistent with selenoprotein P being the mediator of the selenium effect.

An assessment of the role of redox cycling in mediating the toxicity of paraquat and nitrofurantoin.

The abilities of paraquat, diquat, and nitrofurantoin to undergo cyclic oxidation and reduction with rat microsomal systems have been assessed and compared to that of the potent redox cycler, menadione. Diquat and menadione were found to be potent redox cyclers with comparable abilities to elicit a nonstoichiometric increase in both the consumption of O2 and the oxidation of NADPH, compared to the amounts of substrate added. In contrast, paraquat and nitrofurantoin redox cycled poorly, being an order of magnitude less potent than either diquat or menadione. This was reflected in kinetic studies using lung and liver microsomes, which showed that NADPH-cytochrome P-450 reductase had a lower affinity (Km) for paraquat and nitrofurantoin than for menadione and diquat, although values of Vmax were comparable for all the substrates except nitrofurantoin, which was lower. In order to assess redox cycling of the substrates in an intact lung system, the O2 consumption of rat lung slices was measured in the presence of all four compounds. A small increase in lung slice O2 uptake was observed with paraquat (10(-5) M) in the first 2.5 hr of incubation, possibly because of redox cycling of a high intracellular concentration of paraquat resulting from active accumulation into target cells. This stimulation in O2 uptake was no longer observed when slices were incubated for a longer period or with higher paraquat concentrations (10(-4) M), possibly because of toxic effects in target cells. High concentrations of diquat (10(-5) M) had no effect on O2 consumption of lung slices.(ABSTRACT TRUNCATED AT 250 WORDS)