Assessment of the Prognostic Value of Nerve Damage Biomarkers in Acute and Chronic Organophosphate Toxicity
Conditions: Neuroinflammatory Response, Nerve Injury, Nerve Damage, Neurotoxicity, Nerve Degeneration, Genotoxicity
Sponsor: Alexandria University

 
Assessment of the prognostic value of 
nerve damage biomarkers in acute and 
chronic organophosphate toxicity 
Study protocol 
 
 
 
JULY 30, 2023 
      
      

  INTRODUCTION 
 
    Organophosphates are among the most easily accessible toxic compounds worldwide. The 
global occurrence of poisoning due to organophosphates is estimated to be 300,000 to 2 million 
cases per year, varying between accidental exposure and suicidal attempts (1,2). Owing to the high 
incidence of exposure, research focused on the detection of the possible mechanisms of toxicity, 
as well as evaluation of various antidote efficacy and biomarkers that can be used as mortality 
predictors. The main mechanism of pesticides toxicity is via inhibition of acetylcholinesterase 
enzyme responsible for the degradation of the neurotransmitter acetylcholine. This abrupt 
increase in acetylcholine levels leads to a cholinergic surge with continuous stimulation of 
receptors leading to the manifestation of signs and symptoms that vary according to the route of 
exposure to organophosphates (3,4). Another suggested mechanism was the oxidative stress 
induced by the pesticides (2). 
However, only few studies focused on biomarkers and their quantitation. Results emphasized the 
importance of detecting the levels of serum cholineesterase as a prognostic indicator for acute 
toxicity (5,6). Nevertheless, it has been shown that the reliability on serum cholinesterase levels is 
controversial (2,7,8). Oxidative stress biomarkers (malondialdehyde (MDA) and total antioxidant 
capacity (TAC)), activity of the apoptotic biomarkers (caspase 3 and caspase 9) and 
pseudocholinesterase (p.ChE) were further investigated as mortality predictors (2). Significantly, 
there is paucity of evidence regarding the value of biomarkers addressing the involvement of nerve 
damage resulting from organophosphate poisoning in acute and chronic toxicities despite the 
accumulating evidence of their chronic neurological impact associated with their action on 
neurotoxic esterase (5,8) 
 
AIM OF THE STUDY 
To assess the possible prognostic value of markers of neuroinflammation and damage by a full 
proteomic and glycomic profile of acute and chronic organophosphate exposure patients. The 
profiling will be generated together with an assessment of their genotoxic effect. This will be 
conducted in parallel to the assessment of traditional markers of inflammation and oxidative stress. 
 
 

 
PLAN OF THE STUDY 
Study setting:  
- 
Acute exposure patients will be recruited from the Poison Center and Emergency 
Department of Alexandria Main University Hospital. 
- 
Chronic exposure patients will be recruited from farm field workers with a confirmed 
history of repeated occupational exposure to organophosphate pesticides. 
- Control subjects will be recruited from city dwellers without any medical conditions 
(healthy subjects) with comparable age and gender. 
 
Study design: 
Type of the trial:  cross-sectional trial 
Inclusion criteria: 
 Chronic Patients:  Adult males with age above 18. 
Acute Patients: Adult males and females with age above 18 .  
Controls: Adult males and females with age above 18 without previous exposure to 
organophosphate pesticides.  
No restrictions on comorbidities in the three groups except those mentioned under Exclusion 
Criteria. 
Exclusion criteria: 
Pediatric patients, patients with neurological diseases (Parkinsonism, epilepsy, Alzheimer’s 
disease , etc. ) and any patient who does not meet the inclusion criteria. 
 
Target population:  
Patients with acute and chronic exposure to organophosphates. 
 
Sample size:  Total number between 60 to 90 patients, divided into three groups:  
1- Controls without previous exposure to organophosphates (n ≥ 15). 
2- Patients with chronic exposure to pesticides (n ≥ 30).  
Patients with acute exposure to organophosphates (n ≥30). 
 

Outcome assessment: 
Identification of a neuroinflammatory biomarker that correlates with neve injury.  
 
Type of sample and method of selection: 
Convenience sample through nonprobability sampling methods 
 
Data collection methods and tools: 
1-Patient demographics and data regarding chronic patients including: 1) history of 
organophosphates exposure 2) compliance to safety instructions during handling of 
pesticides 3) medical history 4) general health status 5) cholinergic symptoms if any will 
be recruited through a questionnaire answered by the patients on the day of recruitment.  
2-Blood sample collection with required preparations for serum extraction. 
3- Laboratory analysis for some biomarkers. 
4-Proteomic and glycomic analysis to identify the biomarker that correlates with nerve 
injury(9). 
 
Ethical consideration: 
1. The researcher will seek the approval of the Ethics Committee of Faculty of Pharmacy & 
Alexandria University for conducting the research. 
2. The researcher will comply with the International Guidelines for Research Ethics for medical 
research involving human subjects for the declaration of Helsinki (10). 
3. The researcher declares that there is no conflict of interest. 
4. All participants will sign an informed consent before being included in the study. 
Statistical analysis: 
The collected data will be subjected to statistical analysis by the use of suitable techniques to 
achieve the objectives of the study. 
 
 
 
 
 

REFERENCES 
1-Syed, S., Gurcoo, S. A., Farooqui, A. K., Nisa, W., Sofi, K., & Wani, T. M. (2015). Is the 
World Health Organization-recommended dose of pralidoxime effective in the treatment of 
organophosphorus poisoning? A randomized, double-blinded and placebo-controlled 
trial. Saudi journal of anaesthesia, 9(1), 49–54. 
https://doi.org/10.4103/1658-354X.146306 
2-Shimaa Tallat, Rania Hussien, Rania Hassan Mohamed, Mahmoud B. Abd El Wahab & 
Magdy Mahmoud(2020). Caspases as prognostic markers and mortality predictors in acute 
organophosphorus poisoning. Journal of Genetic Engineering and Biotechnology (2020) 18:10 
https://doi.org/10.1186/s43141-020-00024-y 
3-Roja 
Rahimi, 
Shekoufeh 
Nikfar 
& 
Mohammad 
Abdollahi 
(2006). 
Increased morbidity and mortality in acute human organophosphate-poisoned patients treated 
by oximes: a meta-analysis of clinical trials. Human & Experimental Toxicology journal (2006) 
25:157-162 
4-Caba, I.-C.; Ștreangă, V.;Dobrin, M.-E.; Jităreanu, C.;Jităreanu, A.; Profire, B.-
S.;Apotrosoaei, M.; Focsa A.-V.; Caba,B.; Agoroaei, L. ClinicalAssessment of 
AcuteOrganophosphorus PesticidePoisoning in Pediatric Patients Admitted to the 
ToxicologyEmergency 
Department. 
Toxics 
2022,10, 
582. 
https://doi.org/10.3390/toxics10100582 
 
5- Neurotoxicity in acute and repeated organophosphate exposure, Sean X. Naughton, Alvin 
V. Terry Jr. Toxicology. 2018 September 01; 408: 101–112. doi:10.1016/j.tox.2018.08.011. 
 
6-Acetylcholinesterase as a Biomarker in Environmental and Occupational Medicine: New 
Insights and Future Perspectives, Maria Giulia Lionetto, Roberto Caricato, BioMed Research 
International Volume 2013, Article ID 321213, 8 pages, http://dx.doi.org/10.1155/2013/321213 
 
7-Review of Biomarkers and Analytical Methods for Organophosphate Pesticides and 
Applicability to Nerve Agents, Jennifer Therkorn, David G. Drewry III. Association of Military 
Surgeons of the United States 2020, Vol. 185, March/April 2020 
 
8-Neuropsychiatric Evaluation in Subjects Chronically Exposed to Organophosphate 
pesticides, Rosane Maria Salvi,* Diogo R. Lara, TOXICOLOGICAL SCIENCES 72, 267–
271 (2003) DOI: 10.1093/toxsci/kfg034, 2003 by the Society of Toxicology 
 
Kobeissy, F.; Kobaisi, A.; Peng, W.; Barsa, C.; Goli, M.; Sibahi, A.; El Hayek, S.; 
-
9
nd Glycoproteomic Techniques in 
Abdelhady, S.; Ali Haidar, M.; Sabra, M.; et al. Glycomic a
Neurodegenerative Disorders and Neurotrauma: Towards Personalized Markers. Cells 2022, 
11, 581. https:// doi.org/10.3390/cells11030581
 
medical 
World Medical Association Declaration of Helsinki: ethical principles for 
-
10
4
-
research involving human subjects. Jama. 2013;310(20):2191