Paraoxonase-1 Pseudo Cholinesterase Organophosphate Toxicity Enzyme in Prediction the Severity and Outcome of Acute Organophosphate Poisoning and Its Correlation With Pseudo Cholinesterase Enzyme Level.

Organophosphate Poisoning Clinical Trial

Official title:

A Prospective Study on the Role of Paraoxonase-1 Enzyme in Prediction the Severity and Outcome of Acute Organophosphate Poisoning and Its Correlation With Pseudo Cholinesterase Enzyme Level.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06108557
• Other study ID #: Soh-Med-23-10-14MD
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 2024
• Est. completion date: August 2025

Study information

• Verified date: October 2023
• Source: Sohag University
• Contact: alaa M abd elgwad, assistant lecutrer
• Phone: 01095929540
• Email: alaa_mohamed[@]med.edu.eg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the present study is to:

Evaluate the serum Paraoxonase-1 level in cases with organophosphate compounds poisoning and to correlate it᾿s level with the severity, outcome of acutely organophosphate poisoned cases .

Evaluate the serum pseudocholinestrase level in cases with organophosphate compounds poisoning and to correlate it with the Paraoxonase-1 level in those cases.

Description:

Pesticides refer to a wide range of chemicals that are employed to increase agricultural output. Several pesticides have been shown to have severe negative impacts on human health, including acute toxicity (accidental poisoning deaths, particularly in impoverished nations) and chronic toxicity (even at low concentrations) (Trellu et al., 2021).

In the central nervous system of mammals and insects, organophosphate compounds (OPC) inhibit acetylcholinesterase irreversibly by inhibiting acetylcholine breakdown during nerve impulse transmission. Continuous neuronal excitation causes a variety of hazardous symptoms, including slow heart rate, pinpoint pupils, and seizures and respiratory failure (RF) which is the leading cause of morbidity and fatality (Zhai et al., 2021).

The diagnosis of acute organophosphate poisoning is based on the individual's medical history, physical examinations, and toxidromes of acute poisoning. Predicting the severity, prognosis, and complications related to poisoning requires a variety of clinical observations, electrocardiography, and blood or urine sample results. Electrolytes, the complete blood count, and arterial blood gas are virtually always tested (Kim et al., 2022).

Research started to focus on Paraoxonase-1 enzyme after terrorists released sarin in a Tokyo subway in 1995, which resulted in several deaths (La Du, 1996 ). Scientists searched for a potent enzyme for the rapid clearance of nerve agents (Josse et al., 2001).

Paraoxonase-1 (PON1) is an esterase that protects low-density lipoproteins from oxidation and detoxifies organophosphates and nerve agents. Paraoxonase-1 is predominantly produced in the liver, although enzyme activity has been detected in the kidney and brain (Schomaker et al., 2013).

They are found in a variety of tissues and are mostly linked to cell membranes and certain lipoproteins, while a free enzyme has been discovered in the blood (Reichert et al., 2021).

Initial baseline data suggests that Paraoxonase-1 varies among healthy people. Paraoxonase-1 exhibits broad range of specificity, affinity and different rates of hydrolysis for organophosphate compounds (Li et al., 2000).

Levels of plasma Paraoxonase-1 can vary tremendously, due to the polymorphisms in the promoter region of Paraoxonase-1 gene (Furlong, 2007).

Human serum Paraoxonase-1 hydrolyzes organophosphate compounds and so may significantly alters an individual᾿s susceptibility to the toxicity of these chemicals (Richard et al., 2013).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 90
• Est. completion date: August 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 7 Years and older

Eligibility

Inclusion Criteria:

According to Patil (2014)'s recommendations, the following criteria are used to make the diagnosis of OPC poisoning:

Previous OPC exposure. The cholinergic toxidrome-specific features of OPC toxicity. After using atropine, muscarinic symptoms and signs improved. low pseudo-cholinesterase activity in serum.

Exclusion Criteria:

Cases under the age of 7. Asymptomatic cases. cases who have a history of severe renal, cardiac, pulmonary, or nephritic syndrome.

cases with any of the following conditions which reduce pseudocholinesterase activity:

cases who have a history of parenchymal liver disease, acute infection, metastatic cancer, malnutrition, iron deficiency anemia, or dermatomyositis.

cases who are pregnant or who are using narcotics or poisonous substances (such as cocaine, carbon disulfide, benzalkonium salts, organic mercury compounds, ciguatoxins, and solanines) (oral contraceptive pills and metoclopramide).

Related Conditions & MeSH terms

• Organophosphate Poisoning
• Poisoning

Intervention

Diagnostic Test:
• Serum Pararoxonase -1 level
The individual's venous blood will be taken five milliliters under strict aseptic conditions of both control and case groups (before antidotal therapy). Then the blood will be left to be coagulated for 10-20 minutes at room temperature, then centrifugation will be done by laboratory centrifuge. Serum samples were obtained, then half of the separated serum will be used for pseudocholinesterase enzyme assay and the other one will be used for Paraoxanase-1 (PON-1) analysis . Serum PON-1: The enzyme-linked immunosorbent assay (ELISA) will be used to measure it using human Pararoxonase (PON) ELISA kits. Serum pseudocholinesterase: is based on spectrophotometric measurement.
• Diagnostic Test: Serum pseudocholinesterase enzyme level
The individual's venous blood will be taken five milliliters under strict aseptic conditions of both control and case groups (before antidotal therapy). Then the blood will be left to be coagulated for 10-20 minutes at room temperature, then centrifugation will be done by laboratory centrifuge. Serum samples were obtained, then half of the separated serum will be used for pseudocholinesterase enzyme assay and the other one will be used for Paraoxanase-1 (PON-1) analysis . Serum PON-1: The enzyme-linked immunosorbent assay (ELISA) will be used to measure it using human Pararoxonase (PON) ELISA kits. Serum pseudocholinesterase: is based on spectrophotometric measurement.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sohag University

References & Publications (4)

Furlong CE. Genetic variability in the cytochrome P450-paraoxonase 1 (PON1) pathway for detoxication of organophosphorus compounds. J Biochem Mol Toxicol. 2007;21(4):197-205. doi: 10.1002/jbt.20181. Erratum In: J Biochem Mol Toxicol. 2007;21(5):323. — View Citation

Josse D, Lockridge O, Xie W, Bartels CF, Schopfer LM, Masson P. The active site of human paraoxonase (PON1). J Appl Toxicol. 2001 Dec;21 Suppl 1:S7-11. doi: 10.1002/jat.789. — View Citation

Kim YO, Kim HI, Jung BK. Pattern of change of C-reactive protein levels and its clinical implication in patients with acute poisoning. SAGE Open Med. 2022 Jan 30;10:20503121211073227. doi: 10.1177/20503121211073227. eCollection 2022. — View Citation

La Du BN. Structural and functional diversity of paraoxonases. Nat Med. 1996 Nov;2(11):1186-7. doi: 10.1038/nm1196-1186. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the serum Paraoxonase-1 level	Evaluate the serum Paraoxonase-1 level in cases with organophosphate compounds poisoning and to correlate it?s level with the severity, outcome of acutely organophosphate poisoned cases .; the individual's venous blood will be taken five milliliters under strict aseptic conditions of both control and case groups (before antidotal therapy). Then the blood will be left to be coagulated for 10-20 minutes at room temperature, then centrifugation will be done by laboratory centrifuge. Serum samples were obtained, then half of the separated serum will be used for pseudocholinesterase enzyme assay and the other one will be used for Paraoxanase-1 (PON-1) analysis .; Serum PON-1: The enzyme-linked immunosorbent assay (ELISA) will be used to measure it using human Pararoxonase (PON) ELISA kits.	18 months
Secondary	Evaluate Serum pseudocholinesterase level	Evaluate the serum pseudocholinestrase level in cases with organophosphate compounds poisoning and to correlate it with the Paraoxonase-1 level in those cases.; Serum pseudocholinesterase: is based on spectrophotometric measurement.	18 months