الفهرس | Only 14 pages are availabe for public view |
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. |