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Abstract
Organophosphate exposure occurs among people who
come into contact with the chemicals as a result of
their occupation and the general population is exposed by
the entry and spread of the chemicals into the environment.
The organophosphate insecticides bind with the
cholinesterase (ChE) enzyme at the neuromuscular junction
and inhibit the activity of the enzyme by irreversible
phosphorylation.
Individuals with specific defects in OP metabolism
might be expected to be at greater risk of toxicity. The
hydrolysis of OP pesticides by serum paraoxonase (PON1)
is a major factor in determining the susceptibility of acute
and chronic OP exposure.
The aim of this study was to study the influence of
the genetic variation of PON1 gene on paraoxonase enzyme
activity in cases of OPP admitted to the PCC, Ain Shams
University Hospitals. In addition to determine its role
among chronically OP exposed farmers from El-Sharkia
Government.
The current work was conducted on 80 adult cases of
both sexes. They were divided into three groups, group I
which was further subdivided into Ia (control for acute
cases) and group Ib (control for chronic cases), group II
included 30 adult patients presented to the Poison Control
Center (PCC), Ain Shams University Hospitals with acute
OPP. Group III which included 30 adult farmers who were
chronically exposed to OPC.
Their personal and medical data, observation,
investigation and treatment were recorded in a special
observation sheet. All the obtained data were statistically
analyzed.
They were subjected to the following:
I- Sociodemographic data: It included data regarding
age, sex, occupation and area of residence.
II- Clinical Evaluation: The mode of poisoning, route of
administration, time lapse between the exposure and
arrival to the PCC were recorded.General examination
and systemic examination including examination of
respiratory system, cardiovascular, neurological and
gastrointestinal systems were examined.
III- Investigational parameters: Every patient was
subjected to ABGs, random blood sugar, serum (sodium
and potassium), pseudocholinesterase, paraoxonase
activity, PON1genotyping, ECG and chest X ray.
The study revealed that the mean age for acutely
intoxicated cases was 30.86 ±11.68 with male to female
ratio 1.3:1. The majority were from urban areas. The mean
age of chronically exposed farmers was 38.13±12.67 with
male to female ratio 1.7:1.
Acute OPP was mostly due to suicidal attempts and the
highest incidence was among unemployed cases.
The respiratory, cardiovascular, neurological and the
digestive systems were affected by different degrees. The
commonest presentation was excessive sweating (63%)
followed by vomiting (60%) and the commonest physical
sign was bronchial hypersecretion (77%).
The serum potassium and serum sodium were
significantly decreased among acute OPP cases. In addition
there was significant increase in random blood sugar level
among them.
Hypoxia, acidosis and hypercarbia were found in cases
with severe acute OPP due to inadequate oxygenation and
ventilation.
Pseudocholinesterase level was significantly decreased
in both acutely and chronically exposed cases to OP.
Polymorphisms in PON1 genotype influenced the
paraoxonase enzyme activity. Individuals having the RR
genotype had higher activity toward paraoxon than QR
genotype while, those with QQ genotype had the least
paraoxonase activity. Regarding PON1 L55M, there was
decrease in mean PON1enzyme activity from LL > LM >
MM genotyp
Moreover, the combined analysis of the two
polymorphisms (PON1-192 and 55) revealed that R carriers
for PON1-192 polymorphism and L carriers for PON1-55
polymorphism showed the highest paraoxonase activity.
On the basis of these data on the correlation between
PON1 activities and the severity of clinical manifestations,
there was an inverse relationship in which highest PON1
activity was found in cases with mild acute OPP
manifestations and vice versa.