Acute Organophosphate Toxicity Research Articles

Comparative Analysis of Outcomes in Acute Organophosphate Poisoning With and Without N-acetyl Cysteine Intervention.

Organophosphorus poisoning (OPP) stands as a significant health concern in numerous regions, especially in developing nations. Despite the rising complexities and case fatalities associated with exposure, the treatment approach has remained unchanged for many years. Based on clinical insights, certain pharmacologic agents have demonstrated utility in enhancing outcomes and reducing complications arising from this type of exposure. The objective of this study is to compare the outcome of N-acetyl cysteine in the treatment of acute organophosphate poisoning cases. In terms of a) its impact on the requirement of atropine, b) Length of hospital stay, and mortality. The study was conducted in the intensive care unit (ICU) of the General Hospital Lahore. Thirty patients with a history and clinical presentation indicative of acute organophosphorus poisoning were randomly divided into two groups in a 1:1 ratio. The treatment group received parenteral administration of atropine, pralidoxime, and N-acetylcysteine (NAC) as an adjuvant, and the control group received standard treatment for acute organophosphate (OP) toxicity. Throughout the study duration, 30 patients suffering acute organophosphate (OP) toxicity (14 men, 16 women) were examined, with an age mean of (25.83±11.59) years. In the interventional group, only four patients required ICU admission, but in the control group, eight patients were admitted to ICU. The correlation result between the dose of atropine and length of hospital stays was not statistically significant between both study groups (<0.005). Plasma Cholinesterase (PChE) level (KU L-1) and total dose of Pralidoxime (g) were statistically significant in the length of hospital stay. The data was not normally distributed, so the non-parametric tests were applied. The Wilcoxon ranked test showed significant improvement in both the controlled and interventional groups because the p-value was (<0.005). Intergroup comparison analyzed by using the Mann-Whitney U test showed a significant reduction in the severity and other associated symptoms in the interventional group because the p-value was (0.001). The outcome demonstrated that the NAC group had a decreased demand for atropine rather than Pralidoxime. In the NAC group, the length of hospital stay and mortality was decreased. The administration of NAC to the present study procedure for acute organophosphate (OP) poisoning is suggested.

Oxidative stress response biomarker gene expression in Piaractus brachypomus (Characiformes: Serrasalmidae)

ABSTRACT Oxidative stress may occur in the fish brain under several conditions, including tissue reoxygenation during anaesthesia, injury and toxic exposure. An imbalance in oxidative homeostasis can lead to oxidative stress, triggering several adaptive mechanisms at both the genetic and protein levels. The aim of this study was to assess the transcription levels of five oxidative stress-related genes in the Colombian native fish red-bellied pacu, Piaractus brachypomus, under anaesthesia with menthol (50 mg/L) and eugenol (40 mg/L), as well as in models of acute brain injury and organophosphate toxicity. Relative gene expression was assessed in the brain, gill and liver tissues of fish under anaesthesia and in the brain tissues of fish in the brain injury and toxicity experiments. It was found that glutathione reductase (GSR) mRNA levels in the brain were significantly higher in the eugenol group than in the menthol group, ATP synthase subunit 6 (ATP6) transcription was downregulated after brain injury, and the GSR, ATP6 and superoxide dismutase 2 (SOD2) genes were upregulated in fish exposed to the organophosphate chlorpyrifos. This is the first evaluation of the relative gene expression of oxidative response biomarkers in P. brachypomus.

Differential Impact of Severity and Duration of Status Epilepticus, Medical Countermeasures, and a Disease-Modifier, Saracatinib, on Brain Regions in the Rat Diisopropylfluorophosphate Model.

Acute organophosphate (OP) toxicity poses a significant threat to both military and civilian personnel as it can lead to a variety of cholinergic symptoms including the development of status epilepticus (SE). Depending on its severity, SE can lead to a spectrum of neurological changes including neuroinflammation and neurodegeneration. In this study, we determined the impact of SE severity and duration on disease promoting parameters such as gliosis and neurodegeneration and the efficacy of a disease modifier, saracatinib (AZD0530), a Src/Fyn tyrosine kinase inhibitor. Animals were exposed to 4 mg/kg diisopropylfluorophosphate (DFP, s.c.) followed by medical countermeasures. We had five experimental groups: controls (no DFP), animals with no continuous convulsive seizures (CS), animals with ∼20-min continuous CS, 31-60-min continuous CS, and > 60-min continuous CS. These groups were then assessed for astrogliosis, microgliosis, and neurodegeneration 8 days after DFP exposure. The 31-60-min and > 60-min groups, but not ∼20-min group, had significantly upregulated gliosis and neurodegeneration in the hippocampus compared to controls. In the piriform cortex and amygdala, however, all three continuous CS groups had significant upregulation in both gliosis and neurodegeneration. In a separate cohort of animals that had ∼20 and > 60-min of continuous CS, we administered saracatinib for 7 days beginning three hours after DFP. There was bodyweight loss and mortality irrespective of the initial SE severity and duration. However, in survived animals, saracatinib prevented spontaneous recurrent seizures (SRS) during the first week in both severity groups. In the ∼20-min CS group, compared to the vehicle, saracatinib significantly reduced neurodegeneration in the piriform cortex and amygdala. There were no significant differences in the measured parameters between the naïve control and saracatinib on its own (without DFP) groups. Overall, this study demonstrates the differential effects of the initial SE severity and duration on the localization of gliosis and neurodegeneration. We have also demonstrated the disease-modifying potential of saracatinib. However, its’ dosing regimen should be optimized based on initial severity and duration of CS during SE to maximize therapeutic effects and minimize toxicity in the DFP model as well as in other OP models such as soman.

Glycemic status as a predictor for the outcomes in patients with acute organophosphorus pesticides poisoning

Acute organophosphate (OP) toxicity is a major health problem in different populations. Nearly three million cases are affected annually all over the world. The most common clinical presentations include muscarinic, nicotinic and central nervous system manifestations resulting from cholinergic overload. Nevertheless, endocrine toxicity and affection of glucose homeostasis are reported. The current study aimed to study random blood sugar (RBS) as a simple, inexpensive tool to predict mortality and major outcome events in acute organophosphate poisonings. Ninety adult patients with acute organophosphate poisoning were included in the study. Patients already known to be diabetic before exposure and those with mixed intoxication were excluded. RBS was done to all included patients on admission before receiving any medications. Patients were categorized into euglycemics (62.2%), hyperglycemic (28.9%) and hypoglycemics (8.9%). The severity of organophosphorus poisoning symptoms and signs was graded into; Mild (32.2%), Moderate (38.9%) and Severe (28.9%) grades with a statistically significant association between RBS and poisoning severity at the time of admission. In addition, RBS showed a statistically significant association with each of serum cholinesterase levels, the delay time before hospital admission, the need for intubation, mechanical ventilation and death. Meanwhile, RBS had no statistically significant association with either doses of atropine & toxogonine nor the duration of hospital stay.

Corrected QT Interval as a Predictor of Outcomes in Acute Organophosphate Poisoning Cases

Introduction: Acute organophosphate (OP) poisoning is a global health problem and responsible for many deaths worldwide every year. It acts by inhibition of acetylcholinesterase causing cholinergic crises that lead to muscarinic, nicotinic and central manifestations. One of the most serious complications of organophosphate exposure is cardiac toxicity including electrocardiogram changes.This study aimed to evaluate corrected QT interval as predictor of major outcome events which included mortality, need for mechanical ventilation, number of atropine and toxogonine ampoules and duration of hospital stay in acute organophosphate toxicity. Methods: The study recruited 98 patients suffering from acute OP poisoning, who were admitted to Tanta University Poison Control Unit. QTc interval length and the different outcomes of the patients were recorded. Results: Fifty five patients (56.1 %) showed a prolonged QTc interval. Significant statistical association was recorded between QTc interval and delay time, manner & route of poisoning, severity of oranophosphrous toxicity and pseudocholinesterase level. Also, significant statistical association was recorded between QTc interval and need for mechanical ventilation, mortality, number of atropine & toxogonine ampoules and duration of hospital stay. Conclusion: Finally, it was concluded that QTc interval could be a good predictor for outcomes of acute organophosphrous poisoning.

Effect of Obidoxime Therapy on Cholinesterase Enzymes' Reactivation in Clinically Diagnosed Patients With Acute Organophosphate Toxicity

Organophosphorus poisoning has significant clinical importance, especially in the developing countries, due to its major health consequences. The study evaluated role of obidoxime in reactivation of cholinesterase (ACHE, BuCHE) enzymes in acute organophosphorus (OP) intoxicated patients. It was conducted on group I: 50 patients received obidoxime therapy after acute OP intoxication, and group II: 50 patients did not receive obidoxime. Patients were subjected to neurological evaluation, determination of ACHE and BuCHE levels. Results revealed that there were statistically significant differences between both groups regarding clinical outcomes, with variability of significance regarding initial and final levels of cholinesterase enzymes. It was concluded that BuCHE enzymes' levels can be considered sensitive biomarker for OP exposure and severity, while, ACHE activity reflected the recovery.

Similar Active Sites and Mechanisms Do Not Lead to Cross-Promiscuity in Organophosphate Hydrolysis: Implications for Biotherapeutic Engineering.

Organophosphate hydrolases are proficient catalysts of the breakdown of neurotoxic organophosphates and have great potential as both biotherapeutics for treating acute organophosphate toxicity and as bioremediation agents. However, proficient organophosphatases such as serum paraoxonase 1 (PON1) and the organophosphate-hydrolyzing lactonase SsoPox are unable to hydrolyze bulkyorganophosphates with challenging leaving groups such as diisopropyl fluorophosphate (DFP) or venomous agent X, creating a major challenge for enzyme design. Curiously, despite their mutually exclusive substrate specificities, PON1 and diisopropyl fluorophosphatase (DFPase) have essentially identical active sites and tertiary structures. In the present work, we use empirical valence bond simulations to probe the catalytic mechanism of DFPase as well as temperature, pH, and mutational effects, demonstrating that DFPase and PON1 also likely utilize identical catalytic mechanisms to hydrolyze their respective substrates. However, detailed examination of both static structures and dynamical simulations demonstrates subtle but significant differences in the electrostatic properties and solvent penetration of the two active sites and, most critically, the role of residues that make no direct contact with either substrate in acting as “specificity switches” between the two enzymes. Specifically, we demonstrate that key residues that are structurally and functionally critical for the paraoxonase activity of PON1 prevent it from being able to hydrolyze DFP with its fluoride leaving group. These insights expand our understanding of the drivers of the evolution of divergent substrate specificity in enzymes with identical active sites and guide the future design of organophosphate hydrolases that hydrolyze compounds with challenging leaving groups.

Evaluation of the potential cardiotoxic effects in acute organophosphate toxicity as a prognostic factor

Background/aim Organophosphorus compounds are the most commonly used pesticides as a result of their easy availability. They are highly toxic compounds for human beings. The study aimed to evaluate the potential cardiotoxic effects in acute organophosphate toxicity as a prognostic factor. Patients and methods This study was carried out on 48 organophosphate acutely intoxicated adult patients. All participants were subjected to the following: sociodemographic study, patient’s history, clinical examination, laboratory investigations, ECG (ECG changes were graded as minor, moderate, and severe), and echocardiography. Results Regarding acute organophosphorus poisoning (OPP) severity, patients with mild, moderate, and severe intoxication represented 18.6, 35.4, and 45.8 of the studied patients, respectively. Of acute OPP patients, 81.25% had abnormal ECG with ischemic changes in 66.7% of patients and arrhythmia in 43.6%. Inverted T-wave and elevated ST segment were the most frequent among ischemic findings while atrial fibrillation was the most frequent arrhythmic finding. The ECG changes induced by acute OPP were graded as moderate in 68.75% of patients and severe in 12.5%. Only one case of acute OPP was diagnosed as acute myocardial infarction. No cases with minor ECG grading were recorded. There was a statistically significant difference between acute OPP severity and ECG grading. Patients with acute OPP have shown a mean QTc interval of 0.46±0.062 s. In all, 47.9% of patients reported prolonged QTc interval. QTc interval was significantly more prolonged in severely intoxicated patients. Conclusion ECG grading and corrected QT interval are a predictor for both primary and major outcome in patients with acute OPP.

Prediction of Acute Organophosphate Poisoning Using Glasgow Coma Sale, Serum Cholinesterase and S100B

Background: organophosphate (OP) poisoning is a major health problem worldwide, especially in developing countries, with millions of cases and hundreds thousands of deaths occurring each year. The aim of this study: was to evaluate the role of Glasgow Coma Sale (GCS), serum cholinesterase (SChE) and S100B protein levels in evaluation and prediction of outcome of patients with acute organophosphate poisoning. Material and methods: the present study was conducted on admitted patients with acute organophosphate poisoning in Tanta Toxicological Unit, Tanta University Hospital during the period from the start of July 2014 to the end of June 2015. For all patients; personal and toxicological history, complete clinical examination and measurement of SChE and S100B at admission and after 24hrs were performed for every patient. Outcome assessment; the patients were divided into two groups; group (1) included patients who survived and group (2) included patients who died. Results: the present study was carried out on 24 patients with acute severe organophosphate toxicity, their age ranged from 16-48 years. Sixteen patients (66.67%) were survived and eight (33.3%) were died. About two third of the patients were female (66.67%), half of them were students (50%) and took malathion (50%). All patients took organophosphates orally and in a suicidal attempt. The GCS was higher in survived patients (6-11) than died ones (3-5). Additionally, serum S100B level at both admission and after 24hrs, revealed significant increase in its level in died patients than survived. While, SChE showed non-significant decrease in both survived and died patients. SChE and S100B at both admission and after 24hrs cannot predict mortality. However, GCS can predict mortality with 100% sensitivity and 75% specificity at a cut off level of 9. Conclusion: both GCS and S100B had significant correlation with the patients’ outcome. Inspite of that, only GCS can predict mortality in 100% of the patients who has a GCS equal to or lower than 9. Also, 75% of survivors had GCS above this cut off value.

EFFECT OF INTRAVENOUS MAGNESIUM SULPHATE ON MORTALITY RATE IN ACUTE ORGANOPHOSPHATE TOXICITY

organophosphates are widely used in agriculture as pesticides, in industry and as household chemicals, allowing many opportunities for acute poisoning, as well as for occupational use. Besides, organophosphates being nerve agents are used in military setting or in terrorist attacks. Fifty years after first use, we still do not know what the optimum treatment for organophosphate toxicity is. Small studies suggest benefit from new treatments such as magnesium sulphate, but much larger trials are needed. The aim of the study was to evaluate the effect of i.v. Magnesium sulphate on mortality rate in acute organophosphate toxicity. Patients and methods: a comparative study in which iv magnesium sulphate was given in a dose of 1g/6hrs for 24hrs to 50 patients acutely intoxicated with organophosphate who are treated with atropine and oximes (group i) and compared to 50 patients who are not given iv magnesium sulphate who are treated with atropine and oximes then mortality rate in the two groups are compared. Results: comparison between the control and the group which took magnesium sulphate showed a statistical significant difference between the 2 groups in the mortality rate (p<0.05). Conclusion: magnesium sulphate decreases mortality rate in acute organophosphate toxicity .such information may in turn guide clinical practice to the use of magnesium sulphate in acute organophosphate toxicity and so more studies should be done to confirm these findings

EFFECT OF INTRAVENOUS MAGNESIUM SULPHATE ON ATROPINE AND OXIME USAGE IN ACUTE ORGANOPHOSPHATE TOXICITY

organophosphates are widely used in agriculture as pesticides, in industry as softening agents and additives to lubricants. They are also used as household chemicals, allowing many opportunities for acute poisoning, as well as for occupational use. Besides, organophosphates being nerve agents are used in military setting or in terrorist attacks. Organophosphates self-poisoning is an important clinical problem in rural regions of the developing world, and kills an estimated 200 000 people every year. Unintentional poisoning kills far fewer people but is a problem in places where highly toxic organophosphates pesticides are available. Patients and methods: a comparative study in which iv magnesium sulphate was given in a dose of 1g/6 hrs for 24 hrs to 50 patients acutely intoxicated with organophosphate who are treated with atropine and oximes (group i) and compared to 50 patients who are not given iv magnesium sulphate who are treated with atropine and oximes then atropine use and oxime use in the two groups are compared. Results: comparison between the control and the group which took magnesium sulphate showed a statistical significant difference between the 2 groups in the atropine and the oxime use (p<0.05). Conclusion: magnesium sulphate decreases atropine and oxime use in acute organophosphate toxicity. Such information may in turn guide clinical practice to the use of magnesium sulphate in acute organophosphate toxicity and so more studies should be done to confirm these findings

Effects of Chlorpyrifos and Chlorpyrifos-Oxon on the Dynamics and Movement of Mitochondria in Rat Cortical Neurons

Organophosphate (OP)-based pesticides have been used extensively for decades, and as a result, they have become almost ubiquitous in our environment. There is clinical and animal evidence to suggest that chronic exposures to OPs can lead to cognitive dysfunction and other neurological abnormalities, although the mechanism for these effects is unknown. We previously reported that repeated, subthreshold exposures (defined as doses not associated with signs of acute toxicity) to the commonly used OP chlorpyrifos (CPF) resulted in protracted impairments in the performance of attention and memory-related tasks in rodents as well as deficits in axonal transport ex vivo (in the sciatic nerve). Here, we investigated the effects of CPF and its active metabolite CPF oxon (CPO) on the dynamics and movement of mitochondria in rat primary cortical neurons using time-lapse imaging techniques. Exposure to CPF (1.0-20.0 μM) or CPO (5.0 nM-20.0 μM) for 1 or 24 h resulted in a concentration-dependent increase in mitochondrial length, a decrease in mitochondrial number (indicative of increased fusion events), and a decrease in their movement in axons. The changes occurred at concentrations of CPF and CPO that did not inhibit acetylcholinesterase activity (the commonly cited mechanism of acute OP toxicity), and they were not blocked by cholinergic receptor antagonists. Furthermore, the changes did not seem to be associated with direct (OP-related) effects on mitochondrial viability or function (i.e., mitochondrial membrane potential or ATP production). The results suggest that an underlying mechanism of organophosphate-based deficits in cognitive function might involve alterations in mitochondrial dynamics and/or their transport in axons.

The effects of vitamin E on the erythrocyte and heart tissue cholinesterase, NO and MDA levels in the acute organophosphate toxicity

The effects of vitamin E on the erythrocyte and heart tissue cholinesterase, NO and MDA levels in the acute organophosphate toxicity

The effects of N-acetylcysteine on the erythrocyte and lung tissue cholinesterase, nitric oxide and malondialdehyde levels in acute organophosphate toxicity

The effects of N-acetylcysteine on the erythrocyte and lung tissue cholinesterase, nitric oxide and malondialdehyde levels in acute organophosphate toxicity

The effects of melatonin on erythrocyte and renal tissue cholinesterase, nitric oxide and MDA levels in acute organophosphate toxicity

The effects of melatonin on erythrocyte and renal tissue cholinesterase, nitric oxide and MDA levels in acute organophosphate toxicity

The effects of CoQ10 on the erythrocyte and liver tissue cholinesterase, NO and MDA levels in the acute organophosphate toxicity

The effects of CoQ10 on the erythrocyte and liver tissue cholinesterase, NO and MDA levels in the acute organophosphate toxicity

The effects of melatonin on erythrocyte and brain cholinesterase, nitric oxide and MDA levels in acute organophosphate toxicity

The effects of melatonin on erythrocyte and brain cholinesterase, nitric oxide and MDA levels in acute organophosphate toxicity

Effects of N-acetylcysteine on the erythrocyte and liver cholinesterase, nitric oxide and malondialdehyde levels in acute organophosphate toxicity

The aim of this study was to investigate the effects of N-acetylcysteine (NAC) on the levels of erythrocyte and liver cholinesterase (CE), nitric oxide (NO) and malondialdehyde (MDA) in acute organophosphate poisoning (AOP) and to compare with pralidoxime (PAM)-atropine treatment.

Effects of CoQ10 on the erythrocyte and heart tissue cholinesterase, nitric oxide and malondialdehyde levels in acute organophosphate toxicity

The aim of this study was to examine the effects of CoQ10 on malondialdehyde (MDA) and nitric oxide (NO) levels and on the choline esterase (CE) activity in the heart tissue and erythrocytes in acute organophosphate poisoning (AOP) and to compare it with antidote treatment.

The favorable effects of vitamin E added on treatment of experimental acute organophosphate toxicity

The favorable effects of vitamin E added on treatment of experimental acute organophosphate toxicity