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1.
Article de Anglais | MEDLINE | ID: mdl-39096375

RÉSUMÉ

Dichlorvos is an organophosphate pesticide that is commonly used for agricultural and domestic control of pests and insects. Despite its usefulness, it exerts reproductive toxicity and induces male sexual dysfunction. On the other hand, curcumin has been reported to improve sexual dysfunction. However, till date, no study has reported the impact of curcumin on dichlorvos-induced sexual dysfunction. This study investigated the effect and associated mechanism of curcumin on dichlorvos-induced sexual dysfunction. Thirty-two male Wistar rats were randomized into four groups; the control (1 mL of olive oil), curcumin-treated (100 mg/kg), DDVP-treated (98.54 g/m3 of dichlorvos by inhalation), and DDVP + Curcumin-treated. Dichlorvos induced sexual dysfunction as depicted by reduced motivation to mate (8.38 ± 0.18 vs. 4.00 ± 0.33, P < 0.0001), prolonged latencies (46.63 ± 1.30 vs. 98.75 ± 1.32, P < 0.0001) and reduced frequencies of mount (14.88 ± 0.52 vs. 8.63 ± 0.38), intromission (9.38 ± 0.50 vs. 3.75 ± 0.31, P < 0.0001), and ejaculation (7.63 ± 0.38 vs. 1.50 ± 0.19, P < 0.0001). These findings were accompanied by suppression of hypothalamic-pituitary-testicular axis, evidenced by marked reductions in circulating FSH (60.00 ± 1.04 vs. 21.13 ± 0.52, P < 0.0001), LH (46.38 ± 1.38 vs. 19.00 ± 0.46, P < 0.0001), and testosterone (6.01 ± 0.50 vs. 0.74 ± 0.05, P < 0.0001). Nonetheless, the administration of curcumin in dichlorvos-exposed rats significantly attenuated dichlorvos-induced sexual dysfunction by improving the assessed indices of male sexual act. Also, curcumin significantly increased serum levels of FSH (21.13 ± 0.52 vs. 47.25 ± 0.10, P < 0.0001), LH (19.00 ± 0.46 vs. 43.00 ± 1.49), and testosterone (0.74 ± 0.05 vs. 3.98 ± 0.08, P < 0.0001). This study revealed that curcumin attenuated dichlorvos-induced sexual dysfunction by activating the hypothalamic-pituitary-testicular axis and upregulating circulating testosterone.

2.
Biomed Pharmacother ; 178: 117136, 2024 Jul 26.
Article de Anglais | MEDLINE | ID: mdl-39067166

RÉSUMÉ

BACKGROUND: The continuous use of pesticides, such as dichlorvos, is a common agricultural and domestic practice. However, it is associated with shortfalls like testicular toxicity through the induction of oxidative stress-mediated signaling. On the other hand, L-arginine, a precursor of nitric oxide, has been reported to exert antioxidant activities and thus may attenuate dichlorvos-induced testicular toxicity. AIM: Hence, this study was designed to evaluate the effect of L-arginine treatment on dichlorvos-induced testicular toxicity. MATERIALS AND METHODS: Forty male Wistar rats were randomly assigned into four equal groups. The control rats were administered 0.5 mL of distilled water, dichlorvos- (DDVP-) treated rats were exposed to DDVP via inhalation for 15 min, DDVP + L-arginine-treated rats were exposed to DDVP and also received 100 mg/kg b.w/day, while L-arginine-treated rats received 100 mg/kg b.w/day. RESULTS: DDVP exposure significantly reduced testicular nitric oxide, relative testicular weight, lowered sperm count, viability, and motility, and suppressed serum FSH, LH, and testosterone levels. These findings were associated with a rise in testicular malondialdehyde, TNF-α, IL-6, and 8OHdG levels and caspase 3 activities, and a reduction in GSH and superoxide dismutase. Additionally, on histopathological examination, DDVP was observed to reduce mature sperm cells in the seminiferous tubular lumen and induce focal vascular congestion in the interstitial space. Nonetheless, L-arginine treatment significantly attenuated DDVP-induced biochemical and histological alterations. CONCLUSION: This study showed that L-arginine attenuated testicular toxicity by improving epididymal sperm variables and male sex hormones by suppressing oxidative stress, inflammation, and apoptosis in DDVP-exposed rats.

3.
Mar Pollut Bull ; 206: 116669, 2024 Jul 09.
Article de Anglais | MEDLINE | ID: mdl-38991609

RÉSUMÉ

Dichlorvos (DDVP) is a widely used organophosphorus pesticide (OPP) that has been frequently detected in the marine environment of China. Water quality criteria (WQC) is however not available for this emergent pollutant in the marine environment, which hinders its ecological risk assessment. This study, therefore, screened toxicity values of DDVP and conducted toxicity tests on six marine species to supplement toxicity data. The WQC for DDVP was derived with the species sensitivity distribution (SSD) methodology, based on which the ecological risk of DDVP in the seawater of China was assessed. The results showed that the recommended short-term (SWQC) and long-term water quality criteria (LWQC) for DDVP were 1.47 and 0.0521 µg/L, respectively. Most marine waters of China showed low or negligible risk (HQ < 1, ORP < 2 %), whereas some estuarine waters warrant further concern due to higher risk. This study provides the scientific basis for seawater quality standard formulation and ecological risk management for DDVP.

4.
Cureus ; 16(5): e60417, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38882963

RÉSUMÉ

Background and objective Several blood biochemical parameters are used to biomonitor coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Reduced serum cholinesterase (ChE) has been suggested to be a predictive indicator of the severity and outcome of COVID-19 infection. This study aimed to examine serum ChE activity in hospitalized and terminally ill COVID-19 patients with cytokine storm and evaluate the enzyme for the in vitro ChE-inhibitory activity of the organophosphate dichlorvos. Methods We determined the serum ChE activity, electrometrically, among hospitalized COVID-19-cytokine storm patients and their non-cytokine storm counterparts. Aliquots of serum samples from healthy volunteers, COVID-19-cytokine storm patients, and non-cytokine storm COVID-19 patients were pooled separately. They were incubated in vitro for 10 minutes with dichlorvos at 0.25 or 0.5 µM. Serum samples from the three groups were subjected to ChE inhibition temporally (5-60 minutes) by 0.25 µM dichlorvos to evaluate the kinetics of enzyme inhibition using steady-state kinetics. Results Of the 165 hospitalized patients with COVID-19, 33 (20%) suffered from the cytokine storm. Serum ChE activity of female COVID-19 patients with cytokine storm was significantly lower than that of the non-cytokine storm counterparts. Risk analysis of reduced serum ChE activity (≥20%) among the 33 COVID-19 patients with cytokine storm compared to 111 non-cytokine storm COVID-19 patients revealed that the former were significantly at risk of reduced enzyme activity. In vitro, dichlorvos at 0.25 µM and 0.5 µM significantly inhibited serum ChE activity in all the groups. The COVID-19-cytokine storm group was the least affected. Dichlorvos at 0.25 µM progressively (5-60 minutes) inhibited serum ChE activity. The inhibition kinetic parameters in COVID-19-cytokine storm patients showed a decrease in the half-life of inhibition (14.54%), inhibition rate (51.46%), and total inhibition time (14.55%). Conclusions Reduced serum ChE in COVID-19 patients with cytokine storm could be adopted as a potential additional laboratory examination tool for bedside risk assessment. The in vitro inhibition profile of serum ChE activity by dichlorvos in COVID-19-cytokine storm patients suggests reduced susceptibility of the enzyme to inhibition. The response of COVID-19 patients to ChE-inhibiting medications should be cautiously evaluated with prior in vitro tests.

5.
J Agric Food Chem ; 72(19): 11205-11220, 2024 May 15.
Article de Anglais | MEDLINE | ID: mdl-38708789

RÉSUMÉ

Chlorpyrifos (CPF), dichlorvos (DDV), and cypermethrin (CP), as commonly used pesticides, have been implicated in inducing neuropsychiatric disorders, such as anxiety, depression-like behaviors, and locomotor activity impairment. However, the exact molecular mechanisms of these adverse effects, particularly in both sexes and their next-generation effects, remain unclear. In this study, we conducted behavioral analysis, along with cellular assays (monodansylcadaverine staining) and molecular investigations (qRT-PCR and western blotting of mTOR, P62, and Beclin-1) to clear the potential role of autophagy in pesticide-induced behavioral alterations. For this purpose, 42 adult female and 21 male inbred ICR mice (F0) were distributed into seven groups. Maternal mice (F0) and 112 F1 offspring were exposed to 0.5 and 1 ppm of CPF, DDV, and CP through drinking water. F1 male and female animals were studied to assess the sex-specific effects of pesticides on brain tissue. Our findings revealed pronounced anxiogenic effects and impaired locomotor activity in mice. F1 males exposed to CPF (1 ppm) exhibited significantly elevated depression-like behaviors compared to other groups. Moreover, pesticide exposure reduced mTOR and P62 levels, while enhancing the Beclin-1 gene and protein expression. These changes in autophagy signaling pathways, coupled with oxidative and neurogenic damage in the cerebral cortex and hippocampus, potentially contribute to heightened locomotor activity, anxiety, and depression-like behaviors following pesticide exposure. This study underscores the substantial impact of pesticides on both physiological and behavioral aspects, emphasizing the necessity for comprehensive assessments and regulatory considerations for pesticide use. Additionally, the identification of sex-specific responses presents a crucial dimension for pharmaceutical sciences, highlighting the need for tailored therapeutic interventions and further research in this field.


Sujet(s)
Anxiété , Autophagie , Comportement animal , Dépression , Souris de lignée ICR , Stress oxydatif , Pesticides , Animaux , Femelle , Mâle , Souris , Autophagie/effets des médicaments et des substances chimiques , Anxiété/induit chimiquement , Anxiété/physiopathologie , Anxiété/métabolisme , Dépression/métabolisme , Dépression/génétique , Dépression/induit chimiquement , Dépression/physiopathologie , Stress oxydatif/effets des médicaments et des substances chimiques , Pesticides/toxicité , Pesticides/effets indésirables , Comportement animal/effets des médicaments et des substances chimiques , Locomotion/effets des médicaments et des substances chimiques , Humains , Sérine-thréonine kinases TOR/métabolisme , Sérine-thréonine kinases TOR/génétique , Chlorpyriphos/toxicité , Chlorpyriphos/effets indésirables
6.
Heliyon ; 10(10): e31217, 2024 May 30.
Article de Anglais | MEDLINE | ID: mdl-38813177

RÉSUMÉ

We developed a novel chromogenic reagent and sensor by selective approach, for the detection and identification of dichlorvos, which we tested with the thin layer chromatography method. For the first time, we reported in situ-generated glyoxal as a hydrolysis product, which then interacts with isoniazid to produce a yellow-colored cyclic compound. We used well-known spectroscopic techniques to confirm the chemical identity of the final product. We initially investigated the reaction using a variety of approaches, followed by attempts to establish the reaction mechanism using Density Functional Theory by Gaussian software.

7.
Food Chem ; 452: 139580, 2024 Sep 15.
Article de Anglais | MEDLINE | ID: mdl-38744129

RÉSUMÉ

The absence of high-affinity antibodies has hindered the development of satisfactory immunoassays for dichlorvos (DDVP) and trichlorfon (TCP), two highly toxic organophosphorus pesticides. Herein, the de novo synthesis of a novel anti-DDVP hapten was introduced. Subsequently, a specific anti-DDVP monoclonal antibody (Mab) was produced with satisfying affinity to DDVP (IC50: 12.4 ng mL-1). This Mab was highly specific to DDVP, and TCP could readily convert into DDVP under mild alkaline conditions. Leveraging this insight, an indirect competitive ELISA was successfully developed for simultaneous detection of DDVP and TCP. The limit of detection in rice, cabbage and apple for DDVP /TCP was found to be 12.1/14.6 µg kg-1, 7.3/8.8 µg kg-1 and 6.9/8.3 µg kg-1, respectively. This study not only provides an effective strategy for producing a high-quality anti-DDVP Mab but also affords a reliable and cost-effective tool suitable for high-throughput detection of DDVP and TCP in food samples.


Sujet(s)
Anticorps monoclonaux , Dichlorvos , Test ELISA , Contamination des aliments , Haptènes , Oryza , Trichlorfon , Haptènes/composition chimique , Haptènes/immunologie , Anticorps monoclonaux/immunologie , Anticorps monoclonaux/composition chimique , Animaux , Contamination des aliments/analyse , Test ELISA/méthodes , Dichlorvos/analyse , Oryza/composition chimique , Oryza/immunologie , Trichlorfon/analyse , Trichlorfon/immunologie , Souris , Souris de lignée BALB C , Malus/composition chimique , Brassica/composition chimique , Brassica/immunologie , Dosage immunologique/méthodes
8.
Arh Hig Rada Toksikol ; 75(1): 81-84, 2024 Mar 01.
Article de Anglais | MEDLINE | ID: mdl-38548379

RÉSUMÉ

Organophosphorus poisoning is a critical condition that can cause central nervous system depression, respiratory failure, and death early on. As its clinical manifestations closely resemble those of carbamate pesticide poisoning, the aim of this case study is to present a case of misdiagnosis, initially identifying carbofuran poisoning as organophosphate in a patient suspect of a heatstroke. We also present a case of intentional self-poisoning with organophosphate dichlorvos to underline the likelihood of pesticide poisoning in patients exhibiting acute cholinergic symptoms when the ingested substance is not known. In such cases, empirical treatment with atropine and oxime can be started pending timely differential diagnosis to adjust treatment as necessary.


Sujet(s)
Insecticides , Intoxication aux organophosphates , Pesticides , Intoxication , Humains , Carbamates/usage thérapeutique , Intoxication aux organophosphates/diagnostic , Intoxication aux organophosphates/traitement médicamenteux , Dichlorvos/usage thérapeutique , Intoxication/thérapie
9.
Anal Chim Acta ; 1292: 342243, 2024 Mar 01.
Article de Anglais | MEDLINE | ID: mdl-38309847

RÉSUMÉ

BACKGROUND: Dichlorvos (DDVP), as a highly effective insecticide, is widely used in agricultural production. However, DDVP residue in foodstuffs adversely affects human health. Conventional instrumental analysis can provide highly sensitive and accurate detection of DDVP, while the need of bulky and expensive equipment limits their application in resource-poor areas and on-site detection. Therefore, the development of easily portable sensing platforms for convenient, rapid and sensitive quantification of DDVP is very essential for ensuring food safety. RESULT: A portable colorimetric sensing platform for rapid and sensitive quantification of DDVP is developed based on nanozyme-participated highly efficient chromogenic catalysis. The Fe-Mn bimetallic oxide (FeMnOx) nanozyme possesses excellently oxidase-like activity and can efficiently catalyze oxidation of 3, 3', 5, 5'-tetramethylbenzidine (TMB) into a blue oxide with a very low Michaelis constant (Km) of 0.0522 mM. The nanozyme-catalyzed chromogenic reaction can be mediated by DDVP via inhibiting the acetylcholinesterase (AChE) activity. Thus, trace DDVP concentration-dependent color evolution is achieved and DDVP can be sensitively detected by spectrophotometry. Furthermore, a smartphone-integrated 3D-printed miniature lightbox is fabricated as the colorimetric signal acquisition and processing device. Based on the FeMnOx nanozyme and smartphone-integrated lightbox system, the portable colorimetric sensing platform of DDVP is obtained and it has a wide linear range from 1 to 3000 ng mL-1 with a low limit of detection (LOD) of 0.267 ng mL-1 for DDVP quantification. SIGNIFICANCE: This represents a new portable colorimetric sensing platform that can perform detection of DDVP in foodstuffs with simplicity, sensitivity, and low cost. The work not only offers an alternative to rapid and sensitive detection of DDVP, but also provides a new insight for the development of advanced sensors by the combination of nanozyme, 3D-printing and information technologies.


Sujet(s)
Dichlorvos , Pesticides , Humains , Colorimétrie , Oxydes , Acetylcholinesterase , Catalyse , Peroxyde d'hydrogène
10.
Environ Res ; 242: 117600, 2024 Feb 01.
Article de Anglais | MEDLINE | ID: mdl-37939806

RÉSUMÉ

Dichlorvos (2,2-Dichlorovinyl dimethyl phosphate, [DDVP]) belongs to the class of organophosphates and is widely used as an insecticide in agriculture farming and post-harvest storage units. Extensive research has been conducted to assess the factors responsible for the presence of DDVP in terrestrial and aquatic ecosystems, as well as the entire food chain. Numerous studies have demonstrated the presence of DDVP metabolites in the food chain and their toxicity to mammals. These studies emphasize that both immediate and chronic exposure to DDVP can disrupt the host's homeostasis, leading to multi-organ damage. Furthermore, as a potent carcinogen, DDVP can harm aquatic systems. Therefore, understanding the contamination of DDVP and its toxicological effects on both plants and mammals is vital for minimizing potential risks and enhancing safety in the future. This review aimed to comprehensively consolidate information about the distribution, ecological effects, and health impacts of DDVP, as well as its metabolism, detection, prevention, and remediation strategies. In summary, this study observes the distribution of DDVP contaminations in vegetables and fruits, resulting in significant toxicity to humans. Although several detection and bioremediation strategies are emerging, the improper application of DDVP and the alarming level of DDVP contamination in foods lead to human toxicity that requires attention.


Sujet(s)
Dichlorvos , Insecticides , Composés organiques du phosphore , Animaux , Humains , Dichlorvos/toxicité , Dichlorvos/métabolisme , Écosystème , Insecticides/toxicité , Mammifères/métabolisme
11.
Talanta ; 269: 125404, 2024 Mar 01.
Article de Anglais | MEDLINE | ID: mdl-37980819

RÉSUMÉ

Monitoring the residual dichlorvos (O,O-dimethyl-O-2,2-dichlorovinylphosphate, DDVP) in food has received extensive attention owing to its large consumption in agriculture. However, the previous sensing methods are not time-efficient enough due to the long incubation time for enzyme inhibition (tens of minutes to hours) or bottlenecked by the complicated procedures for senor fabrication. Herein, a novel sensing strategy is proposed based on the hydrolysis of DDVP into PO43-. By using alkaline phosphatase for hydrolysis, a certain portion of DDVP was transformed to PO43- within only 8 min. Then, the released PO43- was detected by a fluorescent terbium metal-organic framework (Tb-MOF). The coordination of the naked P-O groups to the metal nodes of the Tb-MOF disturbed the antenna effects of its ligands. Thus, DDVP was quantified by the decrease of the fluorescence of Tb ions. Based on this method, DDVP residues on plum surfaces were collected by swabs and successfully detected. The recovery of DDVP was determined in the range from 105 % to 115 %, demonstrating the quantification accuracy of this method. The detection limit reached 4.7 µM, which was lower than the restricted amount in fruit set by the National Standard of China. The present method provides an efficient and user-friendly way for the detection of DDVP and many other organophosphorus pesticides in food.

12.
Article de Chinois | WPRIM (Pacifique Occidental) | ID: wpr-1018964

RÉSUMÉ

Objective:The aim of this study was to investigate the clinical characteristics and analyze the risk factors of patients with acute dichlorvos poisoning combined with shock.Methods:The clinical data of patients with acute dichlorvos poisoning admitted to the Peking University Third Hospital and the Fifth Medical Center of the PLA General Hospital between January 2019 and September 2020 were retrospectively analyzed, and demographic data, poisoning, clinical manifestations, laboratory tests, therapeutic measures and clinical outcomes were collected to establish a clinical database. The patients were divided into two groups: the shock group and the non-shock group, and the clinical data were compared between the two groups to analyze the clinical characteristics and prognosis of shock in acute dichlorvos poisoning, and the risk factors of shock in acute dichlorvos poisoning were analyzed by logistic regression.Results:A total of 134 patients who met the criteria for acute dichlorvos poisoning were included in this study; the incidence of shock within 24 hours of admission was 39.6% (53/134), and 11 patients (8.21%) died in hospital; the in-hospital morbidity and mortality rate of patients in the shock group was higher than that in the non-shock group (20.8% vs. 0.0%, P<0.001). Symptoms of sphincter relaxation, coma, hypothermia, and organ function damage were more common in the shock group than in the non-shock group; and shock patients had longer hospitalization, ICU stay, and invasive ventilator use. Binary logistic regression analysis showed that the presence of sphincter relaxation manifestations ( OR=10.888, 95% CI: 1.677-70.684, P=0.012) was an independent risk factor for comorbid shock in patients with acute dichlorvos poisoning, and the use of cholinesterase reanimators ( OR=0.246, 95% CI: 0.072-0.846, P=0.026) was a protective factor for combined shock in patients with acute dichlorvos poisoning. Conclusions:The incidence of shock in patients with acute dichlorvos poisoning is high and affects the clinical prognosis, and the presence of sphincter relaxation and the absence of cholinesterase reenergizers are independent risk factors for combined shock in patients with acute dichlorvos poisoning.

13.
Iran J Public Health ; 52(11): 2440-2449, 2023 Nov.
Article de Anglais | MEDLINE | ID: mdl-38106827

RÉSUMÉ

Background: A green sample preparation method named deep eutectic solvent-based single drop microextraction (DES-SDME) was developed and optimized for determining trace metribuzin, dichlorvos, and fenthion. Methods: Two hundred seventy experimental runs were performed, and the optimal values of the five influential factors in the DES-SDME method were determined. The design of the study was based on one factor at a time and the peak area of high-performance liquid chromatography was used as a benchmark for comparing analysis results. Results: After optimizing the effective factors, the linearity range, detection limit and quantification limit of the method were determined by drawing calibration curves for the studied analytes. Conclusion: The results indicated the success of the developed method in obtaining acceptable figures of merit as a green preparation method with accuracy and precision.

14.
Environ Sci Pollut Res Int ; 30(60): 125664-125676, 2023 Dec.
Article de Anglais | MEDLINE | ID: mdl-38001290

RÉSUMÉ

Trichlorfon, one of the most widely used organophosphate insecticides, is commonly employed in aquaculture and agriculture to combat parasitic infestations. However, its inherent instability leads to rapid decomposition into dichlorvos (DDVP), increasing its toxicity by eightfold. Therefore, the environmental effects of trichlorfon in real-world scenarios involve the combined effects of trichlorfon and its degradation product, DDVP. In this study, we systematically investigated the degradation of trichlorfon in tap water over time using HPLC and LC-MS/MS analysis. Subsequently, an experiment was conducted to assess the acute toxicity of trichlorfon and DDVP on goldfish (Carassius auratus), employing a 1H NMR-based metabolic approach in conjunction with serum biochemistry, histopathological inspection, and correlation network analysis. Exposure to trichlorfon and its degradation product DDVP leads to increased lipid peroxidation, reduced antioxidant activity, and severe hepatotoxicity and nephrotoxicity in goldfish. Based on the observed pathological changes and metabolite alterations, short-term exposure to trichlorfon significantly affected the liver and kidney functions of goldfish, while exerting minimal influence on the brain, potentially due to the presence of the blood-brain barrier. The changes in the metabolic profile indicated that trichlorfon and DDVP influenced several pathways, including oxidative stress, protein synthesis, energy metabolism, and nucleic acid metabolism. This study demonstrated the applicability and potential of 1H NMR-based metabonomics in pesticide environmental risk assessment, providing a feasible method for the comprehensive study of pesticide toxicity in water environments.


Sujet(s)
Insecticides , Pesticides , Animaux , Trichlorfon/analyse , Dichlorvos/toxicité , Dichlorvos/analyse , Poisson rouge/métabolisme , Chromatographie en phase liquide , Spectroscopie par résonance magnétique du proton , Spectrométrie de masse en tandem , Insecticides/analyse , Pesticides/analyse , Eau/métabolisme
15.
Article de Chinois | MEDLINE | ID: mdl-37805431

RÉSUMÉ

Dichlorvos poisoning can cause muscarinic (M) -like symptoms, nicotinoid (N) -like symptoms and central nervous system manifestations. When severe poisoning is combined with refractory shock, the mortality rate exceeds 60%. At present, there are more and more studies on ECMO for poisoning, but there is no report on ECMO for treating refractory hypotension caused by dichlorvos poisoning. We analyzed 3 successful cases of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in the treatment of refractory shock caused by acute severe dichlorvos poisoning to explore the effectiveness of VA-ECMO in patients with severe poisoning.


Sujet(s)
Dichlorvos , Oxygénation extracorporelle sur oxygénateur à membrane , Humains , Oxygénation extracorporelle sur oxygénateur à membrane/méthodes , Choc cardiogénique/thérapie , Études rétrospectives
16.
J Pharm Sci ; 112(12): 3224-3232, 2023 12.
Article de Anglais | MEDLINE | ID: mdl-37722451

RÉSUMÉ

Remdesivir (RDV) and tenofovir alafenamide (TAF) are prodrugs designed to be converted to their respective active metabolites. Plasma protein binding (PPB) determination of these prodrugs is important for patients with possible alteration of free fraction of the drugs due to plasma protein changes in renal impairment, hepatic impairment, or pregnancy. However, the prodrugs' instability in human plasma presents a challenge for accurate PPB determination. In this research work, two approaches were used in the method development and qualification for PPB assessment of RDV and TAF. For RDV, dichlorvos was used to inhibit esterase activity to stabilize the prodrug in plasma during equilibrium dialysis (ED). The impact of dichlorvos on protein binding was evaluated and determined to be insignificant by comparing the unbound fraction (fu) determined by the ED method with dichlorvos present and the fu determined by an ultrafiltration method without dichlorvos. In contrast to RDV, TAF degradation in plasma is ∼3-fold slower, and TAF stability cannot be improved by dichlorvos. Fit-for-purpose acceptance criteria for the TAF PPB method were chosen, and an ED method was developed based on these criteria. These two methods were then qualified and applied for PPB determinations in clinical studies.


Sujet(s)
AMP/analogues et dérivés , Alanine/analogues et dérivés , Agents antiVIH , Infections à VIH , Promédicaments , Humains , Ténofovir , Agents antiVIH/usage thérapeutique , Liaison aux protéines , Promédicaments/métabolisme , Dichlorvos/usage thérapeutique , Adénine , Protéines du sang/métabolisme , Infections à VIH/traitement médicamenteux
17.
Article de Chinois | MEDLINE | ID: mdl-37667164

RÉSUMÉ

Severe acute dichlorvos poisoning is characterized by rapid onset, swift disease progression and serious complications. It frequently involves multiple organ failure (central, respiratory and circulatory systems), severe acidosis, and rare occurrences of gastric perforation. When secondary gastric perforation occurs, treatment becomes difficult and the prognosis of patients is poor. Thus, early and sufficient gastrointestinal decontamination is crucial. This article presented two cases of gastric perforation secondary to dichlorvos poisoning and discussed the causes of gastric perforation, as well is clinical diagnostic and treatment methods.


Sujet(s)
Dichlorvos , Défaillance multiviscérale , Humains
18.
Luminescence ; 38(11): 1872-1882, 2023 Nov.
Article de Anglais | MEDLINE | ID: mdl-37555766

RÉSUMÉ

In this work, a facile one-step green synthesis was developed for the fabrication of blue fluorescent copper nanocluster (Brahmi-CuNCs) from the extract of Bacopa monnieri (common name is Brahmi) via a microwave method. The as-prepared Brahmi-CuNCs emitted blue fluorescence at 452 nm when excited at 352 nm and showed a quantum yield of 31.32%. Brahmi-derived blue fluorescent CuNCs acted as a probe for fluorescence sensing of dichlorvos. Upon the addition of dichlorvos, the blue emission for Brahmi-CuNCs was gradually turned off, favouring establishment of a calibration graph in the range 0.5-100 µM with a detection limit of 0.23 µM. The as-synthesized Brahmi-CuNCs exhibited marked sensitivity and selectivity towards dichlorvos, favourable for assaying dichlorvos in various samples (cabbage, apple juice, and rice).


Sujet(s)
Bacopa , Nanoparticules métalliques , Fluorescence , Cuivre , Dichlorvos , Spectrométrie de fluorescence/méthodes , Colorants fluorescents , Limite de détection
19.
Front Toxicol ; 5: 1207612, 2023.
Article de Anglais | MEDLINE | ID: mdl-37469457

RÉSUMÉ

Organophosphate pesticides are widely used in agriculture, leading to soil, water, and food contamination. Among these compounds is Dichlorvos [O,O-dimethyl O-(2,2-dichlorovinyl)phosphate, DDVP], which is listed as a highly toxic compound by the Environmental Protection Agency and World Health Organization. Exposure to DDVP can result in nervous, respiratory, hepatic, and reproductive abnormalities, in addition to endocrine disrupting, mutagenic, and carcinogenic effects. Little is known about the impacts of DDVP on the reprogramming of lipid metabolism, which is also associated with the development and progression of cancer, since the tumor cells need to recruit, capture, and use fatty acids to compose their building membranes. This study aimed to evaluate the influence of the pesticide DDVP on lipid metabolism in the prostate, after chemical induction by the carcinogen N-methyl-N-nitrosourea (MNU). For this, 32 Fischer rats aged 90 days were randomly divided into four experimental groups: Control, DDVP, MNU, and MNU + DDVP. The MNU and MNU + DDVP groups underwent chemical induction with MNU (15 mg/kg) and the DDVP and MNU + DDVP groups received a diet supplemented with DDVP (10 mg/kg). Histopathological analyses of the rat ventral prostate showed 100% incidence of epithelial hyperplasia in the MNU and MNU + DDVP groups. This finding was accompanied by an increase of the epithelial compartment in the MNU + DDVP group. Immunolocalization of important proteins linked to lipid metabolism has been established. In the MNU + DDVP group, Western blotting analyses pointed out an increased expression of the protein LIMP II (Lysosomal Integral Membrane Protein-II), which is correlated with the capture and distribution of lipids in tumor cells. Together, these results indicate that the association of a low dose of DDVP with MNU was able to promote alterations in the morphology and lipid metabolism of the rat ventral prostate, which may be related to tumor progression in this organ.

20.
An Bras Dermatol ; 98(5): 644-650, 2023.
Article de Anglais | MEDLINE | ID: mdl-37208226

RÉSUMÉ

BACKGROUND: Pesticides, mainly organophosphates (OP), have been related to increased risk of pemphigus vulgaris (PV) and pemphigus foliaceus (PF), nevertheless, their measurement has not been determined in pemphigus patients. OBJECTIVE: To evaluate pesticide exposure and pesticide measurement, comparing PV, PF and control groups in Southeastern Brazil. METHODS: Information about urban or rural residency and exposure to pesticides at the onset of pemphigus was assessed by questionnaire interview; hair samples from the scalp of PV, PF, and controls were tested for OP and organochlorines (OC) by gas-phase chromatography coupled to mass spectrometry. RESULTS: The minority of PV (2 [7.1%] of 28) and PF (7 [18%] of 39), but none of the 48 controls, informed living in rural areas at the onset of pemphigus (p = 0.2853). PV (33.3%), PF (38.5%), and controls (20%) informed exposure to pesticides (p = 0.186). Twenty-one (14.8%) of 142 individuals tested positive for OP and/or OC: PV (2 [6.3%] of 32) and PF (11 [25.6%] of 43) had similar pesticides contamination as controls (8 [11.9%] of 67) (p = 0.4928; p = 0.0753, respectively), but PF presented higher contamination than PV (p = 0.034). PV did not present any positivity for OP. Three (7%) PF tested positive for both OP and OC. Some PF tested positive for three or four OP, mainly diazinon and dichlorvos. STUDY LIMITATION: Lack of data for some controls. CONCLUSION: Although the frequency of PV and PF patients exposed to pesticides was similar, pesticides were more frequently detected in hair samples from PF compared to PV. The cause-effect relationship still needs to be determined.


Sujet(s)
Pemphigus , Pesticides , Humains , Brésil , Pesticides/effets indésirables , Dichlorvos , Poils
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