Human Paraoxonase Research Articles

Association of human serum paraoxonase-1 with some respiratory drugs.

In this study, we investigated the effects of certainrespiratory drugs, which are mainly usedon human serum paraoxonase-1 (hPON1; EC 3.1.8.1). hPON1 was purified from human serum, with 354.91 fold and 45% yield by using two simple step procedures including, first, ammonium sulfate precipitation, then, Sepharose-4B-l-tyrosine-1-naphthylamine hydrophobic interaction chromatography. SDS-polyacrylamide gel electrophoresis showed a single protein band belongingto hPON1 with 43 kDa. All the pharmaceutical compounds inhibited the PON1 enzyme highly at the micromolar level. The obtained IC50 values for nine different pharmaceutics ranged from 0.219 μM (salbutamol sulfate) to 67.205 μM (montelukast sodium). So, all drugs couldbe considered as potent hPON1 inhibitors. Ki values and inhibition types were determined by Lineweaver-Burk graphs. While varenicline tartrate and moxifloxacin hydrochloride inhibited the enzyme in a noncompetitive manner, others inhibited it in a mixed manner.

The behaviour of some antihypertension drugs on human serum paraoxonase-1: an important protector enzyme against atherosclerosis.

Paraoxonase-1 (PON1) enzyme is related to high-density lipoprotein (HDL), which is calcium dependent. It has essential roles such as protecting LDL against oxidation and detoxification of highly toxic substances. It is a significant risk to reduce the levels of this enzyme in patients with diabetes mellitus, cardiovascular diseases, hyperthyroidism and chronic renal failure. Here, it was reported that the purification of human serum PON1 using straightforward methods and determination of the interactions between some antihypertension drugs and the enzyme. It was found that these drugs exhibit potential inhibitor properties for human serum PON1 with IC50 values in the range of 131.40-369.40μm and Ki values in the range of 56.24±6.75-286.74±28.28μm. These drugs showed different inhibition mechanisms. It was determined that midodrine and nadolol were exhibited competitive inhibition, but atenolol and pindolol were exhibited non-competitive inhibition. Usage of these drugs would be hazardous in some cases.

Inhibition of paraoxonase 1 by coumarin‐substituted N‐heterocyclic carbene silver(I), ruthenium(II) and palladium(II) complexes

We synthesized three coumarin‐substituted benzimidazolium chlorides and their silver(I), ruthenium(II) and palladium(II) N‐heterocyclic carbene (NHC) complexes. All compounds were characterized using appropriate spectroscopic techniques and elemental analyses. Single‐crystal X‐ray structure of a Pd(II)–NHC complex (6b) was also determined. The inhibitory properties of all compounds were tested on the activity of human paraoxonase 1 (PON1). All complexes exhibited weaker inhibitory properties than their corresponding benzimidazolium salts except for complex 6b which is the most active inhibitor with an IC50 value of 3.01 μM among the compounds reported in this study. A kinetic evaluation showed that this complex inhibits PON1 activity in a non‐competitive manner. Molecular docking studies were also performed for 6b in order to obtain more insight into the binding mode.

Is Human Paraoxonase 1 the Saviour Against the Persistent Threat of Organophosphorus Nerve Agents?

Nerve agents have been used extensively in chemical warfare in the past. However, recent use of Novichok agents have reignited the debate on the threat posed by Organophosphorus Nerve Agents (OPNAs). The currently available therapy for OPNA toxicity is only symptomatic and is potentially ineffective in neutralizing OPNAs. Hence, there is a dire need to develop a prophylactic therapy for counteracting OPNA toxicity. In this regard, human paraoxonase 1 has emerged as the enzyme of choice. In this review, we have focussed upon the recent and past events of OPNA use, their mechanism of action and toxicity. Further, we have emphasized upon the potential of enzyme based therapy and the various advances in the development of paraoxonase 1 as a countermeasure for OPNA poisoning. Finally, we have elaborated the shortcomings of paraoxonase 1 and the work that needs to be undertaken in order to develop human paraoxonase 1 as a prophylactic against OPNA poisoning.

Bazı antrakinonların insan paraoksonaz 1 (hPON1) üzerine etkilerinin incelenmesi

The in vitro effects of the some dihydroxyanthraquinone derivates, anthrorufin, xanthopurpurin, chrysazin and chrysaphanol which are commonly used as anticancer antibiotics, on the activity of purified serum paraoxonase 1 (PON1) (EC 3.1.8.1.) were investigated. Paraoxonase 1 was purified from human blood serum 355,12 fold with 55 % yield with use of ammonium sulphate precipitation and Sepharose-4B-L-tyrozine-1-napthylamine HIC (hydrophobic interaction chromatography) coloumn in return. Sodium Dodecyl Sulphate -polyacrylamide gel electrophoresis (SDS-PAGE) analysis of purified enzyme showed a single band belong to human serum PON1, 43 kDa. The four anthraquinones inhibited PON activity strongly, with IC50 values for anthrorufin, xanthopurpurin, chrysazin and chrysaphanol of 73, 72.25, 75.19 and 105.53 M respectively. Ki constants were determined 34.64, 39.51, 39.73 and 63.59 M, respectively. All anthraquinones showed inhibition in competitive manner.

Serum Paraoxonase-1 (PON1) Activity and Concentration: A new biomarker in Egyptian Patients with Liver Cirrhosis and Hepatocellular Carcinoma

Background and study aim: Hepatoma is the most common cancer worldwide, being regarded as the fifth of all malignancies. Mandating for a new, sensitive and specific markers for HCC are critically needed. Human paraoxonase-1 (PON-1), a Ca+2 dependent esterase in the liver, with antioxidant functions, and binds to the HDL particles and hence discarding carcinogenic lipid radicals as byproduct of lipid peroxidation. The aim of this study was to estimate the importance of serum PON-1 activity and concentration in HCC in Egyptian patients as a more sensitive and specific biomarker compared to an established biomarker; Alpha-fetoprotein (AFP). Patients and Methods: This study was conducted on 88 subjects: 64 patients; 40 patients with HCC, 24 cirrhotic patients and 24 healthy subjects who admitted in Internal Medicine Department, Suez CanalUniversityHospital, Ismailia, Egypt. Clinical and radiological investigations in those of the Cirrhotic, and HCC groups for viral hepatitis markers, liver function tests, serum assay of AFP and PON-1 activity and cconcentrations. Results: The results showed that PON-1 concentration was found significantly lower in HCC patients than those of the control and Cirrhotic group (p<0.001).The sensitivity and specificity of PON-1 concentration for HCC were superior to those of AFP and PON-1 activity especially in recently detected HCC. PON-1 concentration had a sensitivity of 88.3% and specificity of 90.48% at the optimal cut-off value of 70.55 (ng/ml). AFP gives a sensitivity of 82.50% and specificity of 73.08 at a cut-off 20.44 ng/ml. Conclusion: This study demonstrates that PON1 concentration and activity were superior to AFP in the recently detected HCC.

Inhibition Effects of Phenolic Compounds on Human Serum Paraoxonase-1 Enzyme

Metabolic processes in living organisms are closely related to the catalytic activity of enzymes. Inhibition or induction of enzymes leads to toxicities and metabolic interactions. This studyaims to contribute to the growing drug design field by studying PON1-phenolic compound interactions. For this purpose, the paraoxonase-1 enzyme was purified from fresh human serum byusing rapid and different chromatographic techniques. Additionally, it was investigated the inhibitory effects of some phenolic substances on the PON1 and was found that the purified enzyme had themolecular weight of 43 kDa and the specific activity of 3945.15 EU mg-1. These compounds showed potent inhibition against PON1, especially homovanillic acid exhibited a significant inhibition profileagainst PON1 with an IC50 value of 13.84±0.08 mM. Ki constants were 6.10±0.26 mM for homovanillic acid and 16.96±0.76 mM for phloridzin dihydrate. Homovanillic acid had competitiveinhibition while the phloridzin dihydrate inhibited the PON1 as non-competitive. Also, molecular docking computations were performed by using the Glide XP mode. Glide energy of the homovanillicacid determined to be -23.95 kcal mol-1.

Inhibitory Effects of Usnic and Carnosic Acid on Some Metabolic Enzymes: An In vitro Study.

Natural products are produced via primary and secondary metabolism in different organisms. The compounds obtained via secondary metabolism are not essential for the survival of the organism, but they can have a different value for humans. The objective of this study was to examine inhibitory effects of Usnic Acid (UA), a well-known lichen secondary metabolite, and Carnosic Acid (CA), the primary antioxidant compound of Rosmarinus officinalis L., on purified Human Paraoxonase, (PON1), Glutathione Reductase (GR) and Glutathione S-Transferase (GST). These enzymes have antioxidant properties and a protective effect on the oxidation of free radicals. Hence, deficiencies of such enzymes inside cells can result in a buildup of toxic substances and cause some metabolic disorders. UA and CA were tested in various concentrations against human GST, PON1, and GR activity in vitro and they reduced human GST, PON1, and GR activity. UA Ki constants were calculated as 0.012±0.0019, 0.107±0.06 and 0.21±0.1 mM for GST, PON1, and GR enzymes. CA Ki constants were determined as 0.028±0.009, 0.094±0.03 and 0.79±0.33 mM, for GST, PON1, and GR enzymes. UA and CA showed competitive inhibition for GR and GST enzymes, while they exhibited non-competitive inhibition for PON1. These findings indicate that UA and CA could be useful in drug development studies.

The inhibition effects of some sulfonamides on human serum paraoxonase-1 (hPON1).

Paraoxonase 1 (PON1) is an antiatherogenic and organophosphate hydrolyzer enzyme. It has important roles including protecting low density lipoprotein (LDL) against oxidation and the detoxification of highly toxic substances. Reducing the levels of this enzyme in patients with diabetes mellitus, cardiovascular diseases, hyperthyroidism, and chronic renal failure is a major risk. Here, we report on the purification of the human serum PON1 using simple methods and determine the interactions between some sulfonamides and the enzyme. We found that some sulfonamides exhibit potential inhibitor properties for the human serum PON1 with IC50 values in the range of 24.10-201.45 μM and Ki values in the range of 4.41 ± 0.52-150.23 ± 20.73 μM. The sulfonamides showed different inhibition mechanisms. We determined that sulfonamides 1, 2, 4, 5, 8, and 9 showed a non-competitive inhibition effect whereas sulfonamides 3, 6 and 7 showed competitive inhibition. Use of drugs containing the sulfonamides molecule groups with crucial biological activity would be very dangerous in some cases.

32 - Hypobromous acid and loss of cardio-protective paraoxonase-1 activity from human plasma

Paraoxonase-1 (PON1) is a cardio-protective enzyme associated with plasma high-density lipoprotein (HDL). In this study we investigated effects of HOBr, a pro-inflammatory mediator, on plasma PON1 activity. In initial studies, HOBr or HOCl was added to 5-fold diluted human plasma and PON1 phosphotriesterase activity was assayed. Consistent with prior reports, addition of HOCl (2000 uM) to plasma caused loss of PON1 activity, which declined to 71 ± 3 % normal (P 0.05). In conclusion, our results demonstrate HOBr and brominated amines, such as taurine may be important mediators of PON1 activity during inflammation. Supported by Midwestern University.

Effects of static and electromagnetic fields on human serum paraoxonase-1 activity in vitro

Introduction: In recent years the relationship between electromagnetic fields and coronary artery disease is attracted a considerable attention. Low density lipoprotein (LDL) oxidation is the initial step in the development of atherosclerosis. Paraoxonase1 (PON1) protects LDL and High density lipoprotein (HDL) against oxidative processes, thus preventing the formation of atherogenic (oxidized-LDL) ox-LDL molecules. In this study we investigated the effects of static magnetic fields (SMFs) and extremely low frequency electromagnetic fields (ELFEMFs) on PON1 activity as one of the independent risk factors for cardiovascular disease. Materials and methods: Pooled serum sample of 20 healthy men were exposed to SMFs and EMFs flux densities of 0.125, 0.25, 0.5, 1, 2, 3 and 4 mT for 60, 120 and 180 minutes at 25°C and then PON1 activity was measured spectrophotometrically using paraoxon as substrate. Results: EMFs of 0.125-1 mT had no effect on PON1 activity. Exposure to magnetic flux density of 2 mT leads to a significant increase in PON1 activity in 1 hour (P <0.05). Magnetic flux density of 3 and 4 mT, after 1hour of exposure, lead to an increase of PON1 activity to 1.2% and 2.8%, respectively (P <0.01). Conclusion: PON1 activity is influenced by a variety of agents like environmental, pharmacological, and lifestyle factors as well as age and sex. According to the finding of this study ELF-EMFs can alternate the serum activity of PON1 in vitro. If this effect of EMFs on PON1 activity has proven in vivo, it can be considered as an effective factor in coronary artery disease.

Candidate gene polymorphisms related to lipid metabolism in Asian Indians living in Durban, South Africa.

Background & objectives:Asian Indians have been shown to have a high prevalence of metabolic syndrome (MetS), related to insulin resistance and possibly genetic factors. The aim of this study was to determine the genetic patterns associated with MetS in Asian Indians living in Durban, South Africa.Methods:Nine hundred and ninety nine participants from the Phoenix Lifestyle Project underwent clinical, biochemical and genetic assessment. MetS was diagnosed according to the harmonized definition. The apolipoprotein A5 Q139X, lipoprotein lipase (LPL) Hinf I, human paraoxonase 1 (PON1) 192Arg/Gln, cholesteryl ester transfer protein (CETP) Taq1B, adiponectin 45T>G and leptin (LEP) 25CAG were genotyped by real-time polymerase chain reaction in participants with and without MetS. Univariate-unadjusted and multivariate-adjusted relations were conducted for all analyses.Results:The prevalence of MetS was high (49.0%). More females had MetS than males (51.0 vs 42.8%). There was no significant difference in the distribution of genotypes between participants with MetS and those without. Males with the MetS who had the adiponectin TG genotype and human paraoxonase 1 AA genotype were more likely to have reduced high-density lipoprotein cholesterol (HDL-C) (P=0.001) and higher systolic blood pressure (P=0.018), respectively.Interpretation & conclusions:About half of the Asian Indians living in Phoenix had MetS. No association between the polymorphisms studied and the risk for MetS was observed. The adiponectin TG genotype may be associated with reduced HDL-C and the human paraoxonase 1 AA genotype with hypertension in males. This suggested that lifestyle factors were the major determinant for MetS in this ethnic group and the genetic risk might be related to its component risk factors than to MetS as an entity.

Paraoxonase, arylesterase and lactonase activities of paraoxonase-1 (PON1) in obese and severely obese women

Obesity is independently associated with disturbances in lipid and lipoprotein metabolism, oxidative stress, and is a well-established independent risk factor for cardiovascular diseases (CVD). Human paraoxonase 1 (PON1) is a pleotropic high-density lipoprotein (HDL)-associated enzyme with antioxidant and anti-inflammatory proprieties that have been suggested to contribute to the athero-protective function of the lipoprotein. The aim of this study was to investigate whether obesity is associated with PON1 activity and whether this association is influenced by oxidative stress, inflammation and HDL cholesterol (HDL-C) concentration. The promiscuous activities, arylesterase and paraoxonase, and the putative physiological activity, lactonase, of PON1 were assessed in the serum of 214 obese and severely obese, 101 overweight and 129 normal-weight women. Levels of high-sensitivity C-reactive protein (hs-CRP), hydroperoxides (by-products of lipid oxidative damage) and lipid profiles were also evaluated. Arylesterase activity was the only activity that significantly differed across the groups (ANOVA, p < .01), with the greatest decrease observed in individuals with body mass index (BMI) > 40 kg/m2 compared to controls (p < .001). This activity was also inversely, although weakly (r = −0.160, p < .001) correlated with the BMI, and the association was independent of age and levels of oxidative stress and inflammation, but not of HDL-C concentration. In conclusion, our results suggest that the apparent obesity-associated decrement of PON1 activity might simply reflect the decrease in concentration of its plasmatic carrier.

Influence on serum asymmetric dimethylarginine (ADMA) concentrations of human paraoxonase 1 polymorphism (Q192R) and exposure to polycyclic aromatic hydrocarbons (PAHs) in Mexican women, a gene-environment interaction

It has been demonstrated that Cardiovascular Diseases (CVD) are a consequence of the combination of genetic and environmental factors and/or the interaction between them. Therefore, the aim of this study was to evaluate the impact of polycyclic aromatic hydrocarbon (PAHs) exposure and PON1 Q192R polymorphism (genetic susceptibility) on serum asymmetric dimethylarginine (ADMA) levels in Mexican women (n = 206). Urinary 1-hydroxypyrene concentrations (1-OHP; exposure biomarker for PAHs) were quantified using a high-performance liquid chromatography technique, PON1 Q192R polymorphism was genotyped using TaqMan probes and serum ADMA concentrations were evaluated using a commercially available ELISA kit. Urinary 1-OHP levels detected in this study ranged from 0.07 to 9.37 μmol/mol of creatinine (0.13–18.0 μg/g of creatinine). Regarding allele frequency (PON1 Q192R polymorphism), the 192Q-allele frequency was 0.43 and for the 192R-allele it was 0.57. In relation to serum ADMA levels, the levels ranged from 0.06 to 1.46 μmol/L. Moreover, multiple linear regression analysis was performed and associations between urinary 1-OHP levels (β = 0.05, p = 0.002), PON1 Q192R polymorphism (β = 0.04, p = 0.003) and serum ADMA concentrations were found. Besides, an interaction (gene-environment interaction) of both independent variables (1-OHP and PON1 polymorphism) on serum ADMA levels was found (β = 0.04, p = 0.02) in the constructed multiple linear model. Therefore, according to the significance of this research, it is necessary to execute health programs to reduce cardiovascular risk in the assessed population.

The Sweat Metabolome of Screen-Positive Cystic Fibrosis Infants: Revealing Mechanisms beyond Impaired Chloride Transport.

The sweat chloride test remains the gold standard for confirmatory diagnosis of cystic fibrosis (CF) in support of universal newborn screening programs. However, it provides ambiguous results for intermediate sweat chloride cases while not reflecting disease progression when classifying the complex CF disease spectrum given the pleiotropic effects of gene modifiers and environment. Herein we report the first characterization of the sweat metabolome from screen-positive CF infants and identify metabolites associated with disease status that complement sweat chloride testing. Pilocarpine-stimulated sweat specimens were collected independently from two CF clinics, including 50 unaffected infants (e.g., carriers) and 18 confirmed CF cases. Nontargeted metabolite profiling was performed using multisegment injection–capillary electrophoresis–mass spectrometry as a high throughput platform for analysis of polar/ionic metabolites in volume-restricted sweat samples. Amino acids, organic acids, amino acid derivatives, dipeptides, purine derivatives, and unknown exogenous compounds were identified in sweat when using high resolution tandem mass spectrometry, including metabolites associated with affected yet asymptomatic CF infants, such as asparagine and glutamine. Unexpectedly, a metabolite of pilocarpine, used to stimulate sweat secretion, pilocarpic acid, and a plasticizer metabolite from environmental exposure, mono(2-ethylhexyl)phthalic acid, were secreted in the sweat of CF infants at significantly lower concentrations relative to unaffected CF screen-positive controls. These results indicated a deficiency in human paraoxonase, an enzyme unrelated to mutations to the cystic fibrosis transmembrane conductance regulator (CFTR) and impaired chloride transport, which is a nonspecific arylesterase/lactonase known to mediate inflammation, bacterial biofilm formation, and recurrent lung infections in affected CF children later in life. This work sheds new light into the underlying mechanisms of CF pathophysiology as required for new advances in precision medicine of orphan diseases that benefit from early detection and intervention, including new molecular targets for therapeutic intervention.

Assessment of the inhibitory effects and molecular docking of some sulfonamides on human serum paraoxonase 1.

Paraoxonase-1 (PON1) is an organophosphate hydrolyzer and antiatherogenic enzyme. Due to the PON1's crucial functions, inhibitors and activators of PON1 must be known for pharmacological applications. In this study, we investigated the in vitro effects of some sulfonamides compounds on human serum PON1 (hPON1). For this aim, we purified the hPON1 from human serum with high specific activity by using simple chromatographic methods, and after the purification processes, we investigated in vitro interactions between the enzyme and some sulfonamides (2-amino-5-methyl-1,3-benzenedisulfonamide, 2-chloro-4-sülfamoilaniline, 4-amino-3-methylbenzenesulfanilamide, sulfisoxazole, sulfisomidine, and 5-amino-2-methylbenzenesulfonamide). IC50 , Ki values, and inhibition types were calculated for each sulfonamide. 2-amino-5-methyl-1,3-benzenedisulfonamide and 2-chloro-4-sülfamoilaniline exhibited noncompetitive inhibition effect, whereas 4-amino-3-methylbenzenesulfanilamide, sulfisoxazole, and sulfisomidine exhibited mixed type inhibition. On the other hand, 5-amino-2-methylbenzenesulfonamide showed competitive inhibition and so molecular docking studies were performed for this compound in order to assess the probable binding mechanism into the active site of hPON1.

Alzheimer's Disease and Paraoxonase 1 (PON1) Gene Polymorphisms.

Background:Some studies have indicated that human paraoxonase 1 (PON1) activity shows a polymorphic distribution. The aim of this study was to determine the distribution of PON1 polymorphism in patients with Alzheimer’s disease in Gorgan and compare it with a healthy control group.Method:The study included 100 healthy individuals and 50 patients. Enzyme activity and genetic polymorphism of PON1 were determined.Result:There were significant differences in distribution of genotypes and alleles among patients and control group. The most common genotype was CT in patients and control group, while the most frequent alleles were T and C in patients and controls, respectively. There was a statistically significant variation between serum PON1 activity and –108C> T polymorphism. The highest PON1 enzyme activities in the patients and controls were found in CC, while lower enzyme activities were seen in CT and TT genotypes in both genders and age groups.Conclusion:Onset of Alzheimer’s disease may depend on different polymorphisms of the PON1 enzyme. Late or early-onset of Alzheimer’s disease may also depend on age and gender distribution, especially for arylesterase enzyme. Further studies on polymorphism of the enzyme are necessary for interpretation of possible polymorphic effects of enzyme on PON1 activity in humans.

An alternative purification method for human serum paraoxonase 1 and its interaction with methidathion

In this study, an alternative purification method for human Paraoxonase 1 (hPON1) enzyme was developed using two-step procedures, namely ammonium sulphate precipitation and Sepharose-4B-L-tyrosine-1-aminoanthracene hydrophobic interaction chromatography. SDS-polyacrylamide gel electrophoresis of the enzyme indicates a single band with an apparent MW of 43 kDa. The enzyme was purified 674-fold with a yield of 16%. Furthermore, we examined the in vitro effect of methidathion on the enzyme activity to understand the better inhibitory properties of the compound. Methidathion is a highly toxic insecticide used to control a broad spectrum of agricultural insect and mite pests. IC50 value was found to be 0.130 mM for the pesticide. Methidathion showed a competitive inhibition with Ki of 0.119 mM for paraoxon.

Towards Understanding the Catalytic Mechanism of Human Paraoxonase 1: Experimental and In Silico Mutagenesis Studies

Human paraoxonase 1 (h-PON1) is a ~45-kDa serum enzyme that can hydrolyze a variety of substrates, including organophosphate (OP) compounds. It is a potential candidate for the development of antidote against OP poisoning in humans. However, insufficient OP-hydrolyzing activity of native enzyme affirms the urgent need to develop improved variant(s) having enhanced OP-hydrolyzing activity. The crystal structure of h-PON1 remains unsolved, and the molecular details of how the enzyme catalyses hydrolysis of different types of substrates are also not clear. Understanding the molecular details of the catalytic mechanism of h-PON1 is essential to engineer better variant(s) of enzyme. In this study, we have used a random mutagenesis approach to increase the OP-hydrolyzing activity of recombinant h-PON1. The mutants not only showed a 10-340-fold increased OP-hydrolyzing activity against different OP substrates but also exhibited differential lactonase and arylesterase activities. In order to investigate the mechanistic details of the effect of observed mutations on the hydrolytic activities of enzyme, molecular docking studies were performed with selected mutants. The results suggested that the observed mutations permit differential binding of substrate/inhibitor into the enzyme's active site. This may explain differential hydrolytic activities of the enzyme towards different substrates.

Paraoxonase 1 gene polymorphism and enzymatic activity as a prognostic marker in cases of poisoning by cholinesterase inhibitor pesticides among Egyptians

Paraoxonase1 (PON1) is a high-density lipoprotein associated A-esterase capable of hydrolysing activated metabolites (oxons) of several pesticides as organophosphorous, including chlorpyrifos, diazinon as well as carbamates. Human PON1 displays polymorphisms in the coding region (Q192R and L55M) and in the promoter and the 3’-UTR regions. Animal studies showed that high levels of PON1 protect individuals against acute organophosphatespoisoning. The PON1 genotype and enzymatic activity together contribute to determining an individual's PON1 “status”. In this study, the role of PON1 gene polymorphismsand its enzymatic activity was assessed as a prognostic marker in cases of acute poisoning by cholinestersase inhibitor (ChEI) pesticides among a sample of Egyptian population. Two equal groups of 100 unrelated individuals participated in the study: an exposed group and non-exposed group as control. Serum paraoxonase1 enzyme activitymeasured as arylesterase activity spectrophotometrically using the substrate phenyl acetate. PON1 Q192R gene was genotyped using PCR-RFLP technique. The PON1 Q192R genotype frequency distribution in control subjects was (QQ=64%, QR=28%, RR=8%) and in patients was (QQ=54%, QR=42%, RR=4%) and this was statistically significant (p=0.029). The arylesterase activity was significantly higher in control than exposed group (p=0.037). Regarding the effect of Q192R genotype and arylesterase activity on the outcome, there was no significant difference between the good and poor prognosis groups. Evaluation of PON1 status may be important for determining individual susceptibility to poisoning by ChEI pesticides. However, the estimated level of arylesterase after exposure to poisoning can’t be used in prediction of prognosis. Moreover, the coding genes show discrepant results even within the same ethnic group.